IBI 2010 Annual Report by EPFL School of Life Sciences

EPFL School of Life Sciences - 2010 Annual Report

IBI - Institute of Bioengineering The Institute of Bioengineering sits at the interface of the life sciences and of engineering, being situated in both the School of Life Sciences and the School of Engineering and reporting to both deans. This dual affiliation allows great diversity in hiring faculty from different backgrounds and with different research perspectives, all focused on basic biological sciences using quantitative and systems analyses, as well as translating the biological and biochemical sciences into therapeutics and diagnostics. The dual affiliation also provides a rich educational environment, both at the BS/MS and PhD levels, especially since a joint MS program in Bioengineering has come into effect in the fall of 2010, shared between the two Schools. In pursuit of basic biological mechanisms, IBI faculty investigate questions such as: • How the cellular micro-environment controls cellular differentiation and morphogenetic processes; • How stem cell processes, such as self-renewal and differentiation, are determined; How cell migration and trafficking in complex environments is modulated; • How complex biological networks such as metabolism, gene expression and protein trafficking are regulated; and • How biophysical and biomolecular signals interact in controlling cellular behavior.

IBI - Institute of Bioengineering

Our goal is to transform knowledge gained from our studies into clinical applications. To that end, the IBI faculty develop novel technologies in areas including: interventional and diagnostic biomedical micro-devices, synthetic and biosynthetic biomaterials for delivery of small molecule drugs, proteins and DNA, materials in bio-nanotechnology, immunotherapy based on active biomolecules and nanomaterials, novel molecules for photodynamic therapy, and tissue engineering for therapeutics as well as physiological modelling based on biomolecular and stem cell approaches. ‘http://ibi.epfl.ch’

EPFL School of Life Sciences - 2010 Annual Report

Auwerx - Schoonjans Lab http://auwerx-lab.epfl.ch/

IBI

Johan Auwerx and Kristina Schoonjans use a systems physiology approach to understand metabolic homeostasis and the pathogenesis of common metabolic diseases.

Johan Auxerx, MD, PhD Full Professor Nestle Chair in Energy Metabolism

Kristina Schoonjans Professeur Titulaire

Introduction

The research of the Laboratory of Integrative and Systems Physiology (LISP) aims to understand how regulatory proteins, including nuclear receptors, membrane receptors and transcriptional cofactors, act as sensors for molecules of nutritional, metabolic or pharmacological origin, and translate this into altered gene expression and protein patterns affecting metabolic function.

for these common diseases. The importance of these discoveries is testified by the fact that several compounds targeting these receptors and or cofactors have made it into the clinic. Examples of drugs for which our research contributed to clinical development are the fibrates (that target PPARα), thiazolidinediones (that target PPARγ), PPARβ/δ agonists, bile acids and bile acid derivatives (that target both the TGR5 and FXR), and resveratrol and SRT1720 (which activate SIRT1).

Keywords

Diabetes, genetics, metabolism, metabolic disease, phenogenomics, transcription

Results Obtained in 2010

The Auwerx/Schoonjans laboratory was amongst the pioneers to unravel the wide-ranging implications of the three PPARs, PPARα, PPARβ/δ, and PPARγ, in metabolic control. Perhaps most striking in this context was our discovery of an association between the PPARγ Pro12Ala gene variant with type 2 diabetes and obesity, identified long before the era of genome-wide association studies, and as such the first gene tied with these common complex diseases. We established how the enterohepatic nuclear receptors, LRH1 and SHP, govern hepatic lipid and bile acid metabolism, regulate mucosal immune homeostasis, and control fertility via their commanding role on steroid production. We furthermore identified bile acids as endocrine regulators of energy expenditure, through the activation of a novel membrane receptor, TGR5. Finally, We established that transcriptional cofactors, such as the acetyltransferases (SRC2/TIF2 and SRC-3) and the deacetylases (such as SIRT1), fine-tune energy homeostasis by changing the acetylation status of PGC-1α, the master regulator of mitochondria. Since altered signaling by nuclear receptors and cofactors, contributes to the pathogenesis of type 2 diabetes, obesity and atherosclerosis, our research paved the way for novel preventive and therapeutic strategies

EPFL School of Life Sciences - 2010 Annual Report

Selected

Publications

Houtkooper, R.H., Williams, R.W., Auwerx, J. (2010). Metabolic networks of longevity. Cell 142 :9-14. Canto, C., Jiang, L.Q., Desmukh, A.S., Mataki, C., Coste, A., Lagouge, M., Zierath, J., Auwerx, J. (2010). The interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and excercise in skeletal muscle. Cell Metabolism 11:213-219. Thomas, C., Gioiello, A., Noriega, L., Strehle, A., Oury, J., Rizzo, G., Machiarullo, A., Yamamoto, H., Mataki, C. , Pruzanski, M., Pelliciari, R., Auwerx, J., Schoonjans, K. (2009). TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metabolism 10:167-177. Koutnikova, H., Laakso, M., Lu, L., Combe, R., Paananen, J., Kuulasmaa, T., Kuusisto, J., Haring, H.U., Hansen, T., Pedersen, O., Smith, U., Hanefeld, M., Williams, R.W., Auwerx, J. (2009). Identification of the UBP1 locus as a critical blood pressure determinant using a combination of mouse and human genetics. Plos Genetics e1000591. Argmann, C., Dobrin, R., Heikkinen, S., Auburtin, A., Pouilly, L., Cock, T.A., Koutnikova, H., Zhu, J., Schadt, E.E., Auwerx, J. (2009). PPARγ is a key driver of longevity in the mouse. Plos Genetics, e1000752

Team Members

Post doctoral Associates Carles Canto Pablo Fernandez-Marcos Taoufiq Harach Riekelt Houtkooper Ellen Jeninga Chikage Mataki, until Nov ‘10 Laurent Mouchiroud Lilia Noriega Thijs Pols Dongryeol Ryu Raffaele Teperino, until June ‘10 Hiroyasu Yamamoto Jiujiu Yu PhD Students Pénélope Andreux Mitsonura Nomura Evan Williams, from Sept. 2010 Master’s Students Genevieve Rydlo, Evan Williams, until Aug. 2010

Lab Technicians Sabrina Bichet Thibaud Clerc Marie-Laure Dénéreaz, until September 2010 Amandine Moriot-Signorino-Gelo Norman Moullan

Canto, C., Gerhart-Hines, Z., Feige, J.N., Lagouge, M., Noriega, L., Millne, J.C., Puigserver, P., Auwerx, J. (2009). AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 458:1056-1060.

Administrative Assistant Valérie Stengel

Heikkinen, S., Argmann, C., Feige, J.N., Koutnikova, H., Champy, M.F., Dali-Youcef, N., Schadt, E.S., Laakso, M., Auwerx, J. (2009). The Pro12Ala PPARγ2 variant determines metabolism at the gene-environment interface. Cell Metabolism 9:88-98. Duggavathi, R., Volle, D.H., Mataki, C., Antal, M.C., Messadeq, N., Auwerx, J., Murphy, B.D., Schoonjans, K. (2008). Liver receptor homolog 1 is essential for ovulation. Genes Dev. 22:1871-1876.

IBI - Institute of Bioengineering

Feige, J.N., Lagouge, M., Canto, C., Strehle, A., Houten, S., Millne, J., Lambert, P.D., Mataki, C., Elliot, P.J., Auwerx, J. (2008). Specific SIRT activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation. Cell Metabolism 8:347-358.

Mice treated with resveratrol are protected from obesity.

EPFL School of Life Sciences - 2010 Annual Report

Barrandon Lab http://ldcs.epfl.ch/

IBI

Yann Barrandon, MD-PhD, is joint professor in Stem Cell Dynamics at the EPFL and at the Lausanne University (Unil), and head of the Department of Experimental Surgery at the CHUV. He has made major contributions in basic epithelial stem cell biology and in stem cell therapy. Dr Barrandon is a principal investigator in several EEC stem cell consortia (EuroSystem, Optistem and BetacellTherapy).

Yann Barrandon

Full Professor, EPFL / CHUV Head of Experimental Surgery CHUV

Introduction

The goal of the Barrandon laboratory is to understand skin morphogenesis, manipulate stem cell fate and translate stem cells from bench to bedside. The laboratory investigates stem cell fate in skin and other epithelia using single cell analysis and serial transplantation. The research aims 1- at understanding epidermal metaplasia, 2at reconstructing epidermal appendages (hair follicles, sebaceous glands and sweats glands in patients transplanted with autologous epidermal stem cells, 3- at improving engraftment of transplanted epidermal stem cells and 4- at developing ex vivo gene therapy for Recessive Dystrophic Epidermolysis Bullosa, a horrendous hereditary skin disease.

Keywords

Stem cells, metaplasia, micro-environment, skin, thymus, cell and gene therapy

Results Obtained in 2010

Adult (tissue) stem cells are responsible for long-term renewal, regeneration and repair. Hence, they have the capacity to self-renew and to generate a differentiated progeny for an extended period of time (theoretically a lifetime). Human skin is privileged because its stem cells (epithelial and mesenchymal) can be extensively cultured and cloned, genetically manipulated and transplanted. Our current research targets the role of small microenvironmental variations on epidermal stem cell behavior and aims at exploring the potency of p63-expressing epithelial stem cells in stratified epithelia, trachea, bladder and thymus in several species including the human. We have demonstrated that all stratified epithelia of the rat, independent of their primary germ line origin contain clonogenic stem cells that can respond to skin morphogenetic signals by forming epidermis, sebaceous glands and hair follicles, a capacity that is maintained in serial transplantation. On the other hand, p63-expressing cells of the bladder and of the trachea can only form an epidermal like-structure reminiscent of epidermal metaplasia (Claudinot et al., submitted). The thymus contains

epithelial cells (TECs) that form a unique 3D structure that does not resemble that of a simple or stratified epithelium, even if some TECs express markers of skin differentiation (Hassallâ&#x20AC;&#x2122;s bodies). We have demonstrated that the thymus of the rat contains a population of clonogenic p63-expressing TECs with astonishing capabilities. These cells maintain a thymic identity in vitro and express MHC class II and Aire (Autoimmune regulator) when incorporated into a reconstituted thymus in vivo. Surprisingly, these cultured cells can adopt the fate of bona fide multipotent stem cells of the hair follicle when exposed to skin morphogenetic signals, a property maintained in serial transplantation. Gene profiling experiments have demonstrated that several transcription factors important for thymus identity were either down regulated or silenced in TECs recovered from skin. This clearly represents an increase in potency and the demonstration that adult stem/progenitor cells can be robustly reprogrammed by micro-environmental cues (Bonfanti et al., Nature 2010). We are pursuing our investigation to determine the extent of TECs potency. Most importantly, stem/progenitor cells of squamous epithelia are particularly exposed to environmental hazards because of their unique location at the interface of the body with the external world. We have demonstrated that a difference as small as 0.5 degree Celsius, e.g. from 36.5 to 37Â°C, can impact gene expression in cultured human keratinocyte stem/progenitor cells and we have identified mammalian TOR (mTOR) as a transcriptional modulator (Brouard et al., submitted). Our results strongly suggest that stem/progenitor cells can rely on mTOR signaling to balance a changing niche. We are pursuing our investigation to determine the impact of mTOR signaling on cultured human keratinocyte stem/progenitor cells before and after transplantation.

EPFL School of Life Sciences - 2010 Annual Report

Selected

Publications

Bonfanti, P., Claudinot, S., Amici, A.W., Farley, A., Blackburn, C.C, Barrandon, Y. (2010). Microenvironmental reprogramming of thymic epithelial cells to skin multipotent stem cells. Nature 466, 978-982. Gurtner, G. C., Werner, S., Barrandon, Y., Longaker, M. T. (2008). Wound repair and regeneration. Nature 453: 314-21. Majo, F., Rochat, A., Nicolas, M., Abou Jaoudé, G., Barrandon, Y. (2008). Oligopotent stem cells are distributed throughout the ocular surface. Nature 456: 250-254. Epub 2008 Oct 1.

Team Members Senior scientists Brouard Michel Rochat Ariane

Post doctoral fellows Bonfanti Paola Braschler Thomas Caillier-Veron Maia Claudinot Stéphanie Droz-Georget Stéphanie Gonneau Christèle Grasset Nicolas Teisanu Roxana Volorio Christelle PhD Students Amici Alessandro Gorostidi François Maggioni Melissa Mosig Johannes Stolf Daiana Master Student Cohen Lionel Andrey Jérémy Peterman Katrin Scientific Collaborators Bon Anne-Charlotte Graber Julien Clinical Trial Collaborator Savioz-Dayer Emmanuelle Supporting Staff Mercier Louis Vermot Steeve Supporting Staff COP Burki Marko Gomez Luis Da Costa

IBI - Institute of Bioengineering

Administrative Staff Guex Nathalie

Blistering of the skin in a patient suffering from Recessive Dystrophy Epidermolysis Bullosa. Deficient Collagen VII is immunostained in red.

EPFL School of Life Sciences - 2010 Annual Report

Dal Peraro Lab http://lbm.epfl.ch

IBI

Matteo Dal Peraro graduated in Physics at the University of Padua in 2000. He obtained his Ph.D. in Biophysics at the International School for Advanced Studies (SISSA, Trieste) in 2004. He received postdoctoral training at the University of Pennsylvania (Philadelphia) under the guidance of Prof. M. L. Klein. He was nominated Tenure Track Assistant Professor at the EPFL School of Life Sciences in late 2007, where he is heading the Laboratory for Biomolecular Modeling (LBM), within the Interfaculty Institute of Bioengineering (IBI).

Matteo Dal Peraro Tenure-track Assistant Professor

Introduction

We use advanced molecular modeling techniques combined with high-performance computing to investigate biological systems, in particular their function emerging from structure. Our main targets are bacterial and viral systems and their mechanism of resistance towards natural and clinical drugs. We develop new multi scale schemes and models to extend the power of current molecular simulations to tackle problems such as the assembly of large macromolecular complexes and the design of remedies for pathogenic infections.

Keywords

Computational biophysics, biochemistry, and structural biology; bacteria and viruses; multi scale molecular simulations; macromolecular assembly; protein and drug design; high-performance computing

Results Obtained in 2010

In the past decade, the advances of computational structural biology have permitted to extend our knowledge of biological function at the molecular level shedding light on features that are often experimentally inaccessible. During 2010, within this domain we continued focusing on the development of new coarse-grained force fields for molecular simulations of proteins, which can allow a more consistent overlap of quantities derived from the computational and experimental setting. These new models will permit to tackle complex problems such as protein-ligand recognition and protein-protein interactions in large macromolecular networks with unprecedented sampling power and accuracy.

within this framework were functional to define the functional multimeric state of these systems on the basis of available experimental restraints. Of particular interest in 2010, are our findings about the molecular basis of growth control for the type III secretion system used by bacteria to infect host cells. In particular, the needle length of the Yersinia spp. injectisome is known to be determined by YscP, an early substrate of the injectisome itself. There is a linear correlation between the length of YscP and the length of the produced needle, suggesting that YscP acts as a molecular ruler (Mol Microbiol 2009). However, it is not known whether one single molecule of YscP suffices to control the length of one needle or whether several molecules of YscP are exported in alternation with the needle subunit YscF until the needle length matches the ruler length, which would stop needle growth. To address this question a interdisciplinary computational/experimental approach was adopted. Different strains expressing simultaneously a short and a long version of YscP were engineered by our collaborators (Cornelisâ&#x20AC;&#x2122; Lab in Basel) (Figure). The experimentally obtained needle length distribution was compared to the distributions predicted by stochastic modeling of the various possible scenarios of needle growth based on a molecular description of the YscP-needle interactions (Figure). The comparison between predictions and experimental results clearly showed as a single ruler YscP protein controls the needle length and excluded possible mechanisms involving more than one ruler per needle (Figure).

In parallel, we advanced on the structural and dynamical characterization of large macromolecular assembly and function in bacterial nanomachines such as the pore-forming toxin aerolysin from Aeromonas hydrophila (in collaboration with the van der Goot Lab at EPFL), and the PhoQP twocomponent system from E.coli, which is involved in bacterial chemotaxis. Molecular simulations

EPFL School of Life Sciences - 2010 Annual Report

Selected

Publications

Wagner, S., Stenta, M., Metzger, L.C., Dal Peraro M. and Cornelis, G.R. (2010). Length control of the injectisome needle requires only one molecule of Yop secretion protein P (YscP). Proc. Natl. Acad. Sci. USA. 107(31):13860-13865.

Team Members Post doctoral Davide Aleman Marco Stenta

Ho, M.H., De Vivo, M., Dal Peraro, M. and Klein, M.L. (2010). Understanding the Effect of Magnesium Ion Concentration on the Catalytic Activity of Ribonuclease H through Computation: Does a Third Metal Binding Site Modulate Endonuclease Catalysis. J. Am. Chem. Soc. 132:1370213712.

PhD Students Christophe Bovigny Matteo Degiacomi Hassan Pezeshki Thomas Lemmin Enrico Spiga

Khurana, E., Devane, R., Dal Peraro, M. and Klein, M.L. (2010). Computational study of drug binding to the membrane-bound tetrameric M2 peptide bundle from influenza A virus. Biochimica et Biophysica Acta (BBA) – Biomembranes. 1808:530–537.

Adnimistrative Assistant Marie-France Radigois

Alemani, D., Collu, F., Cascella, M. and Dal Peraro, M. (2010). A nonradial coarse-grained potential for proteins produces naturally stable secondary structure elements. Journal of Chemical Theory and Computation. 6(1):315-324. Simona, F., Magistrato, A., Dal Peraro, M., Cavalli, A., Vila, A.J. and Carloni, P. (2009). Common mechanistic features among metallo-β-lactamases: a computational study of Aeromonas hydrophila CphA enzyme. The Journal of biological chemistry. 284(41):28164-28171. Cascella, M. and Dal Peraro, M. (2009). Challenges and perspectives in biomolecular simulations: from atomistic picture to multiscale modeling. CHIMIA International Journal for Chemistry. 63(1-2):14-18. Ho, M.-H., De Vivo, M., Dal Peraro, M. and Klein, M.L. (2009). Unraveling the Catalytic Pathway of Metalloenzyme Farnesyltransferase through QM/MM Computation. Journal of Chemical Theory and Computation. 6:1657-1666 Khurana, E., Dal Peraro, M., DeVane, R.,Vemparala, S., DeGrado, W.F. and Klein, M.L. (2009). Molecular dynamics calculations suggest a conduction mechanism for the M2 proton channel from influenza A virus. Proc. Natl. Acad. Sci. USA 106(4):1069-1074.

IBI - Institute of Bioengineering

Wagner, S., Sorg, I., Degiacomi, M., Journet, L., Dal Peraro, M. and Cornelis, G.R. (2009). The helical content of the YscP molecular ruler determines the length of the Yersinia injectisome. Mol. Microbiol. 71(3):692-701.

On the left, needle length distribution predicted for the single-ruler static model (scenario 1) and the multi-ruler dynamic model (scenarios 2 and 3), when merodiploids express simultaneously a short (yscP388) and a long (yscP686) version of YscP (shown in the box). On the right, comparison between experimental and predicted needle length distributions according to the different scenarios. The single-ruler mechanism of needle length control (schematically reported on top) is the only compatible with experiments. (Adapted from PNAS 2010).

EPFL School of Life Sciences - 2010 Annual Report

Deplancke Lab

http://deplanckelab.epfl.ch/

IBI

Bart Deplancke performed his undergraduate and M.Sc. studies in bio-engineering at Ghent University (Belgium). Afterwards, he pursued his Ph.D. in Immunobiology with Dr. Rex Gaskins in the Division of Nutritional Sciences at the University of Illinois (Urbana-Champaign, USA). As a postdoctoral fellow, he teamed up with Dr. Marian Walhout, first in the laboratory of Dr. Marc Vidal at the DanaFarber Cancer Institute of Harvard Medical School, and later at the University of Massachusetts Medical School where Marian established her own laboratory. At the end of 2007, Bart Deplancke arrived at the EPFL and founded his Laboratory of Systems Biology and Genetics.

Bart Deplancke Tenure-track Assistant Professor

Introduction

Gene regulatory networks control gene expression and therefore play a vital role in metazoan development and function. The LSBG is using highthroughput sequencing, large-scale yeast screens, microfluidics, and computational approaches to characterize the gene regulatory networks underlying differential gene expression in Drosophila and mammals.

Keywords

Systems Biology, Gene Regulatory Network, Transcription, Quantitative Genetics, Mouse, Drosophila, Yeast, Genetic Engineering

Results Obtained in 2010

In 2004, we developed a Gateway-compatible yeast one-hybrid system allowing for the first time the screening of regulatory elements for interacting proteins in straight-forward fashion (Deplancke et al., Genome Res., 2004). This work has since resulted in the publication of several high-profile papers (Cell, Genes Dev., Genome Res., Mol Syst. Biol.), but was until now limited to C. elegans and still suffered from being quite laborious and expensive.

Drosophila TF ORF clone library containing 692 of the 755 (95%) predicted TFs in versatile Gateway Entry format of which the large majority (81%) are fully sequence-verified. This is to our knowledge one of the most comprehensive, sequence-verified TF ORF libraries to date for any metazoan organism and should serve as a highly valuable resource for the Drosophila community at large. Second, our previous work showed that a haploid yeast-based matrix assay is most optimal in terms of overall protein-DNA interaction coverage, but least optimal in terms of time and cost. To pair optimal coverage with highest possible throughput and lower cost, we engineered a novel robotic platform that completely automates and significantly scales down the haploid yeast transformation process (Figure). Third, to significantly fasten the identification of positives and to eliminate the subjective factor of calling positives by eye, we generated a novel image processing program called TIDY (for Transcription factor-DNA Interaction Detection in Yeast). Fourth, we stringently validated this novel platform achieving a conservative detection rate of 26% of literature-reported protein-DNA interactions in line with results of other yeastbased screens, and finally, we found many novel interactions and provide evidence for several of them that they may be biologically relevant.

In parallel with efforts to make this technology available for human and Arabidopsis, the LSBG developed during the last two years an automated platform that enables the high-throughput proteinDNA interaction screening of Drosophila regulatory elements of interest. Because of the availability of a high-quality genome sequence and many genetic tools, Drosophila has one of the best characterized metazoan genomes in terms of functionally annotated regulatory elements. Yet for most of these, it is still not known which TFs are interacting. The ability to screen annotated regulatory elements for interacting TFs should therefore of great value for the Drosophila community. Compared to our original work in 2004, the Drosophila platform features several important advances and novelties. First, we generated a full-length

EPFL School of Life Sciences - 2010 Annual Report

Publications

Massouras, A., Hens, K., Gubelmann, C., Uplekar, S., Decouttere, F., Rougemont, J., Cole, S.T., Deplancke, B. (2010). PrInSeS: Primer-Initiated Sequence Synthesis. Nature Methods. 7:485-6. Massouras, A., Decouttere, F., Hens, K., Deplancke, B. (2010). WebPrInSeS: automated full-length clone sequence identification and verification using high-throughput sequencing data. Nucleic Acids research. 38:W378-842010. Simicevic, J., Deplancke, B. (2010). DNA-centered approaches to characterize regulatory protein-DNA interaction complexes. Molecular Biosystems. 6:462-8, 2010. Deplancke, B. (2009). Experimental advances in the characterization of metazoan gene regulatory networks. Briefings in Functional Genomics and Proteomics. 8:12-27. Reece-Hoyes*, J.S., Deplancke*, B., Barrasa, I., Hatzold, I., Smit, R., Arda, E., Pope, P., Gaudet, J., Conradt, B., Walhout, A.J.M. (2009). The C. elegans Snail homolog CES1 can activate gene expression by binding to an extended binding site, and share targets with bHLH transcription factors, Nucleic Acid Research, 37:3689-3698, 2009.

Team Members

Post-doctoral students Monica Albarca Korneel Hens Sunil Raghav PhD Students Carine Gubelmann Alina Isakova Irina Krier Andreas Massouras Jovan Simicevic Sebastian Waszak Masterâ&#x20AC;&#x2122;s student Manuella Leveque Scientific assistants Jean-Daniel Feuz Antonina Iagovitina Administrative assistant Marie-France Radigois

IBI - Institute of Bioengineering

Selected

The Drosophila high-throughput yeast one-hybrid platform: a yeast DNA bait strain is distributed over a 384-well plate after which yeast in each well of this plate is transformed with a different AD-TF clone from the Drosophila Y1H AD-TF library by a robotic yeast transformation platform which additionally spots the 384 individually transformed yeast strains on a permissive agar plate. A colony pinning robot subsequently transfers the yeast colonies onto a permissive and a selective plate, quadruplicating each colony in a square pattern in the process after which TF- DNA bait interactions can be observed as growth on a selective, 3-AT-containing yeast plate.

EPFL School of Life Sciences - 2010 Annual Report

Hubbell Lab http://lmrp.epfl.ch

IBI

Jeffrey Hubbell was trained as a chemical engineer from Kansas State University (B.S.) and Rice University (Ph.D.) in the United States. Previous to moving to Lausanne, he was on the faculty at the Swiss Federal Institute of Technology Zurich, at the California Institute of Technology, and at the University of Texas in Austin. He is author of more than 250 papers in peer-reviewed journals and inventor on more than 100 patents. He is a member of the National Academy of Engineering, USA

Jeffrey A. Hubbell

Full Professor Director of IBI Merck-Serono Chair in Drug Delivery

Introduction

We design novel materials for investigation of basic cell biological phenomena such as stem cell self-renewal and differentiation and applications in medicine such as drug delivery, regenerative medicine, and vaccination. We focus on examples where novel materials are necessary to solve the problem, thus working at the interface between materials science and biology.

Keywords

Biomaterials, tissue engineering, protein engineering, extracellular matrix, immunobioengineering, vaccines

Results Obtained in 2010

Regenerative medicine: The laboratory made exciting advances in engineering matrix-bound morphogens for conjugation in biomaterial matrices for tissue repair and regeneration. We had previously developed a biochemical approach to incorporate morphogenetic proteins into surgical matrices such as fibrin, two of which have now entered into clinical testing in bone repair and chronic wound healing in more than 500 patients in collaboration with corporate partners. We have further developed this concept, engineering extracellular matrix proteins, based on fibronectin, to comprise a promiscuous growth factor-binding domain proximal to an integrinbinding domain. The growth factor-binding domain was observed to bind to more than 20 growth factors from very diverse families. Synergistic signaling between the bound integrin and the bound growth factor receptor was observed in numerous growth factor receptor systems, and synergistic effects on tissue repair and regeneration were observed with in chronic wound repair, driven by enhanced angiogenesis, and bone repair, driven by enhanced mesenchymal stem cell infiltration, in mouse models. Using such approaches of engineered extracellular matrix protein-based morphogen templating, it was possible to induce tissue morphogenesis much more effectively and at much lower doses than with the free morphogenetic proteins.

and Cancer Bioengineering (Prof. M.A. Swartz), the laboratory demonstrated that nanoparticles can be used as a vaccine platform for targeting cells in the lymph nodes draining dermal site and the lung, in addition to secondary lymphoid tissues in the nasal cavity. This, combined with advanced design of the polymeric nanoparticle surfaces, has enabled a new generation of vaccines, highly stable and very economical, for use in both the developing and the developed world. The team has demonstrated that ultra-small particles, smaller than biological particles, can be swept into the lymphatics within a few minutes of injection, drain to the lymph nodes, and are collected there for antigen presentation. Particularly favorable antigen conjugation schemes were developed for promotion of MHC I presentation and induction of potent CD8+ T cell responses, very impressive protection of mice versus influenza and Mycobacterium tuberculosis challenge was demonstrated, much more impressive than with free antigen delivered with the same adjuvants. From a materials perspective, our focus is on self-assembling block copolymers that form polymer micelles, upon the surface of which antigens are conjugated, or polymer vesicles, in the core of which antigens are encapsulated. Given that our interest is in inducing cellular immunity for chronic disease, our materials are designed to enhance mechanisms of antigen cross-presentation. In addition to inducing cellular immunity, we are also keenly interested in polymeric vaccine forms to tolerize versus cellular immunity, harnessing the tolerogenic antigen presentation that occurs with antigen from apoptotic cells yet using simple biomolecular and polymer conjugate forms that are clinically tractable.

Vaccines and immunotherapeutics: In collaboration with the Laboratory for Lymphatic

EPFL School of Life Sciences - 2010 Annual Report

Selected

Publications

van der Vlies AJ, O’Neil CP, Hasegawa U, Hammond N, & Hubbell JA (2010) Synthesis of pyridyl disulfide-functionalized nanoparticles for conjugating thiol-containing small molecules, peptides, and proteins. Bioconj. Chem. 21(4):653-662. Patterson J & Hubbell JA (2010) Enhanced proteolytic degradation of molecularly engineered PEG hydrogels in response to MMP-1 and MMP-2. Biomaterials 31(30):7836-7845. Lee ST, Yun JI, Jo YS, Mochizuki M, van der Vlies AJ, Kontos S, Ihm JE, Lim JM, & Hubbell JA (2010) Engineering integrin signaling for promoting embryonic stem cell self-renewal in a precisely defined niche. Biomaterials 31(6):1219-1226. Hirosue S, Kourtis IC, van der Vlies AJ, Hubbell JA, & Swartz MA (2010) Antigen delivery to dendritic cells by poly(propylene sulfide) nanoparticles with disulfide conjugated peptides: Cross-presentation and T cell activation. Vaccine 28(50):7897-7906. Martino MM, Mochizuki M, Rothenfluh DA, Rempel SA, Hubbell JA, & Barker TH (2009) Controlling integrin specificity and stem cell differentiation in 2D and 3D environments through regulation of fibronectin domain stability. Biomaterials 30(6):1089-1097. Jo YS, van der Vlies AJ, Gantz J, Thacher TN, Antonijevic S, Cavadini S, Demurtas D, Stergiopulos N, & Hubbell JA (2009) Micelles for Delivery of Nitric Oxide. J. Am. Chem. Soc. 131(40):14413-14418. Hubbell JA, Thomas SN, & Swartz MA (2009) Materials engineering for immunomodulation. Nature 462(7272):449-460. Arrighi I, Mark S, Alvisi M, von Rechenberg B, Hubbell JA, & Schense JC (2009) Bone healing induced by local delivery of an engineered parathyroid hormone prodrug. Biomaterials 30(9):1763-1771.

Team Members Post-doctoral fellows De LaPorte Laura Dane Karen Engelhardt, Eva-Maria Hasegawa Urara Lee Seung Tae Mochizuki Mayumi Nembrini Chiara O’Neil Conlin Patterson Jennifer Rice Jeffrey Scott Evan Tomei Alice Tortelli Federico Van der Vlies André Velluto Diana Yun JungIm PhD students Ahmadloo Hamideh Ciapala Karine De Titta Alexandre Eby Jackson Kontos Stephane Kourtis Iraklis Larsson Hans Mattias Lorentz Kristen Mahou Redouan Martino Mikaël Micol Lionel Pisarek Rubin Berek Raghunathan Sandeep Schütz Catherine Stano Armando Yang Lirong Master students Julier Ziad Leonidova Anna Metzger Stephanie Taghavi Shadi Vocat Véronique Bachelor students Saint Auguste Pamela Vonerlach Thibaud Zerdani Jalil

Other scientific personnel Frey Peter, Adj. Prof. Wandrey Christine, Teaching and Research Master Simeoni Eleonora,Scientist Dessibourg Céline, Sci. Assist. Quaglia Xavier, Lab Assist. Pasquier Miriell, Lab Assist. Administrative Assistant Bonzon Carol Anne

A critical-size bone defect in the calvarium of the rat was used to evaluate bone repair in response to BMP-2 and PDGF-BB co-delivered with an engineered fibronectin fragment (left) or free (right). Clearly, engineering the extracellular milieu enhanced growth factor efficacy.

IBI - Institute of Bioengineering

Internships Diplas Bill Ferreira Daniela Hopkins Amy Wanakule Prinda

EPFL School of Life Sciences - 2010 Annual Report

Lutolf Lab http://lscb.epfl.ch

IBI

Dr. Matthias Lutolf was trained as a Materials Engineer at ETHZ where he also carried out his Ph.D. studies on the development of a novel class of biomolecular materials for tissue engineering (awarded with ETH medal, 2004). In 2005, Lutolf joined the Baxter Laboratory in Stem Cell Biology at Stanford University to work on hematopoietic stem cells; research sponsored by SNSF and Leukemia and Lymphoma Society fellowships. In 2007 Lutolf won a European Young Investigator (EURYI) award to start up his independent research at EPFL.

Matthias P. Lutolf Tenure-track Assistant Professor

Introduction

Stem cells can hardly be grown in a culture dish (‘ex vivo’), posing a substantial hurdle for their clinical use. We develop and apply innovative bioengineering tools that allow studying and controlling stem cell behavior in a rationale fashion. These technologies have the potential to be translated into clinical settings, for example to expand rare hematopoietic stem cells to treat blood cancers.

Keywords

Stem cells, self-renewal, single cell analysis, niche, hydrogel engineering, microfluidics

Results Obtained in 2010

A complex mixture of extracellular cues delivered by support cells is critical for adult stem cell maintenance and the regulation of self-renewal in their micro-environment, termed niche. Despite recent progress in the identification of relevant niche proteins and signaling pathways in mice, to date, many adult stem cell populations cannot be efficiently cultured in vitro without rapidly differentiating. To address this important issue, we have developed novel stem cell culture technologies that allow fate changes of individual stem cells to be monitored in vitro, under near-physiologic conditions and in real time. These artificial niches were fabricated from ‘smart’ poly(ethylene glycol) (PEG) hydrogels that allow key biochemical characteristics of adult stem cell niches to be mimicked and the physiological niche complexity deconstructed into a smaller, experimentally amenable number of distinct signaling interactions. Moreover, because many adult stem cell populations are inherently heterogeneous and current stateof-the-art culture techniques do not permit efficient dynamic analyses of fates of large numbers of single cells, 2D and 3D hydrogel patterning techniques were developed that allow to confine and microarray single stem cells for high-throughput experimentation. In order to mimic cell-cell interactions typical of niches without the complexity of co-culture, we have for example invented protein micropatterning methods for hydrogels allowing to expose confined stem cells to teth-

ered protein cues, singly or in combination, or to overlapping protein gradients. These artificial niches have been utilized to explore the fate of individual mouse hematopoietic stem cells (HSC), neural stem cells and muscle satellite cells. For example, time-lapse microscopy of several thousand single HSC cultured in micro-well arrays over several days, combined with subsequent image analyses allowed growth kinetics of selected populations to be statistically analyzed. Retrospective transplantation experiments in mice were performed in order to correlate proliferation kinetics with self-renewal function. A pronounced difference in cell division kinetics, that is predictive of their in vivo blood reconstitution potential, was observed when we compared the behavior of standard multipotent progenitors with long-term repopulating HSC. Furthermore, microfluidic chip technology was developed to sequentially capture single HSC after multiple divisions (see figure) to assess their fate for example by multigene single cell qRT-PCR. Ongoing experiments are geared towards the identification of the role of niche factors in directing the symmetry of stem cell divisions. Our efforts to systematically ‘deconstruct’ stem cell niches may serve as a broadly applicable paradigm for defining and reconstructing artificial niches to accelerate the transition of stem cell biology to the clinic.

EPFL School of Life Sciences - 2010 Annual Report

Selected

Publications

Gilbert PM, Havenstrite KL, Sacco A, Leonardi N, Peggy Kraft, Nguyen NK, Lutolf MP, and Blau HM (2010). Matrix rigidity regulates skeletal muscle stem cell self-renewal in culture, Science, 329 (5995): 1078 – 1081 Mosiewicz, K., Johnsson, K. and Lutolf, M.P. (2010). Phosphopantetheinyl Transferase-Catalyzed Formation of Bioactive Hydrogels for Tissue Engineering, J.Am.Chem.Soc., 132 (17): 5972–5974 Kobel, S. and Lutolf, M.P.(2010). High-throughput methods to define complex stem cell niches, Biotechniques, 48 (4) ix–xxii Kobel, S., Valero, A., Latt, J. Renaud, P., and Lutolf, M.P. (2010). Optimization of microfluidic single cell trapping for long-term on-chip culture, Lab Chip, 10: 857 - 863 Lutolf, M.P.*, Gilbert, P.M., Blau, H.M.* (2009). Designing materials to direct stem cell fate, Nature, 462: 433-441 Cosson, S., Kobel, S., Lutolf, M.P. (2009). Biomolecule gradients on synthetic hydrogels, Advanced Functional Materials, 19(21): 3411-3419

Team Members Post doctoral Samy Gobaa Marta Roccio Nicola Vannini Olaia Naveiras (20%) PhD Students Simone Allazetta Steffen Cosson Mukul Girotra Sylke Hoehnel Stefan Kobel Katarzyna Mosiewicz Andrea Negro Yuya Okawa Adrian Ranga Aline Roch Master Students Colette Bichsel Tanja Hausherr Viktoria Stepanova Administrative Assistant Saira Banu Mohamed-Kanani

Kobel, M., Limacher, M., Gobaa, S. Lutolf, M.P. (2009). Soft embossing of hydrogels, Langmuir, 25 (15): 8774–8779

IBI - Institute of Bioengineering

Jo Y.S., Gantz, F., Hubbell, J.A., Lutolf, M.P. (2009), Tailoring hydrogel degradation and drug release via neighboring amino acid-controlled ester hydrolysis, Soft Matter, 5: 440-446

(A) Microfluidic device for following progeny deriving from single HSC (note dime for size comparison). On one chip, 256 parental HSC can be spatially trapped and pedigree tracked over up to 4 divisions (16 traps per column). The entire chip is constantly perfused to replenish cell culture media, change micro-environmental conditions or perform other analyses (e.g. immunostaining). (B) Self-regulating (fluidic) cell trapping principle. (C) Optimized single cell trapping efficiency (close to 100%). (D) Successful re-trapping of daughter cell generated by division of a single HSC.

EPFL School of Life Sciences - 2010 Annual Report

Naef Lab

http://naef-lab.epfl.ch/

IBI

Felix Naef studied theoretical physics at the ETHZ and obtained his PhD from the EPFL in 2000. He received postdoctoral training at the Center for Studies in Physics and Biology at the Rockefeller University (NYC). His research focuses on the study of biomolecular oscillators, modeling, and transcription regulation. He was nominated Tenure Track Assistant Professor at the EPFL School of Life Sciences in 2005. He is currently a member of the Institute of Bioengineering (IBI)

Felix Naef

Tenure-track Assistant Professor

Introduction

Our lab is interested in quantitative and systems biology. We work on various problems including circadian biology, developmental patterning, transcription regulatory networks, and single cell imaging. To study these systems we apply theoretical, computational and experimental methods.

Keywords

Circadian transcription, chronobiology, circadian clocks precision, fluctuations and bursting in gene expression spatio-temporal model of patterning in the early Drosophila embryo

Results Obtained in 2010

Circadian gene regulation: Temporal mapping of BMAL1 binding sites in mouse liver reveals genome-wide daily rhythms in DNAbinding and uncovers output functions controlled by the circadian oscillator. The circadian clock is a timing system that allows organisms to keep behavioral, physiological, and cellular rhythms in resonance with daily environmental cycles. In mammals, such clocks use transcriptional regulatory loops in which the heterodimeric transcription factor BMAL1/CLOCK plays a central role. While defects in the circadian clock function have been associated with diabetes, obesity or cancer, the molecular links between the circadian clock and output pathways are poorly characterized. Here, we mapped DNA-binding sites of BMAL1 in mouse liver during one circadian cycle. Our temporal analysis revealed widespread daily rhythms in DNA-binding with maximum levels peaked at midday, with strongest sites found mainly at core circadian genes. Interestingly, BMAL1 targets were highly enriched for genes involved in carbohydrate and lipid metabolism, but also for transcription factors, in particular nuclear receptors. Our results suggest that the mammalian clock uses BMAL1 to control both directly and indirectly transcriptional output programs. DNA specificity of BMAL1 binding revealed the importance of tandem E-box elements, which may favor strong binding and precise timing

of daily gene expression. Taken together, our work strengthens BMAL1â&#x20AC;&#x2122;s primary function as master regulator of the core circadian oscillator, while contributing in a more distributed fashion to a variety of output programs. A 3D model of the developing Drosophila embryo. The early patterning of the Drosophila embryo is one of the most advanced models for systems biology approaches. For years, dynamical models for the gap gene network have been calibrated from spatio-temporal expression patterns. These models are usually restricted to a one-dimensional segment running anterior-posterior (A-P) on the side of the embryo. Recently, experimental progress provided mRNA and protein expression atlases (cf. The Berkeley Drosophila Transcription Network Project) measured on the whole surface of the syncytium (Figure). This now opens the possibility to model the early segmentation process on the real geometry of the embryo. Unlike previous models, we explicitly model mRNA and proteins, which is important due to delays in the accumulation of the regulators. Our best-fit network clearly indicates the importance of nonlinear regulation by Hunchback. In addition, we validated our model by comparing predictions with mutant data for the gap genes and bicoid dosage mutants showing shifts in the domains of the gap genes. We not only demonstrate that modeling segmentation in fly embryos is now realistic on the embryo surface, but also show that it can uncover novel features of the gap gene network. Taken together, we believe that whole organism scale, data driven modeling, opens new avenues for systems biology of development.

EPFL School of Life Sciences - 2010 Annual Report

Selected

Publications

Blanchoud, S., Budirahardja, Y., Naef*, F., Gonczy*, P., «ASSET: a robust algorithm for the automated segmentation and standardization of early Caenorhabditis elegans embryos», Dev Dyn 239, 3285 (2010). *corresponding authors. Stoll, G., Bischofberger, M., Rougemont, J., Naef, F., «Stabilizing patterning in the Drosophila segment polarity network by selecting models in silico», Biosystems 102, 3 (2010). Preti, M., Ribeyre, C., Pascali, C., Bosio, M. C., Cortelazzi, B., Rougemont, J., Guarnera, E., Naef, F., Shore, D., Dieci, G., «The telomere-binding protein Tbf1 demarcates snoRNA gene promoters in Saccharomyces cerevisiae», Mol Cell 38, 614 (2010). Parisi, F., Sonderegger, B., Wirapati, P., Delorenzi, M., Naef, F., «Relationship between estrogen receptor alpha location and gene induction reveals the importance of downstream sites and cofactors», BMC Genomics 10, 381 (2009). Parisi, F., Koeppl, H., Naef, F., «Network inference by combining biologically motivated regulatory constraints with penalized regression», Ann N Y Acad Sci 1158, 114 (2009).

Team Members Post doctoral Teresa Ferraro Nacho Molina Bhaswar Ghosh

PhD Students Mirko Bischofberger (jointly with Gisou van der Goot) Guillaume Rey Thomas d’Eysmond Simon Blanchoud (jointly with Pierre Gönczy) Jonathan Bieler Laura Symul Julia Cajan Johannes Becker Benjamin Zoller Internship Students Johannes Becker (until June 2010) Julia Cajan (until July 2010) Administrative Assistant Sophie Aquilar

Hazen, S. P., Naef, F., Quisel, T., Gendron, J. M., Chen, H., Ecker, J. R., Borevitz, J. O., Kay, S. A., «Exploring the transcriptional landscape of plant circadian rhythms using genome tiling arrays», Genome Biol 10, R17 (2009). Dibner, C., Sage, D., Unser, M., Bauer, C., d’Eysmond, T., Naef, F., Schibler, U., «Circadian gene expression is resilient to large fluctuations in overall transcription rates», EMBO J 28, 123 (2009).

IBI - Institute of Bioengineering

Benazet, J. D., Bischofberger, M., Tiecke, E., Goncalves, A., Martin, J. F., Zuniga, A., Naef, F., Zeller, R., «A self-regulatory system of interlinked signaling feedback loops controls mouse limb patterning», Science 323, 1050 (2009).

The expression data for the gap genes at stage C14, i.e. after 14 nuclear divisions. Left to right : hb, Kr, gt ,kni,; top row is the mRNA, bottom row the proteins. These data serve as input to our extended model.

EPFL School of Life Sciences - 2010 Annual Report

Swartz Lab

http://swartz-lab.epfl.ch

IBI

Melody Swartz received her BS and PhD in Chemical Engineering from Johns Hopkins University and M.I.T., respectively. Following a postdoc at Harvard, she became an Assistant Professor at Northwestern University in Biomedical Engineering. She has been at the EPFL in the Institute of Bioengineering since 2003 and was appointed full professor in 2010. She has joint appointments in the ISREC and ISIC (Institute of Chemistry and Chemical Engineering, part of the School of Basic Sciences).

Melody A. Swartz Full Professor

Introduction

The lymphatic system is an important regulator of fluid balance, innate immunity and peripheral tolerance. We are fascinated by this network of vessels that drain fluid, antigens, and cells from the periphery, through the lymph nodes, and back into the blood. By uncovering its complex roles in immunity and tolerance, we hope to understand – and ultimately manipulate – its participation in cancer progression and metastasis.

Keywords

Lymphatic, lymph node, immunity, tolerance, tumor, metastasis, interstitial flow, mechanobiology

Results Obtained in 2010

In 2010, we contributed new fundamental understanding of the lymphatic micro-environment in immunity and cancer, and of how dendritic cells (DCs) interpret different types of cues in this complex biomechanical environment. We also contributed to the mechanobiology of lymphatic endothelium, demonstrating the importance of flow on lymphatic function as well as on tumor cell migration in the lymphatic micro-environment. DC homing to lymphatic vessels and positioning within the lymph node is regulated by gradients of the CCR7 ligands CCL21 and CCL19; however, it was unclear how DCs interpret gradients of these competing chemokines in complex 3D environments. Using a novel 3D chemotaxis chamber in which stable, well-defined gradients can be rapidly established, we demonstrated that DCs differentially respond to CCL21 and CCL19, which lead to different receptor recycling kinetics, and can respond to gradients as small as 0.4% (Haessler et al, PNAS, in press). These data represent the first quantitative analysis of DC chemotaxis in 3D environments.

mor margin – which express lymphoid stromal-like characteristics driven to CCL21 secretion – the overall result was more of an immune suppressive, and tolerogenic, response compared to tumors with knocked-down CCL21. These data suggest that tumor CCL21 can help direct the education of naïve T cells within the tumor margin, along with regulatory T cells, leading to immune escape. With regards to interstitial flow mechanobiology, we introduced a new mechanism of interstitial flow as a modulator of tumor cell migration in the tumor micro-environment, specifically by modulating TGF-β release from the matrix and the subsequent cross-talk between stromal fibroblasts (seen in the tumor periphery) and cancer cells, which follow migrating fibroblasts in the tumor margin (Shieh et al, Cancer Res, 2011). We also found that transmural flow directly activates lymphatic endothelial cells, modulating their chemokine and adhesion molecule expression that in turn promoted DC transmigration into lymphatic vessels (Miteva et al, Circ Res, 2010). We also continued to develop and characterize lymph node-targeting nanoparticles for immunomodulation in collaboration with Jeffrey Hubbell’s lab. Specifically, we characterized the uptake, processing, and presentation of antigen delivered by nanoparticles to dendritic cells (Hirosue et al, Vaccine, 2010), the control of complement deposition according to surface chemistry (Thomas et al, Biomaterials, 2010), and demonstrated its potential in mucosal vaccination and ability to enhance adjuvant effects (Stano et al, Vaccine, 2010).

In the context of solid tumors, we had previously shown that CCL21 was secreted by a number of invasive tumor cells (Shields et al, Cancer Cell, 2007), and we explored the implications of this on host immune response to the tumor, since CCL21 would attract various types of immune cells as occurs in the lymph node. We discovered that CCL21 secretion by tumors helps promote immunological tolerance (Shields et al, Science, 2010). By attracting dendritic cells and T cells to the tu-

EPFL School of Life Sciences - 2010 Annual Report

Selected

Publications

Haessler, U., Pisano, M., Wu, M., and Swartz, M.A. Dendritic cell chemotaxis in 3D under defined chemokine gradients reveals differential response to CCL21 and CCL19. Proc. Natl. Acad. Sci. U.S.A. (in press) Shieh, A.C., Rozansky, H.A., Hinz, B., and Swartz, M.A. (2011). Tumor cell invasion is promoted by interstitial flow-induced matrix priming by stromal fibroblasts. Cancer Res. 71(3):790-800.

Team Members Post doctoral Sachiko Hirosue Witold Kilarski Amanda Lund Evan Scott Adrian Shieh Jacqui Shields Jeremy Teo Susan N. Thomas

Hirosue, S. Kourtis, I.C., Van der Vlies, A.J., Hubbell, J.A.*, and Swartz, M.A.* (2010). Antigen delivery to dendritic cells by poly (propylene sulfide) nanoparticles with disulfide conjugated peptides: Cross-presentation and T cell activation. Vaccine 28:7897-7906.

PhD Students Marie Ballester Alexandre de Titta Esra Guç Laura Jeanbart Ulrike Haessler Iraklis Kourtis Marco Pisano Sandeep Raghunathan Valentina Triacca

Lund, A.W. and Swartz, M.A. (2010). Role of lymphatic vessels in tumor immunity: Passive conduits or active participants? J Mammary Gland Biol Neoplasia 15(3):341-52.

Visiting scholars Vidya Raghavan (Fulbright Fellow) Vanessa Kennedy (Whitaker Fellow)

Shields, J.D., I.C. Kourtis, Tomei, A.A., Roberts, J., and Swartz, M.A. (2010). Induction of lymphoid-like stroma and immune escape by tumors that express the chemokine CCL21. Science. 328(5979):749-52. (comment: “Perspectives,” Science 328:697-7, 2010; “Research Highlights,” Nature Rev. Cancer, 10(5):292, 2010).

Master’s Students Marcela Rincon Ristrepo Efthymia Vokali

Thomas, S.N.,Van der Vlies, A.J., O’Neil, C.P., Yu, S.S., Giorgio, T.D., Swartz, M.A.*, and Hubbell, J.A.* (2011). Engineering complement activation on polypropylene sulfide vaccine nanoparticles. Biomaterials 32(8):2194-203.

Administrative Assistant Ingrid Margot

Miteva, D.O., Dixon, J.B., Kilarski, W., Rutkowski, J.M., Shields, J.D., and Swartz, M.A. (2010). Transmural flow modulates cell and fluid transport functions of lymphatic endothelium: A potential early cue for inflammation. Circ. Res. 106(5):920-31. Hubbell, J.A.*, Thomas, S.N., and Swartz, M.A.* (2009). Materials engineering for immunomodulation. Nature 462(7272):449-460. Pedersen, J.A., Lichter, S., and Swartz, M.A. (2010). Cells in 3D matrices under interstitial flow: Effects of pericellular matrix alignment on cell shear stress and drag forces. J. Biomech. 43:900-905. Rutkowski, J.M., Markhus, C.E. Gyenge, C.C., Alitalo, K., Wiig, H. and Swartz, M.A. (2010). Dermal collagen and fat accumulation correlate with tissue swelling and hydraulic conductivity in murine lymphedema. Am J Pathol. 176(3):1122-9.

IBI - Institute of Bioengineering

Tomei, A.A., Siegert, S., Britschgi, M.R., Luther, S.A., and Swartz, M.A. (2009). Fluid flow regulates stromal cell organization and CCL21 expression in a tissue-engineered lymph node model. J Immunol 183(7):4273-83. Issa, A., TX Le, AN Shoushtari, Shields, J.D., and Swartz, M.A. (2009). VEGF-C and CCL21 in tumor cell – lymphatic crosstalk promote invasive phenotype. Cancer Res. 69:349357.

Activated antigen-presenting cells (White, MHCII) are seen interacting with lymphatic (green, LYVE-1) and blood capillaries (red, CD31) in mouse skin after exposure to inflammatory stimulus. Type IV collagen (blue) surrounds both as well as adipocytes and nerves. Photo credit: Dr. Witek Kilarski

EPFL School of Life Sciences - 2010 Annual Report

Wurm Lab

http://lbtc.epfl.ch

IBI

Florian M. Wurm: PhD, 1979 Genetics, University of Giessen, Germany. After having worked for 5 years at Hoechst AG in Marburg, Florian joined Harvard Medical School. In 1986 he joined Genentech Inc., San Francisco, holding leading positions in Process Sciences. Since 1995 he has taken a Professorship in Biotechnology at the EPFL, and he was appointed Visiting Professor at Jinan University in Guangzhou, China in 2008. He has published more than 180 scientific papers and holds more than 10 patents. He is founder and CSO of ExcellGene SA, in Monthey, Switzerland.

Florian M. Wurm Full Professor

Introduction

Mammalian cells are now considered the most versatile and productive system for the manufacture of recombinant proteins for pharmaceutical applications. The major goal of the Laboratory of Cellular Biotechnology is the development of novel and/ or improved tools for gene transfer to cultured mammalian cells and subsequent high-level expression of recombinant proteins from such cells in innovative and scalable production systems (bioreactors).

Keywords

Recombinant protein expression - Mammalian cell culture – Bioreactor – Bioprocess control – Gene transfer - DNA integration - Microinjection - Stable cell line development – Orbital shaking

Results Obtained in 2010

Research at the LBTC is situated on the crossroads between biology and engineering, and it addresses the expression of recombinant proteins from suspension cultures of mammalian cells, which is the major approach to therapeutic protein production. We are investigating two major thematic areas: (1) gene delivery and transient gene expression in animal cells and their respective impacts on the host cells physiology and genetics (2) orbital shaking technology and novel bioreactor systems. The main results obtained in 2010 are summarized below.

integration. Understanding transgene integration at the molecular level will allow us to develop strategies to prevent the widely observed phenomenon of gene silencing, which lowers productivity in cell clones over time. Lentiviral vectors and transposon (integrase) mediated DNA delivery is hoped to improve the integration of DNA into the actively transcribed chromatin of the host cells genome. In 2010 we succeeded in generating high producing, stable CHO cell lines by lentivirusmediated gene transfer. The orbitally shaken (OS) bioreactor technology for mammalian cell cultivation, designed in our lab, has been scaled-up to 1’000 L. Orbitally shaken cylindrical vessels (with nominal volumes from 50 mL to 250 L) are being extensively studied in order to characterize the hydrodynamics of this type of agitated systems. A scale-up factor for the OS bioreactors could be determined by mixing time analysis in small scale experiments. In collaborations with Prof. Alfio Quarteroni (Chair of Modelling and Scientific Computing) and Dr. Mohamed Farhat of the Laboratory of Hydraulic Machines, a fluid dynamics model of the OS bioreactor could be determined and tested. Overall, our research provided useful insights for understanding cell cultivation in suspension, gene integration and protein expression. These studies are of general interest in cellular biology and biotechnology.

Transient gene expression (TGE) and stable transgene integration. TGE allows to express a fully glycosylated recombinant protein at very high titers (1 g/L for IgGs) in HEK-293 cells only 2-3 weeks after gene cloning. We have studied the cellular uptake and disassembly of PEI-DNA complexes in mammalian cells and we combined with this, our knowledge of the cellular metabolism of cells in batch cultures in bioreactors. To study stable integration of recombinant genes into the genome of a host cell we have focused on the Chinese hamster ovary cell line (CHO), which is the most widely used cell line in the biotech industry. We have investigated the cytogenetics of CHO-derived stable cell lines generated using different DNA delivery techniques, including transposon-mediated and lentivirus-mediated gene

EPFL School of Life Sciences - 2010 Annual Report

Publications

Oberbek A, Matasci M, Hacker DL, Wurm FM. (2010) Generation of stable, high-producing CHO cell lines by lentiviral vector-mediated gene transfer in serum-free suspension culture. Biotechnol Bioeng 108(3): 600-10. Wulhfard S, Baldi L, Hacker DL, Wurm F. (2010) Valproic acid enhances recombinant mRNA and protein levels in transiently transfected Chinese hamster ovary cells. J Biotechnol 148(2-3): 128-32. Zhang XW, Garcia IF, Baldi L, Hacker DL, Wurm FM. (2010). Hyperosmolarity enhances transient recombinant protein yield in Chinese hamster ovary cells. Biotechnol Lett 32(11): 1587-1592. Tissot S, Farhat M, Hacker DL, Anderlei T, Kühner M, Comninellis C, Wurm F. (2010). Determination of a scaleup factor from mixing time studies in orbitally shaken bioreactors. Biochem Eng J 52(2-3): 181-186. Engelhardt, E. M., E. Stegberg, R. A. Brown, et al. (2010). Compressed collagen get: a novel scaffold for human bladder cells. Journal of Tissue Engineering and Regenerative Medicine 4(2): 123-130. Hacker, D. L., M. De Jesus and F. M. Wurm (2009). 25 years of recombinant proteins from reactor-grown cells - Where do we go from here? Biotechnol Adv. 27: 1023–1027. Zhang X, Stettler M, De Sanctis D, Perrone M, Parolini N, Discacciati M, De Jesus M, Hacker D, Quarteroni A, Wurm F. (2009) Use of orbital shaken disposable bioreactors for Mammalian cell cultures from the milliliter-scale to the 1,000-liter scale. Adv Biochem Eng Biotechnol 115: 33-53. Nallet S, Amacker M, Westerfeld N, Baldi L, König I, Hacker DL, Zaborosch C, Zurbriggen R, Wurm FM. (2009). Respiratory syncytial virus subunit vaccine based on a recombinant fusion protein expressed transiently in mammalian cells. Vaccine 27(46): 6415-9. Engelhardt EM, Houis S, Gries T, Hilborn J, Adam M, Wurm FM. (2009). Suspension-adapted Chinese hamster ovaryderived cells expressing green fluorescent protein as a screening tool for biomaterials. Biotechnol Lett 31(8): 1143-9.

Team Members

Post Doctoral Scientists Lucia Baldi Unser David Hacker Mattia Matasci Patrick Olavi Michel Sévérine Petitprez Qiuling Xie PhD Students Zuzana Kadlecova Divor Kiseljak Sagar Shashidhar Manoli Dominique T. Monteil Sophie Nallet Agata Oberbek Yashas Rajendra Xiao Shen Stéphanie Tissot Francesca Zagari Master Students Riad Gacem Guillaume Lüthi Joao N. Dos Santos Pereira Sowmya Balasubramanian External PhD Students Fatemeh Davami Trainees Jérémy Baras Clara J. Douet Sarah Grezet Sébastien Noll Amélie Thomas Technical Assistants Virginie Bachmann Ione Gutscher Broccard Gilles Administrative Assistant Fabienne Rudin

IBI - Institute of Bioengineering

Selected

Metaphase and nuclei of lentivirus infected CHO cells. Metaphasic chromosomes and nuclei are DAPI stained. Integration sites are visualized by using Fluorescence in situ hybridization (FISH).

EPFL School of Life Sciences - 2010 Annual Report

Aminian Lab -

coaffiliated STI

http://lmam.epfl.ch/

IBI

Kamiar Aminian is currently Professor of medical instrumentation and he is teaching in the area of electronics, sensors and instrumentation, medical devices, biomechanics, and sports. He is the inventor of Physilog® system for movement analysis and owner of 5 patents (or patent pending) in the field of movement analysis based on inertial sensors and author of more than 300 publications in international journals, conference proceedings and book chapter. He received the 2008 Venel Award of Swiss Society of Orthopedics for his contribution to functional evaluation of shoulder pathologies by means of a new wearable system.

Kamiar Aminian Adjunct Professor School of Engineering

Research Interests

The multidisciplinary research of the Laboratory of Movement Analysis and Measurement aims to transfer bioengineering findings into clinical applications. We are particularly interested to characterize sport performances and pathologies affecting motor function such as osteoarthritis, frailty, pain or movement disorder by studying the movement ability. Our research involves biomechanical instrumentation for measuring and modeling human biodynamics in daily conditions, during spontaneous activity or physical exercises. Based on body worn sensors, we design wearable systems and algorithms for long-term monitoring of physical activity and gait analysis, for the estimation of the 3D joint kinematics and kinetics, and for the sport performance evaluation. Based on these features and instruments new metrics are defined and validated to provide early diagnosis and objective clinimetry for outcome evaluation in orthopedics and aging, to assess the change of motor function with disease and rehabilitation, to characterize improved performances in sport, and to classify movement disorders.

Selected

Publications

Mariani, B., Hoskovec, C., Rochat, S., Bula, C., Penders, J., and Aminian, K. (2010). 3D gait assessment in young and elderly subjects using foot-worn inertial sensors, Journal of Biomechanics, 43 (15): 2999 – 3006. Rouhani, H., Favre, J., Crevoisier, X. and Aminian, K. (2010). Ambulatory Assessment of 3D Ground Reaction Force using Plantar Pressure Distribution, Gait & Posture, 32(3): 311-316. Favre J., Crevoisier X., Jolles B.M. and Aminian K. (2010). Evaluation of a mixed approach combining stationary and wearable systems to monitor gait over long distance, Journal of Biomechanics , 43(11): 2196–2202. Salarian A., Horak F., Zampieri C., Carlson-Kuhta P., Nutt J. and Aminian K. (2010). iTUG, a Sensitive and Reliable Measure of Mobility, IEEE Transactions on Neural Systems & Rehabilitation Engineering, 18 (3), 303-310. Allet L., Armand S., Aminian K., Pataky Z., Golay A., de Bie R. and de Bruin E. (2010). An exercise intervention to improve diabetic patients’ gait in a real-life environment, Gait & Posture 32(2): 185-190.

Seematter-Bagnoud, L., Santos-Eggimann, B., Rochat, S., Martin, E., Karmaniola, A., Aminian, K., Piot-Ziegler, C. and Büla, C.J. (2010). Vulnerability in high-functioning persons aged 65 to 70 years: the importance of the fear factor, Aging Clinical and Experimental Research 22(3): 212-218 Rochat, S., Büla, C.J., Martin, E., Seematter-Bagnoud, L., Karmaniola, A., Aminian, K., Piot-Ziegler, C. and Santos-Eggimann, B.S. (2010). What is the relationship between fear of falling and gait in well-functioning older persons aged 65 to 70 years? Archives of Physical Medicine and Rehabilitation, 91(6): 879-884.

Team Members Scientist Hooman Dejnabadi Anisoara Ionescu Postdoc Hossein Rouhani PhD Students Arash Arami Arnaud Barré Julien Chardonnens Farzin Dadashi Cyntia Duc Raluca Ganea Benoît Mariani Scientific assistant Fabian Massé Technician Pascal Morel Jean Gramige Administration assistant Danielle Alvarez Master’s Students Francois Curdy Alicia Garrido Mathhieu Hayoz Samuel Marclay

EPFL School of Life Sciences - 2010 Annual Report

Fantner Lab -

coaffiliated STI

http://lbni.epfl.ch/ Georg Fantner is an assistant professor for bio- and nanoinstrumentation in the Interfaculty Institute of Bioengineering (IBI), with affiliation in the department of science and technology (STI). His research focusses on developing and using novel nanoscale characterization methods to answer questions in life science, with a specific interest in cell membranes and protein-membrane interactions. Prof. Fantner has a strong background in atomic force microscopy, biomaterials and microfabrication. He received his Bs and Ms from the Technical University Graz, his PhD from the University of California Santa Barbara and did a post doc in the biomolecular materials lab at the Massachusetts Institute of Technology. Georg Fantner Tenure-track Assistant Professor School of Engineering

Research Interests

Our research aims to advance nanoscale measurement technology for life science applications, with a special focus on high speed Atomic Force Microscopy. Using this novel technique, we study the structure of cell membranes and lipid model membrane system with nanometer resolution and two orders of magnitude faster than previously possible. The high spatial and high temporal resolution allows us to study how membrane disrupting toxins, such as antimicrobial peptides, pore forming proteins or antimicrobial polymers interact with the membrane. Other research interests are the dynamics of lipid patch organization, molecular interactions in organic/inorganic nanocomposites such as bone, and protein induced mineralization. On the technology development side, we work on the integration of high speed AFM with fluorescence microscopy, micro- and nano-fluidics for sample handling and NEMS cantilever design.

Selected

Publications

Fantner, G. E., Schumann, W., Barbero, R. J., Deutschinger, A., Todorov, V., Gray, D. S., Belcher, A. M., Rangelow, I. W., Youcef-Toumi, K. (2009). Use of self-actuating and self-sensing cantilevers for imaging biological samples in fluid. Nanotechnology, 20 (43), Fantner, G. E., Burns, D. J., Belcher, A. M., Rangelow, I. W., Youcef-Toumi , K. (2009). DMCMN: In Depth Characterization and Control of AFM Cantilevers With Integrated Sensing and Actuation. J Dyn Syst-T Asme, 131 (6), -

Team Members Post doctoral Jonathan Adams Blake Erickson

Master’s Students Benea-Chelmus Ileana-Cristina ADministrative Assistant Tamina Sissoko

IBI - Co-affiliated Research Groups

Nam, Y. S., Shin, T., Park, H., Magyar, A. P., Choi, K., Fantner, G., Nelson, K. A., Belcher, A. M. (2010). VirusTemplated Assembly of Porphyrins into Light-Harvesting Nanoantennae (2010). J Am Chem Soc, 132 (5), 1462Fantner, G. E., Barbero, R. J., Gray, D. S., Belcher, A. M.(2010). Kinetics of antimicrobial peptide activity measured on individual bacterial cells using high-speed atomic force microscopy. Nat Nanotechnology, 5 (4), 280285 Hansma, P., Turner, P., Drake, B., Yurtsev, E., Proctor, A., Mathews, P., Lulejian, J., Randall, C., Adams, J., Jungmann, R., Garza-de-Leon, F., Fantner, G., Mkrtchyan, H., Pontin, M., Weaver, A., Brown, M. B., Sahar, N., Rossello, R., Kohn, D. (2009) The bone diagnostic instrument II: Indentation distance increase. Rev Sci Instrum, 80 (6), -

EPFL School of Life Sciences - 2010 Annual Report

Guiducci Lab

- coaffiliated STI

http://clse.epfl.ch

IBI

Carlotta Guiducci holds her PhD in Electrical Engineering from the University of Bologna (I). She was a postdoc at the Nanobiophysics Lab at Ecole Supérieure de Physique et Chimie Industrielles Paris (F) between 2005 and 2007. Later at University of Bologna she led a joint research group of electrical engineers, physicists and biologists funded by an EU IP (DiNamICS). In 2009, She joined the Institute of Bioengineering at the Swiss Federal Institute of Technology in Lausanne (CH) where she holds a position as Tenure-Track Assistant Professor.

Carlotta Guiducci

Tenure-track Assistant Professor Swiss Up Engineering Chair School of Engineering

Research Interests

The Laboratory of Life Sciences Electronics aims at (i) developing and characterizing integrable sensing techniques for sensing bimolecular events and interacting with living matter, (ii) contributing to the development of 3D compatible novel microfabrication technologies for the implementation of biochips. Detection and quantification of very small amounts of biological species are the common issues of fundamental areas of health-care and life sciences, ranging from early detection of diseases to the development of personalized medicine. CLSE focus on applications such as point-of-care solutions for therapeutic drug monitoring and on the interactions between amyloids and lipid bilayers membranes. CLSE employs widely electrode-based sensing coupled with electrochemical and impedance techniques in fields such as high-throughput integrated biomolecular sensing, flow cytometry, neural recording. Among other techniques under investigation, silicon nanowires (SiNWs) have showed the potential to become a general platform for ultrasensitive label-free detection of biological and chemical species in multisensing applications. CLSE also investigates integrable optical detection techniques such as transmission surface plasmon resonance.

Selected

Guiducci, C., Temiz, Y., Leblebici, Y., Accastelli, E., Ferretti, A., Cappi, G., and Bianchi, E. (2010). Integrating Bio-sensing Functions on CMOS Chips, Proc. of Asia Pacific Conference on Circuits and Systems, Kuala Lumpur, Malaysia, December 6 – 9, 2010. Cagnin, S., Caraballo, M., Guiducci, C., Martini, P., Ross, M., SantaAna, M., Danley, D., West, T., and Lanfranchi, G. (2009). Overview of Electrochemical DNA Biosensors: New Approaches to Detect the Expression of Life, Sensors, 9(4): 3122–3148

Team Members Post doctoral Fabio Mario Spiga PhD Students Enrico Accastelli Giulia Cappi Anna Ferretti Yuksel Temiz Interships Samuel Kilchenmann Angélique Umuhire Master’s Students Valeiria Davì, Enrica Rollo Marco Spinsanti Administrative Assistant Homeira Salimi

Publications

Bianchi, E., Boschetti, F., Dubini, G., and Guiducci, C. (2010). Model of an Interdigitated Microsensor to Detect and Quantify Cells Flowing in a Test Chamber. Proc. of the 6th annual COMSOL Conference, Paris, France, November 17-19 2010. Temiz, Y., Ferretti, A., Accastelli, E., Leblebici, Y., and Guiducci, C. (2010). Robust Microelectrodes Developed for Improved Stability in Electrochemical Characterization of Biomolecular Layers . Proc. of the 9th Annual IEEE Sensors Conference (Sensors’10), pages 1051-1055, Hawaii, USA, November 1-4, 2010.

EPFL School of Life Sciences - 2010 Annual Report

Hatzimanikatis Lab -

coaffiliated SB

http://lcsb.epfl.ch

Associate Professor School of Basic Sciences

Research Interests

Computational biotechnology focuses on the development of mathematical models and systems engineering frameworks for accelerating the design and purposeful manipulation of complex cellular processes. The Laboratory of Computational Systems Biotechnology (LCSB) develops expertise in the formulation of mathematical models of cellular processes and in the development of process systems engineering methods for the integration and analysis of experimental information from different levels. However, most of this information is partial and it is subject to uncertainty. Researchers in LCSB develop methods that can account quantitatively for the uncertainty in the available information and can provide guidance on solving problems in biotechnology and medicine. LCSB is one of the leading laboratories in the study of energetics and thermodynamics of complex cellular processes. Research in LCSB has also pioneered the development of computational methods for the discovery of novel metabolic pathways for metabolic engineering and synthetic biology. The applications areas of research in LCSB are: metabolic engineering and metabolic diseases, bioenergetics, protein synthesis, lipidomics, and drug discovery for infectious diseases.

Selected

Publications

“Thermodynamic Calculations for Biochemical Transport and Reaction Processes in Metabolic Networks”, Stefan J. Jol, Anne Kuemmel, Vassily Hatzimanikatis, Daniel A. Beard, and Matthias Heinemann, Biophysical J., 99 (10), 31393144 (2010). “DREAMS of metabolism”, Keng Cher Soh and Vassily Hatzimanikatis, Trends in Biotech., 28 (10), 501-508 (2010). “Production of biofuels and biochemical: in need of an ORACLE”, Ljubisa Miskovic and Vassily Hatzimanikatis, Trends in Biotech., 28 (8), 391-397 (2010).

“In silico feasibility of novel biodegradation pathways for 1,2,4-trichlorobenzene”, Stacey D. Finley, Linda J. Broadbelt, Vassily Hatzimanikatis, BMC Systems Biology, 4:7, doi:10.1186/1752-0509-4-7 (2010). “The Origins of Time-Delay in Template Biopolymerization Processes”, Luis Mier-y-Teran, Mary Silber, Vassily Hatzimanikatis, PLoS Computational Biology, Apr 1;6(4):e1000726 (2010). “Discovery and analysis of novel metabolic pathways for the biosynthesis of industrial chemicals: 3-hydroxypropanoate”, Christopher S. Henry, Linda J. Broadbelt, Vassily Hatzimanikatis, Biotechnology and Bioengineering, 106(3), 462-473 (2010). “Computational framework for predictive biodegradation”, Stacey D. Finley, Linda J. Broadbelt, and Vassily Hatzimanikatis, Biotechnology and Bioengineering, 104 (6), 1086-1097 (2009).

Team members Research Associates Ljubisa Miskovic

IBI - Co-affiliated Research Groups

Vassily Hatzimanikatis

Dr. Vassily Hatzimanikatis received his PhD (1996) and MS (1994) in Chemical Engineering from the California Institute of Technology, and his Diploma (1991) in Chemical Engineering from the University of Patras, Greece. Positions held: Group leader (ETH Zurich); Research Scientist (DuPont), Senior Scientist (Cargill); Assistant Professor (Northwestern University). Vassily has written over 70 technical publications and he is co-inventor in three patents and patent applications. He is associate editor of the journals Biotechnology & Bioengineering, Metabolic Engineering, and Biotechnology Journal. He serves on the editorial advisory board of four biotechnology journals. Honors and Awards: Fellow of the American Institute for Medical & Biological Engineering (2010); DuPont Young Professor (2001-2003); the Jay Bailey Young Investigator Award in Metabolic Engineering (2002); the ACS Gaden Award (2011).

Postdoctoral fellows Ho Ki Fung Georgios Savoglidis Marianne Seijo Katerina Zisaki PhD students Mahdi Alemohammad Stefano Andreozzi James Clulow Noushin Hadadi Andrijana Radivojevic Bachelor/Master Students Pascal Sutter Administrative Assistant Christine Kupper

“Network thermodynamics in the post-genomic era”, Keng Cher Soh and Vassily Hatzimanikatis, Curr. Opin. Microbiol., 13 (3), 350-357 (2010).

EPFL School of Life Sciences - 2010 Annual Report

Ijspeert Lab -

coaffiliated STI

http://biorob.epfl.ch/

Auke Ijspeert Associate Professor School of Engineering

Auke Ijspeert is an associate professor at the EPFL in the Institute of Bioengineering, and head of the Biorobotics Laboratory. He is also Adjunct faculty at the Department of Computer Science at the University of Southern California. He received his engineering degree in physics from the EPFL, and did his PhD in artificial intelligence at the University of Edinburgh. With his colleagues, Dr Ijspeert has received the Best Paper Award at ICRA2002, the Industrial Robot Highly Commended Award at CLAWAR2005, and the Best Paper Award at the IEEE-RAS Humanoids 2007 conference. He was the Technical Program Chair of 5 international conferences (BioADIT2004, SAB2004, AMAM2005, BioADIT2006, LATSIS2006), and has been a program committee member of over 40 conferences. Prof. Ijspeert is also an associate editor for the IEEE Transactions on Robotics.

Research Interests

Our research is at the intersection of robotics and computational neuroscience. It addresses the topics of movement control, sensorimotor coordination, and learning in autonomous robots with multiple degrees of freedom (from snake robots to quadruped robots to humanoid robots). Our ambition is two-fold: (1) to program and design robots that exhibit motor skills with the same efficiency, adaptivity, and robustness as animals, and (2) to get a better understanding of the functioning of animals using numerical simulation and robots as scientific tools. Together with neurobiologists (Jean-Marie Cabelguen and Sten Grillner), we have developed mathematical models of the neural circuits controlling locomotion in lower vertebrates. We have demonstrated how a primitive neural circuit for swimming like the one found in the lamprey can be extended by phylogenetically more recent limb oscillatory centers to explain the ability of salamanders to switch between swimming and walking. These models have been tested in an innovative salamander-like robot capable of swimming and walking. We also develop a dynamical systems approach for controlling movements in robots. For instance, we designed the concept of dynamical movement primitives: nonlinear dynamical systems with well-defined attractor properties that can learn demonstrated discrete or rhythmic movements. Our methods are applied to various robots (quadruped, humanoid and reconfigurable modular robots) and more recently to lower limb exoskeletons for patients with locomotor deficiencies.

Selected

Publications

D. Ryczko, V. Charrier, A. Ijspeert and J.-M. Cabelguen. Segmental Oscillators in Axial Motor Circuits of the Salamander: Distribution and Bursting Mechanisms, Journal of Neurophysiology, vol. 104, p. 2677-2692, 2010.

Ijspeert A.J., Central pattern generators for locomotion control in animals and robots: a review. Neural Networks, 21(4):642-653, 2008 Buchli J., Righetti L., and Ijspeert A.J.. Frequency Analysis with a Nonlinear Dynamical System, Physica D, 237: 1705–1718, 2008. Sproewitz A., Moeckel R., Maye J., Ijspeert A.J., Learning to move in modular robots using central pattern generators and online optimization. International Journal of Robotics Research. 27(3-4):423-443, 2008 Crespi A. and Ijspeert A.J.. Online optimization of swimming and crawling in an amphibious snake robot. IEEE Transactions on Robotics, 24(1), 2008 pp 75-87. Ijspeert A.J., Crespi A., Ryczko D., and Cabelguen J.M.. From swimming to walking with a salamander robot driven by a spinal cord model. Science, 315(5817):1416-1420, 2007.

Team Members

Postdoctoral Researcher Crespi, Alessandro Möckel, Rico Morel, Yannick Spröwitz, Alexander PhD Studnets Ajallooeian, Mostafa Bicanski, Andrej Bonardi, Stéphane Dégallier, Sarah Gay, Sébastien Karakasiliotis, Konstantinos Knüsel, Jérémie Pouya, Soha Tuleu, Alexandre van den Kieboom, Jesse Vespignani, Massimo Administrative Assistant Fiaux, Sylvie

S. Dégallier and A. Ijspeert. Modeling Discrete and Rhythmic Movements through Motor Primitives: A Review, Biological Cybernetics, vol. 103, num. 4, p. 319-338, 2010. A. Spröwitz, S. Pouya, S. Bonardi, J. van den Kieboom, R. Möckel, A. Billard, P. Dillenbourg, A.J. Ijspeert. Roombots: Reconfigurable Robots for Adaptive Furniture, IEEE Computational Intelligence Magazine, 5(3): 20-32, 2010

IBI

EPFL School of Life Sciences - 2010 Annual Report

Johnsson Lab

- coaffiliated SB

http://isic.epfl.ch/lip

Kai Johnsson is currently full professor at the Institute of Chemical Sciences and Engineering at the EPFL. His research interests are the development of chemical approaches to study and manipulate protein function in living cells. He is Associate Editor of ACS Chemical Biology since 2005. He is member of editorial advisory boards of Science, Chemistry&Biology, and Chemical Society Reviews. The protein labeling technologies developed in his laboratory are now available through New England BioLabs.

Kai Johnnson Full Professor School of Basic Sciences

The visualization and characterization of biologically relevant molecules and activities inside living cells continues to transform cell biology into a truly quantitative science. However, despite the spectacular achievements in some areas of cell biology, the majority of cellular processes still operate invisibly. Further progress will therefore depend increasingly on the development of new (fluorescent) sensors and chemical probes to target and characterize these activities. Our research addresses this need by developing and applying chemical approaches to observe and manipulate protein function in living cells. For example, we have introduced general methods for the covalent and specific labeling of fusion proteins with chemically diverse compounds that open up new ways of studying proteins (i.e. SNAP-tag, CLIP-tag and ACP-tag). We are pursuing the further development of such approaches and their application to biological problems that cannot be resolved by traditional approaches.

Selected

Publications

Claudia Trefzer, Monica Rengifo-Gonzalez, Marlon J. Hinner, Patricia Schneider, Vadim Makarov, Stewart T. Cole, Kai Johnsson, “Benzothiazinones are prodrugs that covalently modify the decaprenylphosphoryl-ß-D-ribose 2’-epimerase DprE1 of Mycobacterium tuberculosis” J. Am. Chem. Soc., 132,13663-5 (2010)

proteins based on self-labeling protein tags”, J. Am. Chem. Soc., 131, 5873-84 (2009) Michael Bannwarth, Ivan R. Corrêa Jr, Monika Sztretye, Sandrine Pouvreau, Cindy Fellay, Annina Aebischer, Leandro Royer, Eduardo Ríos, Kai Johnsson, “Indo-1 derivatives for local calcium sensing” ACS Chemical Biology, 4, 179-190 (2009)

Team Members

Postdocs Hirohito Haruki Grazvydas Lukinavicius Damien Maurel Simone Moser Luc Reymond Kui Thong Tan PhD Students Matthias Brun Christopher Chidley Rudolf Griss Birgit Mollwitz Miriam Gronlund Pedersen Albert Schena

IBI - Co-affiliated Research Groups

Research Interests

Administrative Assistant Marie-Claude Gasparini

Mako Kamiya, Kai Johnsson, “A Targetable and Highly Sensitive Calcium Indicator based on BODIPY-fluorophore” Analytical Chemistry, 82, 6472-9 (2010) Damien Maurel, Sambashiva Banala, Thierry Laroche, Kai Johnsson, “Photoactivatable and photoconvertible fluorescent probes for protein labeling” ACS Chemical Biology 5, 507-16 (2010) Arnaud Gautier, Eiji Nakata, Grazvydas Lukinavičius, KuiThong Tan, Kai Johnsson, “Selective crosslinking of interacting proteins using self-labeling tags” J. Am. Chem. Soc. 131, 17954-62 (2009) Matthias A. Brun, Kui-Thong Tan, Eiji Nakata, Marlon J. Hinner, Kai Johnsson “Semisynthetic fluorescent sensor

EPFL School of Life Sciences - 2010 Annual Report

Jolles-Haeberli Lab http://cbt.epfl.ch

Brigitte Jolles-Haeberli Adjunct Professor School of Engineering Director of CBT

Prof. B. Haeberli-Jolles graduated from the EPFL with a MSc Diploma of Professional Engineer in Microtechnology in 1990. In 1995 she obtained her MD, Swiss Federal Diploma of Medicine and her Doctoral thesis in Medicine with honors (UNIL). She then received the Diploma in Clinical Epidemiology in 2002 and successfully completed a Clinical Fellowship in Arthritis Surgery at the University of Toronto. She obtained also the FMH and Swiss Federal Diploma of Specialist in Orthopaedic Surgery and Traumatology. She was nominated Master of Teaching and Research (MER) in 2003 and in 2005, Assistant Professor (PD) at UNIL. In 2008 she was nominated Adjunct Professor (EPFL) where she heads the Interinstitutional Center of Translational Biomechanics (CBT). Dr Jolles-Haeberli was nominated Associate Professor (UNIL) in 2010 where she is the Team leader for Knee and Hip Arthroplasty Surgery (CHUV-UNIL).

Research Interests

We promote and support the transfer of findings from the basic science laboratory to clinical application with a strong relationship between clinicians and engineers for each specific project. Our team develops medical devices and wearable systems to characterize human mobility and locomotion in daily conditions. Based on these instruments, we provide objective clinical metrics for diagnosis and outcome evaluation of treatments as well as useful parameters to increase sport performances. We also carry out work in tissue engineering of musculoskeletal tissues, implant and joints biomechanics, drug delivery systems and mechanobiology. A combination of biomechanical and biological approaches is used to describe and understand different clinical problems of interest such as bone loss following total joint arthroplasty, arthritis or intervertebral disc degeneration. Based on these analyses, original solutions are developed such as fetal cell therapy, scaffolds with high mechanical properties or orthopaedic implants used as drug delivery systems.

Selected

Favre J, Aissaoui R, Jolles BM, De Guise JA, Aminian K. Functional calibration methods for 3D joint angles measurement using inertial sensors: Application to the knee joint. J Biomech 2009; 42(14):2330-5. Biau DJ, Jolles BM, Porcher R. P Value and the Theory of Hypothesis Testing: An Explanation for New Researchers. Clin Orthop Relat Res 2010; 468(3): 885-92. Favre J, Crevoisier X, Jolles BM, Aminian K. Evaluation of a mixed approach combining stationary and wearable systems to monitor gait over long distance. J Biomech. 2010; 43(11): 2196-202.

Center Groups

LBO Lab LMAM Lab for Orthopaedic & sport medicine activities

Administrative Assistant Sabrina Martone

Publications

Gremion G, Gaillard D, Leyvraz PF, Jolles BM. Effect of biomagnetic therapy system on gonathrosis: a double-blind randomised study. J Rehab Med 2009; 41(13): 1090-5. Delaunay C, Epinette JA, Dawson J, Murray D, Jolles BM. Cross-cultural adaptations of the Oxford-12 HIP score to the French speaking population. Orthop Traumatol Surg Res 2009; 95(2): 89-99. Kruger S, Zambelli PY, Leyvraz PF, Jolles BM. Computerassisted placement technique in hip resurfacing arthroplasty: improvement in accuracy? Int Orthop 2009; 33: 27â&#x20AC;&#x201C;33. Coley B, Jolles BM, Farron A, Aminian K. Detection of the movement of the humerus during daily activity. Med Biol Eng Comp 2009; 47: 467-474.

IBI

- coaffiliated STI

EPFL School of Life Sciences - 2010 Annual Report

Maerkl Lab

- coaffiliated STI

http://lbnc.epfl.ch Prof. Maerkl received two bachelor degrees, one in biology and one in chemistry, from Fairleigh-Dickinson University in New Jersey, USA. He then joined the California Institute of Technology, Biochemistry and Molecular Biophysics Option as a graduate student where he worked in the laboratory of Prof. Stephen Quake. After completing his PhD in 2008 he accepted a tenure track position in the Institute of Bioengineering at the EPFL. Prof. Maerkl is currently the lead PI of the DynamiX SystemsX.ch RTD. Prof. Maerkl coaches the EPFL iGEM team and teaches the course Genome & Network Architecture.

Sebastian Maerkl Tenure Track Assistant Professor School of Engineering

In January of 2008 Prof. Maerkl established the Laboratory of Biological Network Characterization (LBNC) at the EPFL. The LBNC is principally interested in developing highly integrated microfluidic devices and applying these to pertinent problems in biology. Of particular interest to the lab are systems biology and synthetic biology, which will benefit tremendously from the development of novel, high-throughput technologies. We are actively developing methods for single cell analysis in S.cerevisiae and S.pombe, as well as M.smegmatis in collaboration with the McKinney Lab (SV/GHI). Using these methods we are interested in characterizing global protein expression dynamics on the single cell level (S.cerevisiae), understand how genotypic variants affect fitness (S.pombe), and discover leads towards understanding and possibly counteracting bacterial persistence (M.smegmatis). The lab is also interested in understanding transcriptional regulatory networks by developing and characterizing promoter variants in vivo, as well as through the biophysical characterization of transcription factors in vitro. We are additionally interested in synthetic biology, for which we are developing novel microfluidic methods.

Selected

Publications

He B., Holloway A., Maerkl S.J., and Kreitman M. (2011). “Does positive selection drive transcription factor binding site turnover? A test with Drosophila cis-regulatory modules.” PLOS Genetics 7(4): e1002053.

Maerkl, S.J. (2009). “Integration column: Microfluidic high-throughput screening.” Integrative Biology 1(1): 1929. Huang, L., S. J. Maerkl and Martin O.J.F. (2009). “Integration of plasmonic trapping in a microfluidic environment.” Optics Express 17(8): 6018-6024. Gerber, D., S. J. Maerkl and Quake S.R. (2009). “An in vitro microfluidic approach to generating protein-interaction networks.” Nature Methods 6(1): 71-4.

Team Members

Post-doctoral Luis Miguel Fidalgo Jose Garcia-Cordero Marcel Geertz (Shore lab U. Geneva) PhD Students Matthew Blackburn Nicolas Denervaud Henrike Niederholtmeyer Jean-Bernard Nobs Arun Rajkumar Sylvie Rockel

IBI - Co-affiliated Research Groups

Research Interests

Master’s Students Valoise Mendoh Mangoua Administrative Assistant Helen Chong

Fidalgo L.M., and Maerkl S.J. (2011). “A software-programmable microfluidic device for automated biology.” Lab on a Chip 11: 1612-19. Geertz M., and Maerkl S.J. (2010). “Experimental strategies for studying transcription factor-DNA binding specificities.” Briefings in Functional Genomics doi:10.1093/ bfgp/elq023. Maerkl S.J. (2010). “Next generation microfluidic platforms for high-throughput protein biochemistry.” Current Opinion in Biotechnology 22(1): 59-65. Maerkl, S.J. and Quake S.R. (2009). “Experimental Determination of the evolvability of a transcription factor.” PNAS 106(44): 18650-5.

EPFL School of Life Sciences - 2010 Annual Report

Mermod Lab -

coaffiliated IBI/UNIL

http://www.unil.ch/biotech

Nicolas Mermod

IBI

Nic Mermod did his PhD on bacterial gene regulation and environmental biotechnology with Ken Timmis at the University of Geneva. As a postdoc with Bob Tjian at the University of California at Berkeley, he identified and characterized some of the first mammalian transcription factors. He then joined the University of Lausanne as an assistant Professor fellow of the Swiss National Science Foundation, to become full professor and director of the Institute of Biotechnology. Nic heads a laboratory at the Center for Biotechnology at EPFL, with an affiliation to IBI. He is also co-founder of Selexis SA, a biotechnology company developing therapeutic-producing cell lines. His research bridges fundamental work on genomics and epigenetics to molecular biotechnology with a therapeutic focus.

Full Professor IBI-UNIL

Research Interests

Our research can be summarized in four main areas: •

Genetic regulation by cell growth factors and tissue regeneration http:// www.unil.ch/Jahia/site/biotech/pid/37429

•

Expression of genes of biotechnological interest in mammalian cells http:// www.unil.ch/Jahia/site/biotech/pid/37430

•

Characterization and modeling of genomic and epigenetic regulators http:// www.unil.ch/Jahia/site/biotech/pid/38548

•

Development of more efficient and safer gene therapy vectors http:// www.unil.ch/Jahia/site/biotech/pid/37432

Selected

Publications

Plasari G, Edelmann S, Hogger F, Dusserre Y, Mermod N and Calabrese A. (2010) Nuclear Factor I-C regulates TGFbeta-dependent hair follicle cycling. J. Biol. Chem., 285: 34115–34125. Puttini S, Lekka M, Dorchies OM, Saugy D, Incitti T, Ruegg UT, Bozzoni I, Kulik AJ, and Mermod N (2009). Gene-mediated restoration of normal myofiber elasticity in dystrophic muscles. Molec. Therapy, 17:19-25. Galbete JL, Buceta M., and Mermod N. (2009) Matrix Attachment Regions regulate the probability of epigenetic switching between active and inactive gene expression. Molec. Biosystems, 5:143-150. Fournier T, Gabriel J-P, Mazza C, Pasquier J, Galbete J and Mermod N. (2009). Stochastic models and numerical algorithms for a class of regulatory networks. Bull. Math. Biol., 71:1394-1431. Esnault G, Majocchi S, Martinet D, Besuchet-Schmutz N, Beckmann JS, and Mermod N. (2009). Transcription factor CTF1 acts as a chromatin domain boundary protein that shields human telomeric genes from silencing. Molec. Cell. Biol. 29:2409-2418.

Kerschgens J, Egener-Kuhn T, and Mermod N. (2009) Protein-binding microarrays: probing disease makers at the interface of proteomics and genomics. Trends Molec. Med., 15:352-358. Plasari G, Calabrese A, Dusserre Y, Gronostajski RM, McNair A, Michalik L, and Mermod N. (2009). Nuclear Factor I-C links PDGF and TGF-beta1 signaling to skin wound healing progression. Molec. Cell. Biol. 29:6006-6017.

Team Members

Laboratory Assistants & apprentice: Alessia Cochard Yves Dusserre Jacqueline Masternak Technical staff : Ione Gutscher Daniel Peter Armindo Teixeira Maître assistant : Nicolas Niederländer Post Doctoral and fellows: Junhua Qiao Niamh Harraghy Stéphanie Renaud Matthieu Delanoy PhD students : Simone Edelmann Kaja Kostyrko Déborah Ley Stefano Majocchi Iaroslav Shcherba Ruthger Van Zwieten Administrative Assistant Ms Nassim Berberat

EPFL School of Life Sciences - 2010 Annual Report

Millán Lab

- coaffiliated STI

http://cnbi.epfl.ch/ José del R. Millán explores the use of brain signals for multimodal interaction and, in particular, the development of brain-controlled robots and neuroprostheses. In this multidisciplinary research effort, Dr. Millán is bringing together his pioneering work on the two fields of brain-machine interfaces (BMI) and adaptive intelligent robotics. He received his Ph.D. in computer science from the Univ. Politècnica de Catalunya (Barcelona, Spain) in 1992. Among other honors, his research on BMI was nominated finalist of the European Descartes Prize 2001 and he has been named Research Leader 2004 by the journal Scientific American for his work on brain-controlled robots.

José del Rocio Millán Associate Professor Defitech Professor School of Engineering

The Defitech Foundation Chair in Non-Invasive BrainMachine Interface (CNBI) carries out research on the direct use of human brain signals for controlling devices and interacting with the environment. In this multidisciplinary research, CNBI is bringing together its pioneering work in the two fields of brain-machine interfaces and adaptive intelligent robotics. A brain-machine interface (BMI) monitors a subject’s brain activity, extracts specific features from the brain signals that reflect his/her intent, and translates these features into actions —such as moving a wheelchair or selecting a letter from a virtual keyboard, without use of muscles or peripheral nerves. CNBI focuses on non-invasive methods for recording brain activity, in particular using electroencephalographic (EEG) signals recorded from electrodes placed on the scalp. The goal of CNBI is to develop principled methods to design intelligent brain-actuated devices that people can efficiently operate them in a natural and intuitive manner over long periods of time. Such neuroprosthetic devices allow interaction by exploiting brain signals associated to different aspects of voluntary behavior.

Selected

Publications

Millán, J. del R., Rupp, R., Müller-Putz, G., MurraySmith, R., Giugliemma, C., Tangermann, M., Vidaurre, C., Cincotti, F., Kübler, A., Leeb, R., Neuper, C., Müller, K.R. and Mattia, D. (2010). Combining Brain-Computer Interfaces and Assistive Technologies: State-of-the-Art and Challenges. Frontiers Neurosci., 4:161. doi:10.3389/ fnins.2010.00161 Chavarriaga, R. and Millán, J. del R. (2010). Learning from EEG Error-related Potentials in Non-Invasive BrainComputer Interfaces. IEEE Trans. Neural Sys. Rehabil. Eng., 18(4):381–388.

Millán, J. del R., Ferrez, P.W., and Seidl, T. (2009). Validation of Brain-Machine Interfaces during Parabolic Flight. Int. Rev. Neurobiol., 86: 189–197. Garipelli, G., Chavarriaga, R., and Millán, J. del R. (2009). Fast Recognition of Anticipation Related Potentials. IEEE Trans. Biomed. Eng., 56(4): 1257–1260.

Team Members Senior Post doctoral Ricardo Chavarriaga Post doctoral Tom Carlson Sarah Degallier Robert Leeb PhD Students Andrea Biasiucci Nicolas Bourdaud Gangadhar Garipelli Zahra Khaliliardali Mohit K. Goel Eileen Y.L. Lew Serafeim Perdikis Sareh Saeidi Hesam Sagha Michele Tavella Luca Tonin Marija Uscumlic

IBI - Co-affiliated Research Groups

Research Interests

Research Assistants Benjamin Hamner Guillaume Monnard Administrative Assistant Eva Gasser

Perrin, X., Chavarriaga, R., Colas, F., Siegwart, R., and Millán, J. del R. (2010). Brain-coupled Interaction for Semi-autonomous Navigation of an Assistive Robot. Robot. Auton. Syst., 58(12): 1246–1255. Millán, J. del R. and Carmena, J. (2010). Invasive or Noninvasive: Understanding Brain-Machine Interface Technology. IEEE Eng. Med. Biol. Mag., 29(1):16–22.

EPFL School of Life Sciences - 2010 Annual Report

Pioletti Lab

- coaffiliated STI

http://lbo.epfl.ch

IBI

Dominique Pioletti received his Master in Physics and PhD in biomechanics from the EPFL. He did then a post-doc at UCSD studying cell/implant interaction. Since April 2006, Dominique Pioletti was appointed Assistant Professor tenure-track at the EPFL and is director of the Laboratory of Biomechanical Orthopedics. His research topics are focusing on biomechanical aspects in the understanding of mechano-transduction in bone, in the development of orthopedic implant as drug delivery system, and in the tissue engineering of bone.

Dominique P. Pioletti Tenure Track Assistant Professor School of Engineering

Research Interests

The projects developed at the LBO are at different levels from basic to applied researches with an overall strategy to bring the developed research to clinical application, the so-called translational research. The core aspect is to use and develop biomechanical descriptions to understand or develop new strategies in the field of musculo-skeletal system. In particular, our projects are organized in four categories: mechano-transduction, tissue engineering, biomechanics of joints and implants, and drug delivery system. A particularity of the LBO is to involve surgeons in most of the developed projects, allowing us to obtain a more effective way for the translational aspect of our research. Translation also means valorization, so we still continued our long lasting collaborations with several industries such Tornier, Stryker or Symbios. In particular, we also obtained financial support from the KTI to develop new solutions in orthopedic implants with some of these companies.

Selected

Publications

tion of cancellous bone screws can compensate for the absence of cortical fixation. J Biomechanics 43:2869-2874. Quintin, A., Schizas, C., Scaletta, C., Jaccoud, S., Applegate, L.A., Pioletti, D.P. (2010) Plasticity of fetal cartilaginous cells. Cell Transplantation 19:1346-1357.

Team Members

Group leaders Prof. Lee A. Laurent-Applegate Dr. Alexandre Terrier Post-doctoral fellows Dr. Nathalie Krattinger Dr. Xabier Larrea Dr. Hicham Majd Lab assistants Sandra Jaccoud Corinne Scaletta

Blecha, L.D., Rakotomanana, L., Razafimaheri, F., Terrier, A., Pioletti, D.P. (2010).Mechanical interaction between cells and fluid for bone tissue engineering scaffold: modulation of the interfacial shear stress. J Biomechanics 43: 933-937.

Engineers Vittoria Brighenti Damien Joss Silvio Ramondetti Patricia Scheuber

Roshan Ghias, A., Terrier, A., Bourban, P.E., Pioletti, D.P (2010). In vivo cyclic loading as a potent stimulatory signal for bone formation inside tissue engineering scaffolds. e Cells Materials 19:41-49.

PhD students Philippe Abdel-Sayed Salim Darwich Michael Gortchacow Jérôme Hollenstein (UCSD) Ulrike Kettenberger Nassajian Moghadam Mohamadreza Alireza Roshan Ghias Marion Röthlisberger Arne Vogel

Pioletti, D.P. (2010) Biomechanics in bone tissue engineering. Comp Meth Biomech Biomed Eng 13:837-846. Terrier, A., Aeberhard, M., Michellod, Y., Mullhaupt, P., Gillet, D., Farron, A., Pioletti, D.P. (2010) A musculoskeletal shoulder model based on pseudoinverse and null-space optimization. Med Eng Phys 32: 1050-1056. van der Pol, U., Mathieu, L., Zeiter, S., Bourban, P.E., Zambelli, P.Y., Pearce, S.G., Bouré, L., Pioletti, D.P. (2010) Augmentation of bone defect healing using a new biocomposite scaffold:an in vivo study in sheep. Acta Biomaterialia 6:3755-3762.

Master students Yannick Bastin Fabien Duc Michael Ducret Aurelien Gallice Florian Herzog Fabienne Meier Andreas Schmocker

Stadelmann, V.A., Bretton, E., Terrier, A., Procter, P., Piolett,i D.P. (2010) Calcium phosphate cement augmenta-

Administrative Assistant Virginie Kokocinski

EPFL School of Life Sciences - 2010 Annual Report

Psaltis Lab

- coaffiliated STI

http://lo.epfl.ch/ Demetri Psaltis was educated at Carnegie-Mellon University where he received the Bachelor of Science degree in Electrical Engineering and Economics in 1974, the Master’s in 1975, and the PhD in Electrical Engineering in 1977. In 1980, he joined the faculty at the California Institute of Technology, Pasadena, California and he served as Executive Officer for the Computation and Neural Systems department from 1992-1996. From 1996 until 1999 he was the Director of the National Science Foundation research center on Neuromorphic Systems Engineering at Caltech as well as the director of the Center for Optofluidic Integration. In 2007, he moved to the EPFL where he is professor and director of the optics laboratory and also the Dean of School of Engineering. Full Professor Dean of the School of Engineering

He has authored or co-authored over 400 publications in these areas. Dr. Psaltis is a fellow of the IEEE, the Optical Society of America and the Society for Photo-optical Systems Engineering (SPIE). He received the International Commission of Optics Prize, the Humboldt Award, and the Gabor prize. He is the co-founder of Ondax.

Research Interests

The activities of the Optics Laboratory primarily focus onto two research areas. First, we work within the field of Optofluidics, where the objective is to develop novel photonic devices and analytical methods by fusing integrated optics and microfluidics. Typical examples involve on-chip molecular spectroscopy, where individual components such as light sources, filters and switches have been developed. In parallel, we have also explored the importance of surfaces in optofluidics, primarily focusing on the manipulation of DNA, the use of plasmonic nanoparticles of advanced mass transport and the employment of electrical fields for flow and bio-entity control. Such methodologies are currently employed to address challenges within the field of biophysics. The second research focus is in nonlinear optics and consists of two different research axes: new microscopy techniques for imaging in diffusive media such as biological tissue, and imaging in nonlinear media. In regards to the former, we are exploring nanoparticles that consist of non-centrosymmetric crystal structures as sources of second-harmonic generation (SHG); these nanoparticles have shown great promise as imaging probes due to their coherent and stable signals. In regards to the latter, we investigate how to optimize image transmission through non-linear media. This technique is promising for both enhanced resolution imaging, but also novel methods to analyse the non-linear properties of liquid media.

Selected

meter with polymer interferometers defined by soft lithography’, Optics Express 18, 16561 (2010). Y. Pu, R. Grange, C.-L. Hsieh, D. Psaltis, ‘Nonlinear optical properties of core-shell nanocavities for enhanced second-harmonic generation’ Physical Review Letters 104, 207402 (2010). W. Z. Song, A. E. Vasdekis, Z. Li, D. Psaltis, ‘Low order distributed feedback optofluidic dye laser with reduced threshold’ Applied Physics Letters 94, 051117 (2009). D. Psaltis, S. R. Quake, C. Yang, ‘Developing optofluidic technology through the fusion of microfluidics and optics’, Nature 442, 381 (2006).

Team Members

Post-doctoral Fellows Ye Pu Andreas Vasdekis Jae-Woo Choi Chia-Lung Hsieh

IBI - Co-affiliated Research Groups

Demetri Psaltis

PhD students Wuzhou Song Alexandre Goy Julien Cuennet Ioannis Papadopoulos Xin Yang Grégoire Laporte Jianhang Yang Administrative Assistant Carole Berthet

publications

J. G. Cuennet*, A. E. Vasdekis*, L. De Sio, D. Psaltis, ‘Optofluidic modulators based on nematogen microflows’, Nature Photonics 5, 234 (2011). A. Goy, D. Psaltis, ‘Digital reverse propagation in focussing Kerr media’ Physical Review A 83, 031802 (2011). W. Z. Song, D. Psaltis, ‘Imaging based optofluidic air flow

EPFL School of Life Sciences - 2010 Annual Report

Radenovic Lab -

coaffiliated STI

http://lben.epfl.ch/

IBI

Aleksandra Radenovic earned a degree in physics from the University of Zagreb before joining Professor Giovanni Dietler’s. There she earned her Doctor of Sciences degree in 2003. She then undertook postdoctoral study at the University of California, Berkeley. From July 2008 she is an assistant tenure tracked professor at the institute of Bioengineering.

Aleksandra Radenovic Tenure Track Assistant Professor School of Engineering

Research Interests

The research of the Laboratory of Nanoscale Biology focuses on developing tools and probes for single-molecule biophysics. The group uses optical tweezers, AFM, single-molecule fluorescence, PhotoActivated Light microscopy PALM and nanofabricated structures to study biomolecular systems and advance new nanotechnology. Current experimental work in our lab focuses on two interconnecting areas: Nanofabricated probes and platforms for singlemolecule biophysics experiments Including nanofabricated SHG nanocylinders, solidstate nanopores, local nanolectrodes for molecular sensing and sequencing DNA nanotechnology Our main focus is to implement DNA origami structures into nanoelectronics. We use grapheme nanoribbon templates onto which different DNA origami structures can self-assemble and would enable us to register individual molecular nanostructures, to electronically address them, and to integrate them into functional devices.. Local probe studies of single biomolecules For example RNA polymerase, DNA binding proteins, membrane proteins such G protein–coupled receptors (GPCRs ).

Selected

Miklossy J., Qing H., Radenovic A., Kis A., Villeno B. , Laszlo F., Miller L., Martins R., Waeberf G., Mooser V., Bosman F., Khalilii K., Darbinian-Sarkissian N., McGeer P.L., Beta amyloid and hyperphosphorylated tau deposits in the pancreas in type 2 diabetes Neurobiology of Aging, Volume 31, Issue 9, Pages 1503-1515 (2010) Annibale P., Scarselli M., Kodiyan,A and Radenovic A., Photoactivatable Fluorescent Protein mEos2 Displays Repeated Photoactivation after a Long-Lived Dark State in the Red Photoconverted Form The Journal of Physical Chemistry Letters, 2010, 1, pp 1506–1510

Team Members Post doctoral Scarselli Marco Traversi Floriano PhD Students Annibale Paolo Brando Serena t Dutto Fabrizia Raillon Camille Master students Matia Greco Administrative Assistant Chong Helen

publications

Radisavljevic B., Radenovic A., Brivio J., Giacometti V., A. Kis, 1*Single-layer MoS2 transistors, Nature Nanotechnology, vol. 6, p. 147, 2011. (also featured on the cover) Sudhir Husale, Sangeeta Sahoo, Aleksandra Radenovic, Floriano Traversi, Paolo Annibale, and Andras Kis ssDNA Binding Reveals the Atomic Structure of Graphene , Langmuir, Volume, 26 (23), pp 18078–18082 (2010)

EPFL School of Life Sciences - 2010 Annual Report

Stergiopulos Lab -

coaffiliated STI

http://lhtc.epfl.ch Nikos Stergiopulos studied Mechanical Engineering at the National Technical University of Athens, Greece and obtained his Ph.D. in Biomedical Engineering from Iowa State University in 1990. His research interests are Hemodynamics, Cardiovascular Mechanics and Medical Implant Technology. He has authored more than 100 publications and holds more than 15 patents in medical technology. He co-founded EndoArt, world leader in telemetric implants for the treatment of congenital heart disease and morbid obesity and Antlia SA, developer of implantable drug delivery pumps.

Nikos Stergiopulos Full Professor School of Engineering

The Laboratory of Hemodynamics and Cardiovascular Technology (LHTC) focuses is on the relation between blood flow and the development, progression and regression of cardiovascular disease. Development of vascular implants and non-invasive or mini-invasive technologies for the diagnosis and treatment of disease is also a major objective.

Selected

publications

Thacher TN, Silacci P, Stergiopulos N, and da Silva RF. (2010). Autonomous Effects of Shear Stress and Cyclic Circumferential Stretch regarding Endothelial Dysfunction and Oxidative Stress: An ex vivo Arterial Model. Journal of Vascular Research 47: 336-345. Thacher TN, Gambillara V, Riche F, Silacci P, Stergiopulos N, and da Silva RF. (2010). Regulation of arginase pathway in response to wall shear stress. Atherosclerosis 210: 63-70. Tsamis A, Stergiopulos N, and Rachev A. (2009). A structure-based model of arterial remodeling in response to sustained hypertension. J Biomech Eng 131: 101004. Reymond P, Merenda F, Perren F, Rufenacht D, and Stergiopulos N. (2009). Validation of a one-dimensional model of the systemic arterial tree. Am J Physiol Heart Circ Physiol 297: H208-222, 2009.

Team Members Engineers Michel Bachmann Stéphane Bigler

Scientific collaborators & Post docs Luciano Capettini Rafaela Fernandes da Silva Dimitrios Kontaxakis Bryn Martin Sylvain Roy PhD students Aristotelis Agianniotis Thiresia Gialourou Philippe Reymond Rana Rezakhaniha Orestis Vardoulis Adan Villamarin Masters students Eline Coppens Mustapha Alkharfane Reda Hesbala Gaëlle Diserens David Petio

IBI - Co-affiliated Research Groups

Research Interests

Administrative Assistant Tamina Sissoko

Reymond P, Merenda F, Perren F, Rufenacht D, and Stergiopulos N. (2009). Validation of a one-dimensional model of the systemic arterial tree. Am J Physiol Heart Circ Physiol 297: H208-222, 2009. Fonck E, Feigl GG, Fasel J, Sage D, Unser M, Rufenacht DA, and Stergiopulos N. (2009). Effect of aging on elastin functionality in human cerebral arteries. Stroke 40: 2552-2556.

EPFL School of Life Sciences - 2010 Annual Report

Van de Ville Lab

- coaffiliated STI

http://miplab.epfl.ch/

IBI

M.S. and Ph.D. in Computer Sciences from Ghent University, Belgium (1998, 2002), postdoc at EPFL (2002-2005), research associate and coordinator of the CIBM Signal Processing Unit at University of Geneva (2005-2009), awarded SNSF professorship (2009) and currently tenure-track assistant professor affiliated with EPFL and University of Geneva. Vice-Chair of the Biomedical Image & Signal Processing Technical Committee of the IEEE Signal Processing Society. Associate Editor of IEEE Transactions on Image Processing (2006-2009) and Guest Editor of the Special Issue on Brain Decoding in Elsevier Pattern Recognition.

Dimitri Van De Ville SNSF Professor School of Engineering

Research Interests

Our goal is to advance our understanding of the human body, in particular of brain function in health and disorder using non-invasive imaging techniques. To that aim, we pursue the development and integration of innovative methodological tools from signal and image processing at various stages of the acquisition, processing, and analysis pipeline. The first highlight of our research is on temporal dynamics of spontaneous brain activity; e.g., we showed fractal organization of the rapid switching between scalp topographies in spontaneous EEG and how it interlinks with fMRI that is governed by slow hemodynamics. The second highlight is the analysis of functional brain networks using multi-scale graph models and techniques from pattern recognition to interpret and predict cognitive and clinical conditions based on signatures of functional connectivity.

Selected

publications

Van De Ville, D., Britz, J., and Michel, C. M. (2010). EEG Microstate Sequences in Healthy Humans at Rest Reveal Scale-Free Dynamics. Proc. Natl. Acad. Sci. U S A. 107(42), 18179-18184. Binzoni, T., Seelamantula, C. S., and Van De Ville, D. (2010). A Fast Time-Domain Algorithm for the Assessment of Tissue Blood Flow in Laser-Doppler Flowmetry. Physics in Medicine and Biology, 55, N383-N394.

Raabe, A., Van De Ville, D., Leutenegger, M., Szelényi, A., Hattingen, E., Gerlach, R., Seifert, V., Hauger, C., Lopez, A., Leitgeb, R., Unser, M., Martin-Williams, E. and Lasser, T. (2009). Laser Doppler Imaging for Intraoperative Human Brain Mapping. NeuroImage, 44(4), 12841289.

Team Members Post-doctoral Ivana Jovanovic Cauchy Pradhan Jonas Richiardi Frank Scharnowski Yves Wiaux PhD students Djano Kandaswamy Isik Karahanoglu Jeffrey Kasten Nora Leonardi Master’s students Maryna Babayeva Jose Antonio Lopez Moreno Vagia Tsiminaki Administrative Assistant Ruth Fiaux

Unser, M. and Van De Ville, D. (2010). Wavelet Steerability and the Higher-Order Riesz Transform. IEEE Transactions on Image Processing, 2010, 19(3), 636-652. Ethofer, T., Van De Ville, D., Scherer, K. and Vuilleumier, P. (2009). Decoding of Emotional Information in VoiceSensitive Cortices. Current Biology, 19(12), 1028-1033. Kandaswamy, D., Blu, T. and Van De Ville, D. (2009) Analytic Sensing: Noniterative Retrieval of Point Sources from Boundary Measurements. SIAM Journal on Scientific Computing, 31(4), 3179-3194.

EPFL School of Life Sciences - 2010 Annual Report

Van den Bergh Lab -

coaffiliated STI

http://lpas/PDT Hubert van den Bergh obtained a BA in chemistry at Williams College Massachusetts USA, a PhD in physical chemistry at Cambridge University UK, and did postdoctoral work in physics at the Max Planck Institut für Strömungsforschung in Göttingen Germany. He is professor at EPFL and a member of the Council of the Swiss National Science Foundation. He was awarded the prize of the Swiss Chemical Society, the Ruzicka Prize and the prize of the Swiss Biomedical Technology Society.

Hubert van den Bergh Full Professor School of Engineering

Hubert van den Bergh has contributed in the fields of basic chemical kinetics (including the development of the T-jump method in the gas-phase and molecular beam investigations of the cage effect), laser- and beam-induced chemical vapor deposition, and air pollution studies (modeling and measurements). The atmospheric measurements by LIDAR include a Raman system for measuring H2O vapor and temperature that was delivered to the Swiss Meteorological Institute for routine daily round the clock measurements. Other contributions include a novel method for the separation of isotopes by laser-induced inhibition of condensation, which has led to the large scale separation of Uranium isotopes now in use at Wilmington NC by GE, Hitachi and Cameco. Contributions to photomedicine include part of the development of Visudyne® technology for the treatment of wet age-related macular degeneration (FDA approval in 2000) with Novartis and QLT, the development of Hexvix® for the detection and removal of early stage bladder cancer (FDA approval in 2010) with Photocure and GE Healthcare, and the development of a fluorescence endoscope with Wolf GmbH in Germany.

Selected

publications

Gabriel D., Zuluaga M.F., van den Bergh H., Gurny R., and Lange N. (Accepted). It is all about proteases: from drug delivery to in vivo imaging and photomedicine, Current Medical Chemistry. Nowak-Sliwinska P., Ballini J.-P., Wagnières G., van den Bergh H.. (2010). Processing of fluorescence angiograms for the quantification of vascular effects induced by anti-angiogenic agents in the CAM model, Microvascular Research, 79, 21-28. Nowak-Sliwinska P., van Beijnum J.R., van Berkel M., van den Bergh H. and Griffioen A.W. (2010). Vascular regrowth following photodynamic therapy in the chicken embryo chorioallantoic membrane, Angiogenesis, 13, 281-292. Cheng C., Debefve E., Haouala A., Andrejevic Blant S., Krueger T., Ballini J.-P., Peters S., Decosterd L.-A., van den Bergh H., Wagnières G., Perentes Y., and Ris H.-B. (2010). Photodynamic therapy selectively enhances liposomal Doxorubicin uptake in sarcoma tumors to rodent lungs, Lasers in Surgery and Medicine, 42, 391-399.

Debefve E., Cheng C., Schaefer S.C., Yan H., Ballini J.P., van den Bergh H., Lehr H.-A., Ris H.-B., and Krueger T. (2010). Photodynamic therapy induces selective extravasation of macromolecules : Insights using intravital microcospy, Journal of Photochem. and Photobiol. B ; Biology 98, 69-76. Lovisa B., Jichlinski P., Weber B.C., Aymon D., van den Bergh H., and Wagnières G. (2010). High-magnification vascular imaging to reject false-positive sites in situ during Hexvix ® fluorescence cystoscopy, Journal of Biomedical Optics, 15(5), 051606, 1-8. Gabrecht T., Lovisa B., van den Bergh H., and Wagnières G. (2009). Autofluorescence bronchoscopy: quantification of inter-patient variations of fluorescence intensity intensity, Lasers in Medical Sciences, 24(1), 45-51. Gabriel D., Busso N., So A., van den Bergh H., Gurny R. and Lange N. (2009). Thrombin-sensitive photodynamic agents : A novel strategy for selective synovectomy in rheumatoid arthritis, Journal of Controlled Release, vol.138, (3), 225-234.

Team Members

Postdoctoral Thomas Braschler Elodie Debefve Sandrine Gay Blaise Lovisa Karine Mondon Senthil Kumar Rajendran Patrycja Nowak-Sliwinska Magdalena Swiderska Georges Wagnières Yaboo Wang

IBI - Co-affiliated Research Groups

Research Interests

PhD Students Gilles Kratzer Cédric Paulou Master’s Students Deborah Forte Stephanie Kappel Carla Martoccia Vincent Mazoyer Andrea Weiss Administration Véronique Bauler Roxane Mischler

EPFL School of Life Sciences - 2010 Annual Report

IBI - Institute of Bioengineering

EPFL School of Life Sciences - 2010 Annual Report

Auwerx - Schoonjans Lab http://auwerx-lab.epfl.ch/

IBI

Johan Auwerx and Kristina Schoonjans use a systems physiology approach to understand metabolic homeostasis and the pathogenesis of common metabolic diseases.

Johan Auxerx, MD, PhD Full Professor Nestle Chair in Energy Metabolism

Kristina Schoonjans Professeur Titulaire

Introduction

Keywords

Diabetes, genetics, metabolism, metabolic disease, phenogenomics, transcription

Results Obtained in 2010

EPFL School of Life Sciences - 2010 Annual Report

Selected

Publications

Team Members

Lab Technicians Sabrina Bichet Thibaud Clerc Marie-Laure Dénéreaz, until September 2010 Amandine Moriot-Signorino-Gelo Norman Moullan

Administrative Assistant Valérie Stengel

IBI - Institute of Bioengineering

Mice treated with resveratrol are protected from obesity.

EPFL School of Life Sciences - 2010 Annual Report

Barrandon Lab http://ldcs.epfl.ch/

IBI

Yann Barrandon

Full Professor, EPFL / CHUV Head of Experimental Surgery CHUV

Introduction

Keywords

Stem cells, metaplasia, micro-environment, skin, thymus, cell and gene therapy

Results Obtained in 2010

EPFL School of Life Sciences - 2010 Annual Report

Selected

Publications

Team Members Senior scientists Brouard Michel Rochat Ariane

IBI - Institute of Bioengineering

Administrative Staff Guex Nathalie

Blistering of the skin in a patient suffering from Recessive Dystrophy Epidermolysis Bullosa. Deficient Collagen VII is immunostained in red.

EPFL School of Life Sciences - 2010 Annual Report

Dal Peraro Lab http://lbm.epfl.ch

IBI

Matteo Dal Peraro Tenure-track Assistant Professor

Introduction

Keywords

Computational biophysics, biochemistry, and structural biology; bacteria and viruses; multi scale molecular simulations; macromolecular assembly; protein and drug design; high-performance computing

Results Obtained in 2010

EPFL School of Life Sciences - 2010 Annual Report

Selected

Publications

Team Members Post doctoral Davide Aleman Marco Stenta

PhD Students Christophe Bovigny Matteo Degiacomi Hassan Pezeshki Thomas Lemmin Enrico Spiga

Adnimistrative Assistant Marie-France Radigois

IBI - Institute of Bioengineering

EPFL School of Life Sciences - 2010 Annual Report

Deplancke Lab

http://deplanckelab.epfl.ch/

IBI

Bart Deplancke Tenure-track Assistant Professor

Introduction

Keywords

Systems Biology, Gene Regulatory Network, Transcription, Quantitative Genetics, Mouse, Drosophila, Yeast, Genetic Engineering

Results Obtained in 2010

EPFL School of Life Sciences - 2010 Annual Report

Publications

Team Members

IBI - Institute of Bioengineering

Selected

EPFL School of Life Sciences - 2010 Annual Report

Hubbell Lab http://lmrp.epfl.ch

IBI

Jeffrey A. Hubbell

Full Professor Director of IBI Merck-Serono Chair in Drug Delivery

Introduction

Keywords

Biomaterials, tissue engineering, protein engineering, extracellular matrix, immunobioengineering, vaccines

Results Obtained in 2010

Vaccines and immunotherapeutics: In collaboration with the Laboratory for Lymphatic

EPFL School of Life Sciences - 2010 Annual Report

Selected

Publications

IBI - Institute of Bioengineering

Internships Diplas Bill Ferreira Daniela Hopkins Amy Wanakule Prinda

EPFL School of Life Sciences - 2010 Annual Report

Lutolf Lab http://lscb.epfl.ch

IBI

Matthias P. Lutolf Tenure-track Assistant Professor

Introduction

Keywords

Stem cells, self-renewal, single cell analysis, niche, hydrogel engineering, microfluidics

Results Obtained in 2010

EPFL School of Life Sciences - 2010 Annual Report

Selected

Publications

Kobel, M., Limacher, M., Gobaa, S. Lutolf, M.P. (2009). Soft embossing of hydrogels, Langmuir, 25 (15): 8774–8779

IBI - Institute of Bioengineering

Jo Y.S., Gantz, F., Hubbell, J.A., Lutolf, M.P. (2009), Tailoring hydrogel degradation and drug release via neighboring amino acid-controlled ester hydrolysis, Soft Matter, 5: 440-446

EPFL School of Life Sciences - 2010 Annual Report

Naef Lab

http://naef-lab.epfl.ch/

IBI

Felix Naef

Tenure-track Assistant Professor

Introduction

Keywords

Circadian transcription, chronobiology, circadian clocks precision, fluctuations and bursting in gene expression spatio-temporal model of patterning in the early Drosophila embryo

Results Obtained in 2010

EPFL School of Life Sciences - 2010 Annual Report

Selected

Publications

Team Members Post doctoral Teresa Ferraro Nacho Molina Bhaswar Ghosh

IBI - Institute of Bioengineering

EPFL School of Life Sciences - 2010 Annual Report

Swartz Lab

http://swartz-lab.epfl.ch

IBI

Melody A. Swartz Full Professor

Introduction

Keywords

Lymphatic, lymph node, immunity, tolerance, tumor, metastasis, interstitial flow, mechanobiology

Results Obtained in 2010

EPFL School of Life Sciences - 2010 Annual Report

Selected

Publications

Team Members Post doctoral Sachiko Hirosue Witold Kilarski Amanda Lund Evan Scott Adrian Shieh Jacqui Shields Jeremy Teo Susan N. Thomas

PhD Students Marie Ballester Alexandre de Titta Esra Guç Laura Jeanbart Ulrike Haessler Iraklis Kourtis Marco Pisano Sandeep Raghunathan Valentina Triacca

Lund, A.W. and Swartz, M.A. (2010). Role of lymphatic vessels in tumor immunity: Passive conduits or active participants? J Mammary Gland Biol Neoplasia 15(3):341-52.

Visiting scholars Vidya Raghavan (Fulbright Fellow) Vanessa Kennedy (Whitaker Fellow)

Master’s Students Marcela Rincon Ristrepo Efthymia Vokali

Administrative Assistant Ingrid Margot

IBI - Institute of Bioengineering

EPFL School of Life Sciences - 2010 Annual Report

Wurm Lab

http://lbtc.epfl.ch

IBI

Florian M. Wurm Full Professor

Introduction

Keywords

Recombinant protein expression - Mammalian cell culture – Bioreactor – Bioprocess control – Gene transfer - DNA integration - Microinjection - Stable cell line development – Orbital shaking

Results Obtained in 2010

EPFL School of Life Sciences - 2010 Annual Report

Publications

Team Members

IBI - Institute of Bioengineering

Selected

Metaphase and nuclei of lentivirus infected CHO cells. Metaphasic chromosomes and nuclei are DAPI stained. Integration sites are visualized by using Fluorescence in situ hybridization (FISH).

EPFL School of Life Sciences - 2010 Annual Report

Aminian Lab -

coaffiliated STI

http://lmam.epfl.ch/

IBI

Kamiar Aminian Adjunct Professor School of Engineering

Research Interests

Selected

Publications

EPFL School of Life Sciences - 2010 Annual Report

Fantner Lab -

coaffiliated STI

Research Interests

Selected

Publications

Team Members Post doctoral Jonathan Adams Blake Erickson

Master’s Students Benea-Chelmus Ileana-Cristina ADministrative Assistant Tamina Sissoko

IBI - Co-affiliated Research Groups

EPFL School of Life Sciences - 2010 Annual Report

Guiducci Lab

- coaffiliated STI

http://clse.epfl.ch

IBI

Carlotta Guiducci

Tenure-track Assistant Professor Swiss Up Engineering Chair School of Engineering

Research Interests

Selected

Publications

EPFL School of Life Sciences - 2010 Annual Report

Hatzimanikatis Lab -

coaffiliated SB

http://lcsb.epfl.ch

Associate Professor School of Basic Sciences

Research Interests

Selected

Publications

Team members Research Associates Ljubisa Miskovic

IBI - Co-affiliated Research Groups

Vassily Hatzimanikatis

“Network thermodynamics in the post-genomic era”, Keng Cher Soh and Vassily Hatzimanikatis, Curr. Opin. Microbiol., 13 (3), 350-357 (2010).

EPFL School of Life Sciences - 2010 Annual Report

Ijspeert Lab -

coaffiliated STI

http://biorob.epfl.ch/

Auke Ijspeert Associate Professor School of Engineering

Research Interests

Selected

Publications

Team Members

IBI

EPFL School of Life Sciences - 2010 Annual Report

Johnsson Lab

- coaffiliated SB

http://isic.epfl.ch/lip

Kai Johnnson Full Professor School of Basic Sciences

Selected

Publications

Team Members

IBI - Co-affiliated Research Groups

Research Interests

Administrative Assistant Marie-Claude Gasparini

EPFL School of Life Sciences - 2010 Annual Report

Jolles-Haeberli Lab http://cbt.epfl.ch

Brigitte Jolles-Haeberli Adjunct Professor School of Engineering Director of CBT

Research Interests

Selected

Center Groups

LBO Lab LMAM Lab for Orthopaedic & sport medicine activities

Administrative Assistant Sabrina Martone

Publications

IBI

- coaffiliated STI

EPFL School of Life Sciences - 2010 Annual Report

Maerkl Lab

- coaffiliated STI

Sebastian Maerkl Tenure Track Assistant Professor School of Engineering

Selected

Publications

Team Members

IBI - Co-affiliated Research Groups

Research Interests

Master’s Students Valoise Mendoh Mangoua Administrative Assistant Helen Chong

EPFL School of Life Sciences - 2010 Annual Report

Mermod Lab -

coaffiliated IBI/UNIL

http://www.unil.ch/biotech

Nicolas Mermod

IBI

Full Professor IBI-UNIL

Research Interests

Our research can be summarized in four main areas: •

Genetic regulation by cell growth factors and tissue regeneration http:// www.unil.ch/Jahia/site/biotech/pid/37429

•

Expression of genes of biotechnological interest in mammalian cells http:// www.unil.ch/Jahia/site/biotech/pid/37430

•

Characterization and modeling of genomic and epigenetic regulators http:// www.unil.ch/Jahia/site/biotech/pid/38548

•

Development of more efficient and safer gene therapy vectors http:// www.unil.ch/Jahia/site/biotech/pid/37432

Selected

Publications

Team Members

EPFL School of Life Sciences - 2010 Annual Report

Millán Lab

- coaffiliated STI

José del Rocio Millán Associate Professor Defitech Professor School of Engineering

Selected

Publications

IBI - Co-affiliated Research Groups

Research Interests

Research Assistants Benjamin Hamner Guillaume Monnard Administrative Assistant Eva Gasser

EPFL School of Life Sciences - 2010 Annual Report

Pioletti Lab

- coaffiliated STI

http://lbo.epfl.ch

IBI

Dominique P. Pioletti Tenure Track Assistant Professor School of Engineering

Research Interests

Selected

Publications

Team Members

Group leaders Prof. Lee A. Laurent-Applegate Dr. Alexandre Terrier Post-doctoral fellows Dr. Nathalie Krattinger Dr. Xabier Larrea Dr. Hicham Majd Lab assistants Sandra Jaccoud Corinne Scaletta

Engineers Vittoria Brighenti Damien Joss Silvio Ramondetti Patricia Scheuber

PhD students Philippe Abdel-Sayed Salim Darwich Michael Gortchacow Jérôme Hollenstein (UCSD) Ulrike Kettenberger Nassajian Moghadam Mohamadreza Alireza Roshan Ghias Marion Röthlisberger Arne Vogel

Master students Yannick Bastin Fabien Duc Michael Ducret Aurelien Gallice Florian Herzog Fabienne Meier Andreas Schmocker

Stadelmann, V.A., Bretton, E., Terrier, A., Procter, P., Piolett,i D.P. (2010) Calcium phosphate cement augmenta-

Administrative Assistant Virginie Kokocinski

EPFL School of Life Sciences - 2010 Annual Report

Psaltis Lab

- coaffiliated STI

Research Interests

Selected

Team Members

Post-doctoral Fellows Ye Pu Andreas Vasdekis Jae-Woo Choi Chia-Lung Hsieh

IBI - Co-affiliated Research Groups

Demetri Psaltis

PhD students Wuzhou Song Alexandre Goy Julien Cuennet Ioannis Papadopoulos Xin Yang Grégoire Laporte Jianhang Yang Administrative Assistant Carole Berthet

publications

EPFL School of Life Sciences - 2010 Annual Report

Radenovic Lab -

coaffiliated STI

http://lben.epfl.ch/

IBI

Aleksandra Radenovic Tenure Track Assistant Professor School of Engineering

Research Interests

Selected

publications

EPFL School of Life Sciences - 2010 Annual Report

Stergiopulos Lab -

coaffiliated STI

Nikos Stergiopulos Full Professor School of Engineering

Selected

publications

Team Members Engineers Michel Bachmann Stéphane Bigler

IBI - Co-affiliated Research Groups

Research Interests

Administrative Assistant Tamina Sissoko

EPFL School of Life Sciences - 2010 Annual Report

Van de Ville Lab

- coaffiliated STI

http://miplab.epfl.ch/

IBI

Dimitri Van De Ville SNSF Professor School of Engineering

Research Interests

Selected

publications

EPFL School of Life Sciences - 2010 Annual Report

Van den Bergh Lab -

coaffiliated STI

Hubert van den Bergh Full Professor School of Engineering

Selected

publications

Team Members

Postdoctoral Thomas Braschler Elodie Debefve Sandrine Gay Blaise Lovisa Karine Mondon Senthil Kumar Rajendran Patrycja Nowak-Sliwinska Magdalena Swiderska Georges Wagnières Yaboo Wang

IBI - Co-affiliated Research Groups

Research Interests

PhD Students Gilles Kratzer Cédric Paulou Master’s Students Deborah Forte Stephanie Kappel Carla Martoccia Vincent Mazoyer Andrea Weiss Administration Véronique Bauler Roxane Mischler

EPFL School of Life Sciences - 2010 Annual Report