The Wellcome Trust/ Cancer Research UK Gurdon Institute
2016 Prospectus Annual report 2015
Studying development to understand disease
25 YEARS
The Wellcome Trust/ Cancer Research UK Gurdon Institute
2016 Prospectus Annual report 2015
Contents Director’s welcome About the Institute What does it mean to be an institute? Who works at the Institute? What are the opportunities for postgraduates? How can postdocs apply for a position? Where does the Institute’s funding come from? Who oversees our scientific activity? Focus on research Julie Ahringer Andrea Brand Jenny Gallop John Gurdon Martin Hemberg Meritxell Huch Steve Jackson Tony Kouzarides Rick Livesey Eric Miska Eugenia Piddini Emma Rawlins
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Contents
3 4 5 6 6 6 7 8 10 12 14 16 18 20 22 24 26 28 30
Ben Simons Daniel St Johnston Azim Surani Philip Zegerman Alex Sossick
The Gurdon Institute in 2015 People Senior group leaders Group leaders Visiting students/researchers Core staff Group leader affiliations and editorial boards Publications in 2015 Activities and impacts in 2015 Awards and prizes Global reach in 2015 Engaging the public Events and media highlights Seminars and celebrations
32 34 36 38 40
42 48 50 52 54 55 60 62 64 66 68
Welcome In 2016 we are celebrating 25 years of the Gurdon Institute
Welcome to the Gurdon Institute 2016 Prospectus/ Annual report 2015. Inside you will learn about the latest advances in our research on developmental biology and cancer biology (pp. 8–39), and find further information on what makes the Institute a rewarding place in which to pursue a research career. Congratulations are due to Steve Jackson for winning the Gagna A. and Ch. Van Heck Prize 2015 for his work on the DNA damage response, and Ben Simons for receiving the Royal Society’s Gabor Medal in recognition of his interdisciplinary research that uses approaches from physics to explore stem cell biology (see more on pp. 60–61). Other notable events in 2015 included the opening of the Alzheimer’s Research UK Stem Cell Research Centre by John Gurdon, with Kirsten Rausing of the Alborada Trust, who donated the funding (pp. 66–67). A record of our research publications in 2015 is shown on pages 55–59. Many of these and our other impacts have attracted attention from both mainstream and social media. With some sadness, we note the departure in October 2015 of one of our longest-serving group leaders, Jonathon Pines, who was recruited to head the Division of Cancer Biology at the Institute of Cancer Research in London. Another very early Institute member to whom we bid farewell is Nick Brown, who moved his lab at the end of January 2016 to the University Department of Physiology, Development and Neuroscience. Meanwhile, our new associate group leader Martin Hemberg will bring another dimension of expertise to our quantitative analysis of biological data. Other leavers in 2015 have spread out around the world (pp. 62–63) in high-profile scientific roles. Looking across our 25-year history we have gathered data for over 660 alumni, 186 of whom are now group leaders - showing how the Institute provides a springboard for successful careers in science. I hope you enjoy reading about the Gurdon Institute!
Director February 2016 The Gurdon Institute
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About the Institute The Gurdon Institute is funded by the Wellcome Trust and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.
The Gurdon Institute is a world-leading centre for research at the interface between developmental biology and cancer biology. We focus on several related topics: cell division, proliferation and genome maintenance; function and regulation of the genome and epigenome; mechanisms of cell fate determination, multipotency and plasticity; and the cell biological processes underlying organ development and function. We investigate these areas in both normal development and cancer using several model systems, from yeast to human organoids. Across our 25-year history, our research has led to major insights into the molecular and cellular defects that give rise to cancer and other diseases of ageing, and several of our findings have been successfully translated into drug discovery through spin-out companies.
What does it mean to be an institute? “world-leading centre for research”
“inclusive, family atmosphere”
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About the Institute
As a research institute within the University of Cambridge’s School of Biological Sciences we enjoy collaborations and joint activities with Departments close by, where our group leaders are members and contribute to teaching. But beyond being part of the local intellectual environment, our researchers gain additional benefits from our institute status: •
Exposure and access to a diverse range of research questions, model organisms and techniques, all under one roof (see pp. 8–39)
•
Purpose-built laboratories with shared core facilities and access to state-of-the-art equipment
•
Expert technical support for imaging and image analysis (pp. 40–41), next-generation sequencing and bioinformatics
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Central services providing administration, computing and IT support, and media preparation and glass washing – all with a smile
•
Frequent internal and external seminars and masterclasses, and an Institute association for postdocs (pp. 68–69)
•
Public engagement programme for exchange and reciprocal learning between our scientists and the wider public (pp. 64–65)
•
On-site catering and a variety of social events, from weekly ‘happy hours’ to the Christmas party, to promote our inclusive, family atmosphere (p. 69). BR AN D
MI SK A
N SO CK JA
HEM BERG
SIMON S
DON GUR
NS RAWLI HU CH
NI DI PID
At any one time there are around 240 scientists at the Institute and up to 60 core support staff (pp. 42–54). There are typically over 30 nationalities represented and dozens of languages spoken. The Institute has an Athena SWAN Bronze Award for promoting equality across the workforce.
NI RA SU
OP LL GA
We currently have 14 group leaders and two associate group leaders (pp. 8–39), and intend to recruit two more full group leaders in 2016. We pride ourselves on the number of internal collaborations (right), both formal and informal, generated across the Institute.
AHRING ER
ST JO HN ST O N
Who works at the Institute?
ERMAN ZEG
LIVE SEY
IDES KOUZAR
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What are the opportunities for postgraduates?
“we have a thriving population of graduates”
We welcome enquiries from prospective graduate students. We have a thriving population of graduates who contribute greatly to both the stimulating research environment and the life of the Institute as a whole. Graduates also become members of the biological or medical sciences department to which their group is affiliated. Graduate studentships are supported from various public and private sources. The Wellcome Trust finances a number of schemes in the University, including one in developmental mechanisms and one in stem cells. The Cambridge Cancer Centre also provides studentships. Applicants should write to the leader of the group they wish to join (get in touch by email at contact@gurdon.cam.ac.uk).
How can postdocs apply for a position? We advertise positions for postdocs through the University’s website at www.jobs.cam.ac.uk and also on www.jobs.ac.uk, and group leaders are also happy to be contacted directly by motivated researchers wishing to develop their careers in the relevant field.
Where does the Institute’s funding come from? The Wellcome Trust and Cancer Research UK are our principal sponsors, through our core grant and through programme grants to group leaders. In addition we benefit from several other funding sources including charitable donations, as shown in the chart (right).
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About the Institute
Grant Funding 2014 to 2015
Wellcome Trust
Royal Society
Cancer Research UK
Other Charity
EC
Other
UK Research Councils
Who oversees our scientific activity? The Institute is overseen by a Management Committee, whose Chair is the Head of the University’s School of Biological Sciences, Professor Abigail Fowden (Professor of Perinatal Physiology, Dept of Physiology, Development and Neuroscience). The Institute Administrative Committee is composed of senior Institute members. Our scientific progress and future research plans are assessed at intervals of up to two years by our International Scientific Advisory Board, whose current members are: Dr Judith Kimble (Dept of Biochemistry, University of Wisconsin-Madison) (Chair), Dr Geneviève Almouzni (Institut Curie, Paris), Professor Sir Adrian Bird (Wellcome Trust Centre for Cell Biology, University of Edinburgh), Professor Steve Cohen (University of Copenhagen), Dr Elisabeth Knust (Max Planck Institute of Molecular Cell Biology and Genetics, Dresden), Dr Matthias Peter (ETH Zurich) and Professor Sally Temple (Neural Stem Cell Institute, New York).
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Julie Ahringer
The regulation of chromatin structure and function
How is chromatin regulated during development for correct cell fates and specific transcription? All nuclear events take place in the context of chromatin, the organisation of genomic DNA with histones and hundreds of associated proteins and RNAs. Regulation of the composition and structure of chromatin controls transcription and all other nuclear processes, and is important for cell fate decisions, the expression of cell identity, the maintenance of pluripotency, and the transformation to cancer. We use C. elegans to study chromatin regulation in gene expression and genome organisation in a wholeorganismal context. This model has many advantages: a complement of core chromatin factors very similar to that of humans, a wellannotated genome 30 times smaller than the human genome, efficient high-throughput RNA interference for loss-of-function studies, and well-characterised cell fates. We apply genetics, high-throughput genomics and computational approaches to a range of problems in chromatin biology and transcriptional control, such as genome organisation, promoter and enhancer function, roles of histone modifications, heterochromatin formation and function, and the regulation of chromatin in developmental transitions. Co-workers: Alex Appert, Fanelie Bauer, Chiara Cerrato, Yan Dong, Julia Falo, Csenge Gal, Ni Huang, Jürgen Jänes, Florence Leroy, Alicia McMurchy, Wei Qiang Seow, Przemyslaw Stempor Selected publications: Latorre I et al. (2015) The DREAM complex promotes gene body H2A.Z for target repression. Genes Dev 29: 495–500. Ho JW, modENCODE consortium, et al. (2014) Comparative analysis of metazoan chromatin architecture. Nature 512: 449–452. Chen, A-J et al. (2014) Extreme HOT regions are CpG dense promoters in C. elegans and human. Genome Research 24: 1138–1146.
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Focus on research
DNA
bidirectional transcription
A
TF
bidirectional transcription
TF
RNA Pol II
RNA Pol II
TF T TF
T TF
TF
TF
TF promoter ?
?
promoter gene
gene
enhancers
enhancers Top: Promoters and enhancers are regulatory elements with similar properties. Both bind regulatory factors (TF), initiate bi-directional transcription, and generate long RNAs. How enhancers regulate promoters is poorly understood. Left: Circos plot of a 200 MB region of C. elegans chromosome I. Inner circle shows individual chromatin interactions, which occur at high frequency at regulatory elements. Outer circle shows genes, and other circles show different histone modifications and regulatory elements.
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Andrea Brand How do neural stem cells build and maintain the brain? Discovering how stem cells are maintained, and how their progeny acquire distinct cellular properties, is a key step in developing stem cell therapies. Neural stem cells often exist in a quiescent (non-dividing) state, but can be reactivated in response to changing physiological conditions. Identifying the genetic switches governing stem cell dormancy and proliferation could enable stem cells to be re-awakened to repair the brain after disease or injury.
Stem cells to synapses: self-renewal and differentiation in the nervous system
We are identifying the genes that regulate neural stem cell behaviour using targeted Dam-ID (TaDa), a technique we developed to analyse gene expression in individual cell types in vivo. We found that insulin stimulates stem cell reactivation and division. However, stem cell proliferation must be kept in check, as unconstrained division can lead to tumour formation. We identified a factor, Lola, which maintains neurons in a differentiated state. Without Lola, neurons revert to stem cells and proliferate uncontrollably, forming brain tumours. The ability to induce neurons to dedifferentiate, and then redifferentiate into neurons of choice, would be an ideal method of repair. Co-workers: Neha Agrawal, Janina Ander, Elizabeth Caygill, Seth Cheetham, Melanie Cranston, Abhijit Das, Catherine Davidson, Anna Hakes, Owen Marshall, Stephanie Norwood, Leo Otsuki, Chloe Shard, Christine Turner, Jelle van den Ameele, Mo Zhao Selected publications: Spéder P, Brand AH (2014) Gap junction proteins in the blood–brain barrier control nutrient-dependent reactivation of Drosophila neural stem cells. Dev Cell 30(3): 309–321. Southall TD et al. (2014) Dedifferentiation of neurons precedes tumor formation in Lola mutants. Dev Cell 28(6): 685–696. Southall TD et al. (2013) Cell-type-specific profiling of gene expression and chromatin binding without cell isolation: assaying RNA Pol II occupancy in neural stem cells. Dev Cell 26(1): 101–112.
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Quiescent neural stem cells extend neuron-like projections deep into the central nervous system of Drosophila. Nuclei are stained in red, membranes in green and neuronal synapses in blue.
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Jenny Gallop How do cells generate and maintain their characteristic shapes? The cell membrane, as the boundary of the cell, is moulded into shape by dynamic remodelling of its links to the actin cytoskeleton during cell division, polarisation, movement, differentiation and for everyday housekeeping. In disease, the actin machinery is hijacked by invading pathogens. Some actin regulators are overexpressed and redeployed during cancer metastasis, and control of the actin cytoskeleton can be disrupted in genetic diseases, causing intellectual disability, kidney dysfunction and other problems.
Membranes, actin and morphogenesis
We are studying how actin filaments polymerise at two types of specialised structures at the cell membrane: filopodia, which are fingerlike protrusions, and endocytic vesicles, which bud inwards to bring in components from the membrane or environment. We have developed model systems using phospholipid bilayers and frog egg extracts that allow us to follow the molecular events of actin self-assembly in different contexts. By focusing on unusual predictions from these in vitro assays, we work out how the actin cytoskeleton is regulated by imaging cells in accessible, native developmental contexts in fruit fly and frog embryos. Co-workers: Frédéric Daste, Ulrich Dobramysl, Helen Fox, Jonathan Gadsby, Iris Jarsch, Julia Mason, Benjamin Richier, Hanae Shimo, Vasja Urbančič Selected publications: Walrant A et al. (2015) Triggering actin polymerization in Xenopus egg extracts from phosphoinositide-containing lipid bilayers. Methods Cell Biol 128: 125– 147. Gallop JL et al. (2013) Phosphoinositides and membrane curvature switch the mode of actin polymerization via selective recruitment of toca-1 and Snx9. Proc Natl Acad Sci 110: 7193–7198. Lee K et al. (2010) Self-assembly of filopodia-like structures on supported lipid bilayers. Science 329: 1341–1345.
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Actin-based filopodia-like structures (pink) emerging from a phospholipid bilayer (blue) in our in vitro system (fluorescent 3D reconstruction of a two-channel spinning disk confocal microscope z-stack).
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John Gurdon Can we make cell reprogramming more efficient? When a sperm nucleus enters the egg at fertilisation, factors in the egg cytoplasm initiate a sequence of gene expression events from the combined egg and sperm DNA that kick-start development of a new organism. When the nucleus of a mature body cell is transplanted to an egg, it is similarly induced to change its pattern of gene expression to that of an embryo. Yet most body cells resist making this change, while almost all sperm nuclei are successfully reprogrammed.
Nuclear reprogramming by oocytes and eggs
Our research aims to characterise the fine details of cell reprogramming: how the oocyte reprogrammes a cell nucleus. Equally importantly, we want to know what mechanisms ensure the remarkable stability of normal cell differentiation and its resistance to reprogramming by eggs. We use a variety of techniques for manipulating gene expression before maternal reprogramming factors become active in defolliculated oocytes, including: adding different transcription factors, chromatin fractionation, over- and underexpressing messenger RNA and mutating donor nuclei. Co-workers: David Aziz Alaoui, Dilly Bradford, Nigel Garrett, Eva Hoermanseder, Jerome Jullien, Magda Koziol, Angela Simeone, Ferenc Tajti, Munender Vodnala, Ming-Hsuan Wen Selected publications: Jullien J et al. (2014) Hierarchical molecular events driven by oocyte-specific factors lead to rapid and extensive reprogramming. Molecular Cell 55: 1–13. Miyamoto K et al. (2013) Nuclear WAVE1 is required for reprogramming transcription in oocytes and for normal development. Science 341: 1002– 1005. Jullien J et al. (2011) Mechanisms of nuclear reprogramming by eggs and oocytes: a deterministic process? Nature Revs Molecular & Cell Biology 12: 453-459.
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Developmental mechanisms egg nuclear transfer
muscle cell Reprogramming mechanisms oocyte (= egg progenitor)
TF mRNA
manipulate different transcription factors ∙ chromatin fractionation ∙ mutate donor nuclei ∙ over/under-express mRNA ∙ 0h
follow effects on reprogramming ∙ protein/RNA expression ∙ ChIP seq. ∙ chromatin composition ∙ etc. 72h
somatic Pol II TBP somatic gene repression histone B4 binding TBP2 Pol II binding Ser5P Pol II Ser2P Pol II
Experimental design for studying nuclear reprogramming mechanisms in the oocyte, and some of our results on changes in nuclear events.
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Martin Hemberg What can sequencing data tell us about disease? To create the different cell types in an organism, different genes are expressed at different times from the whole genome as transcripts of RNA, which will include both protein-coding and non-coding species. Understanding how, why, when and where genes are expressed is crucial for understanding not just development but also many diseases. High-throughput sequencing of RNA from different tissues can now provide insights into gene expression and related properties, but the experimental datasets are large, high-dimensional and noisy. Computational methods are required to extract maximum information from such data.
Computational analyses of large genomic datasets
Our group uses computational analysis to develop quantitative models of gene expression and gene regulation. In particular, we are exploring single-cell RNA sequencing, which can reveal insights that are inaccessible through traditional bulk experiments; for example, to estimate the number of differentiated cell types in the body. Another strand of research aims to further our understanding of noncoding DNA – providing better models of regulatory elements and characterising non-coding RNA. Co-workers: Tallulah Andrews, Ilias Georgakopolous-Soares, Vladimir Kiselev, Guillermo Parada (all Wellcome Trust Sanger Institute) Selected publications: Kiselev VY et al. (2016) SC3 - consensus clustering of single-cell RNA-Seq data. BiorXiv pre-print at http://dx.doi.org/10.1101/036558. Prabakaran S et al. (2014) Quantitative profiling of peptides from RNAs classified as noncoding. Nature Communications 5: 5429. Kim TK et al. (2010) Widespread transcription at neuronal activity-regulated enhancers. Nature 465 (7295): 182–187.
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Genes
N Cells
Distances
Transformations
Euclidean
PCA
d range d1 d2
Spectral Gene filter
d3 ... dD
PCA
Pearson
Spectral Spearman
d
PCA Spectral
+ ... +
+
0
k-means
Consensus
Labels(1,d1) Labels(1,d2) Labels(1,d3) ... Labels(1,dD) Labels(i,d1) Labels(i,d2) Labels(i,d3) ... Labels(i,dD)
Consensus Labels
Labels(6,d1) Labels(6,d2) Labels(6,d3) ... Labels(6,dD)
0,2 0,4 0,6 0,8 1
+
=
Starting with single-cell RNA sequence analysis, we apply a computational method that clusters cells showing similar patterns in the sequence data, such that each cluster may represent a different type of cell. Our method, SC3 (unsupervised single-cell consensus clustering), is interactive and provides a robust clustering by combining a large number of outcomes obtained by using different parameters.
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Meritxell Huch How can we repair diseased liver and pancreas? In adult mammals, many tissues have the capacity to self-renew to maintain healthy function and after damage. But the capacity for cell turnover varies. In the intestine and stomach, adult stem cell populations are constantly replenishing, while in the liver and pancreas cell proliferation is limited. Chronic liver disease and pancreatic cancer are strongly associated with inflammation and tissue damage, which activates stem cells and progenitor cells to repair lost tissue. Our goal is to understand the activation mechanism in order to harness it for therapeutic strategies.
Stem cells and tissue regeneration in liver and pancreas
We have established a novel culture system for liver organoids, which allows the massive and infinite expansion of mouse liver cells into three-dimensional structures that resemble functional liver tissue. When transplanted into a mouse model of liver disease (‘FAH –/–’), these cells partially rescued the liver phenotype. We also work with pancreas cells and diseased human liver cells in culture, and are testing how well our models can represent in vivo pathology. Co-workers: Luigi Aloia, Robert Arnes, Laura Broutier, Lucia Cordero Espinoza, John Crang, Berta Font Cunill, Daisy Harrison, Christopher Hindley, Nicolas Hircq, Gianmarco Mastrogiovanni, Mikel McKie, Cora Olpe Selected publications: Huch M and Koo BK (2015) Modeling mouse and human development using organoid cultures. Development 142(18): 3113–3125. Boj SF et al. (2015) Organoid models of human and mouse ductal pancreatic cancer. Cell 160(1–2): 324–338. Huch M et al. (2015) Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 160(1–2): 299–312.
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Mouse liver organoid (about 100Âľm across) showing three types of cells: differentiated hepatocytes (marked by Albumin, red), cholangiocytes (expressing Krt19, purple) and epithelial cells (marked with the protein ZO-1, green). Hepatocytes perform numerous metabolic functions and secrete bile in the whole liver, but are very difficult to grow in culture. Our organoids therefore represent an expandable source of liver cells for in vitro experiments.
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Steve Jackson Can we alleviate disease by targeting DNA repair? The DNA in our cells constantly receives insults from natural radiation, sunlight, chemicals and cell metabolism, leading to DNA breaks and potential disruption of genome integrity and gene expression. Cell survival and genome integrity are supported by a series of events, the DNAdamage response (DDR), which detect, signal the presence of, and then mediate DNA repair. Defects in the DDR are associated with a wide variety of conditions including developmental disorders, immunodeficiencies, infertility, premature ageing and cancer.
Maintenance of genome stability
Our research continues to characterise the cell biology of DDR pathways to discover new therapeutic strategies, using yeast and mammalian cells in culture. We aim to identify important DDR proteins, and their functions, regulation and roles in diverse cellular events. For example, we recently developed a new screening technique to find enzymes that modify DDR protein activity, focusing on the many cellular proteins involved in ubiquitylation/deubiquitylation. We are also exploring the concepts of synthetic lethality and synthetic viability to identify novel therapeutic targets for a range of human diseases. Co-workers: Carmen Adriaens, Pallavi Agarwal, Gabriel Balmus, Linda Baskcomb, Rimma Belotserkovskaya, Andy Blackford, Serena Bologna, Ting-Wei Chiang, Julia Coates, Matt Cornwell, Muku Demir, Gopal Dhondalay, Kate Dry, Ana Fernandes de Sousa Barros, Josep Forment, Yaron Galanty, Nicola Geisler, Mareike Herzog, Delphine Larrieu, Donna Lowe, Natalia Lukashchuk, Francisco Muñoz Martinez, Fabio Puddu, Helen Reed, Israel Salguero Corbacho, Christine Schmidt, Matylda Sczaniecka-Clift, Alexandra (Sasha) Selivanova, Ann-Marie Shorrocks, Rohan Sivapalan, Siyue Wang, Paul Wijnhoven Selected publications: Schmidt CK et al. (2015) Systematic E2 screening reveals a UBE2D–RNF138– CtIP axis promoting DNA repair. Nature Cell Biology 17: 1458–1470. Ochi T et al. (2015) PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair. Science 347: 185–188.
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Circos plot adaptation illustrating complex connections between ~40 human ubiquitin E2 enzymes and their cellular responses to DNA double-strand breaks. These connections, also termed ribbons, can be used as a platform to identify E2–E3–substrate axes within the DNA damage response.
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Tony Kouzarides Do chromatin and RNA modifications offer therapeutic targets? DNA exists in the cell nucleus wrapped around histone proteins to form chromatin, a structure that must be navigated by the transcriptional machinery in order to ‘read’ the genetic code. The DNA and histones are decorated with many types of covalent chemical modifications, which can affect transcription and other cellular processes. In addition, non-coding RNAs that regulate chromatin function can be similarly chemically modified. Our lab is involved in characterising the pathways that mediate DNA, RNA and histone modifications. We try to understand the cellular processes they regulate, their mechanism of action and their involvement in cancer.
Epigenetic modifications and cancer
We recently identified a novel modification of histones, methylation of glutamine, and showed that it regulates transcription; a different histone modification, citrullination, was shown to have a role in pluripotency; a novel RNA methyltransferase (BCDIN3D) was shown to be involved in cancer; and a small-molecule epigenetic inhibitor, I-BET, was shown to displace BET proteins from leukaemia genes and to be effective against MLL-leukaemia. I-BET is currently in clinical trials. Co-workers: Andrej Alendar, Paulo Amaral, Andrew Bannister, Isaia Barbieri, Ester Cannizzaro, Ka Hing (Harvey) Che, Alistair Cook, Namshik Han, Sri Lestari, Nikki Mann, Carlos Melo, Valentina Migliori, Gonzalo Millan Zambrano, Luca Pandolfini, Sam Robson, Helena Santos Rosa, Meike Wiese Selected publications: Tessarz P et al. (2014) Glutamine methylation in histone H2A is an RNApolymerase-I-dedicated modification. Nature 505(7484): 564–568. Christophorou MA et al. (2014) Citrullination regulates pluripotency and histone H1 binding to chromatin. Nature 507(7490): 104–108. Dawson MA et al. (2011) Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature 478(7370): 529–533.
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enzyme
enzym enzyme read reader mod
histone
RNA
readerr mod
enzyme
DNA
reader mod
Normal epigenetic regulation
Epigenetic misregulation in cancer
Chemical modifications that regulate different aspects of gene expression have been identified on DNA and histone proteins within chromatin, as well as on non-coding RNAs. We aim to identify and characterise the modifications, the enzymes that catalyse modification reactions and the transcription machinery that recognises the modifications, to yield new strategies for cancer therapeutics.
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Rick Livesey
Development, evolution and degeneration of the brain
Can we model human brain development and disease in the lab? The human cerebral cortex, the thinking, decision-making, largest part of our brain, sets us apart from other animals – and poses a challenge for biomedical researchers. Animal models cannot capture the spectrum of characteristics of the human cerebral cortex in development or disease, and so our research uses human cells in tissue culture. Our methods for differentiating human pluripotent stem cells – via cortical stem cells – into cortical neurons allows us to study neurons and the neural circuits they make, starting from living patients’ cells. We are studying how the human cerebral cortex develops and how that differs from other animals, and how variations in development lead to disease. We also apply these approaches to study neurodegeneration in dementia, particularly Alzheimer’s disease. Using stem cells from patients with genetic forms of Alzheimer’s disease, we have modelled the disease pathogenesis in neurons in culture. We use these systems to understand how Alzheimer’s disease starts and progresses in the brain, and to test the efficacy of potential therapeutic strategies. Co-workers: Philipp Berg, Phil Brownjohn, Katherine Dudman, Lewis Evans, Jayne Fisher, Alberto Frangini, Ayiba Momoh, Steven Moore, Benjamin Ng, Tomoki Otani, Francesco Paonessa, Manuel Peter, James Smith, Ravi Solanki, Alessio Strano, Vickie Stubbs, Ellie Tuck Selected publications: Moore S et al. (2015) APP Metabolism Regulates Tau Proteostasis in Human Cerebral Cortex Neurons. Cell Reports 11(5): 689–696. Kirwan P et al. (2015) Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro. Development 142(18): 3178–3187.
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Human cortical neurons that have been generated in the lab from pluripotent stem cells and grown in tissue culture for 250 days. The interconnected mass of neurons is stained for the microtubule marker MAP2 (red) and the TAU protein (green), which plays an important role in Alzheimer’s disease.
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Eric Miska What does non-coding RNA do in development and disease? Most of the RNA transcribed from the DNA in our genome is not translated into protein but instead has direct functions in regulating biological processes. This paradigm shift in nucleic acid biology has been supported by technical advances in high-throughput sequencing, molecular genetics and computational biology, which can be combined with more traditional biochemical analyses.
Non-coding RNA and genome dynamics
Many species and roles of non-coding RNA have been identified. Our goal is to understand how non-coding RNAs regulate development, physiology and disease. We are exploring microRNA in the pathology of cancer and other diseases, RNA interference in viral immunity, Piwiinteracting RNA in germline development and genome integrity, and endogenous small interfering RNA in epigenetic inheritance – where we predict a big impact in understanding human health. Our model organisms are the nematode worm, mouse and human cell culture. More recently we have started using comparative genomics and denovo genome sequencing of African cichlid fish to unravel the role of non-coding RNA in evolution. Co-workers: Alper Akay, Parsa Akbari, André Nicolau Aquime Gonçalves, Ahmet Can Berkyurek, Fabian Braukmann, Isabela Cunha Navarro, Tomas Di Domenico, Benjamin Fisher, Lise Frezal, Katharina Gapp, Tanay Ghosh, Sabrina Huber, David Jordan, Joanna Kosalka, Miranda Landgraf, Jérémie le Pen, Milan Malinsky, Eyal Maori, Wayo Matsushima, Guillermo Parada Gonzalez, Marc Ridyard, Alexandra Sapetschnig, Lalana Songra, Kin Man Suen, Mélanie Tanguy, Gregoire Vernaz, Omer Ziv Selected publications: Malinsky M et al. (2015) Genomic islands of speciation separate cichlid ecomorphs in an East African crater lake. Science 350(6267): 1493–1498. Ashe A et al. (2015) Antiviral RNA Interference against Orsay Virus Is neither Systemic nor Transgenerational in Caenorhabditis elegans. J Virol 89(23): 12035–12046. Gapp K et al. (2014) Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nat Neuroscience 17(5): 667–669.
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Total length (mm)
160 120 80
eigenvector 2 1.63% of observed genetic variation
40 -0.08 -0.04 0 0.04 0.08 Principal component axis 1 (29.7% of shape variation)
0.2 0.1 -0.0 -0.1 -0.2 -0.3 -0.15 -0.10 -0.05 0.00 0.05 0.10 0.15 0.20 eigenvector 1 3.31% of observed genetic variation
Top: Morphological divergence between two cichlid fish ecomorphs of Lake Massoko, Tanzania, measured by length of head and jaw. Bottom: Statistical analysis of whole-genome DNA sequences separates the Lake Massoko cichlids into genetic clusters corresponding to morphology.
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Eugenia Piddini Can we learn how to exploit cell competition to design new therapies? Competitive interactions occur between cells in tissues, resulting in fit cells (winners) being able to colonise tissues as they kill and replace less-fit cells (losers). We are exploring how cell competition could be harnessed for therapeutic strategies in regenerative medicine and cancer. Towards that aim, our goal is to understand the impact of cell competition on tissues and the mechanisms that cells use to compete. We combine two complementary approaches: studies in Drosophila to capture the complexity of these interactions in vivo, and mammalian cell culture to follow the dynamics of cell competition, including by live imaging.
Cell competition in normal physiology and cancer
Our recent work using the adult fly intestine shows that in adult homeostatic tissues, cells compete and healthy cells eliminate subfit cells by apoptosis. Conversely, we found that cell competition leads to healthy tissue expansion, by promoting stem cell proliferation and increased symmetric self-renewal. We believe that this could be exploited to promote stem cell repopulation in regenerative medicine therapies. Co-workers: Michael Dinan, Maja Goschorska, Anna Klucnika, Golnar Kolahgar, Kasia Kozyrska, Iwo Kucinski, Tom Newman, Kathy Oswald, Yasmin Paterson, Laura Wagstaff Selected publications: Kolahgar G et al. (2015) Cell competition modifies adult stem cell and tissue population dynamics in a JAK-STAT dependent manner. Dev Cell 34(3): 297–309. Graml V et al. (2014) A genomic multi-process survey of the machineries that control and link cell shape, microtubule organisation and cell cycle progression. Dev Cell 31(2): 227–239. Wagstaff L et al. (2013) Competitive cell interactions in cancer: a cellular tug of war. Trends Cell Biol 23(4): 160–167.
28 Focus on research
What are the mechanisms of cell competition? What is the impact of cell competition on adult tissues?
Do cancer ce cells engage in umour–host cell ce tumour–host mpetition and does do competition is promote their the this growth?
Can we harness cell competition for therapeutic strategies?
During cell competition, unhealthy cells are eliminated from tissues by interaction with fitter cells.
The Gurdon Institute
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Emma Rawlins How do stem cells build and maintain the lung? The complicated three-dimensional structure of our lungs is essential for respiration and host defence. Building this structure relies on the correct sequence of division and differentiation events by lung progenitor cells, which also maintain the slowly turning-over airway epithelium in the adult. How is the production of different cell types controlled in embryonic development and adult maintenance? We apply mouse genetics, live imaging, single-cell molecular analysis and mathematical modelling to understand lung stem cells, with a longer-term aim of directing endogenous lung cells to repair diseased tissue.
Stem and progenitor cells in the mammalian lung
In the embryonic lung we have identified a population of multipotent epithelial progenitors, which undergo a steroid-induced change in competence and gene expression during embryogenesis. Our recent work in the adult mouse tracheal epithelium uncovered two morphologically identical subpopulations of basal cells: stem cells and long-lived precursors that are already committed to differentiation. We are now exploring how to grow lung epithelial stem cells as self-renewing organoids, and the mechanisms that maintain adult quiescence. Co-workers: Jane Brady, Jo-Anne Johnson, Florence Leroy, Marko Nikolic, Dawei Sun Selected publications: Watson JK et al. (2015) Clonal Dynamics Reveal Two Distinct Populations of Basal Cells in Slow Turnover Airway Epithelium. Cell Reports 12(1): 90–101. Rawlins EL et al. (2009) The role of Scgb1a1+ Clara cells in the long-term maintenance and repair of lung airway, but not alveolar, epithelium. Cell Stem Cell 4(6): 525–534. Rawlins EL et al. (2009) The Id2+ distal tip lung epithelium contains individual multipotent embryonic progenitor cells. Development 136 (22): 3741–3745.
30 Focus on research
These lung epithelium organoids have been grown from the lungs of a human 42-day embryo. They have been maintained in tissue culture for 22 weeks with a cocktail of factors that supports self-renewal and expansion. We have therefore multiplied the amount of experimental material that can be derived from the original sample. We use this model system to examine molecular and cellular mechanisms of human lung differentiation and how this can go wrong in disease.
The Gurdon Institute
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Ben Simons How do stem cells regulate fate behaviour to specify and maintain tissues? Stem cells are defined by their capacity to self-renew while giving rise to differentiating progeny. In development, the balance between proliferation and differentiation must be controlled to specify tissues of the correct size, patterning and composition. In the adult, stem cells must achieve a perfect balance between proliferation and differentiation to achieve homeostasis.
Mechanisms of stem cell fate in development, homeostasis and disease
To address the mechanisms that regulate stem cell fate we combine genetic lineage tracing and in vivo live-imaging approaches with methods from statistical physics. Applied to epithelial tissues including epidermis, intestine and testis, our studies have shown that stem cells are not individually long-lived, but are constantly lost and replaced. Further, stem cells are not invariant, but may transit reversibly between states poised for renewal or primed for differentiation. As well as questioning stem cell identity and the mechanisms that underpin cell heterogeneity and flexibility, these studies establish a quantitative platform to explore pathways leading to tumour initiation and progression. Co-workers: Juergen Fink (Stem Cell Institute), Phillip Greulich, Edouard Hannezo, Chris Hindley, David Jorg, Crystal McClain (Stem Cell Institute), Steffen Rulands, Magdalena Sznurkowska (Dept of Oncology), Julia Tischler Selected publications: Chabab S et al. (2016) Uncovering the Number and Clonal Dynamics of Mesp1 Progenitors during Heart Morphogenesis. Cell Reports 14(1): 1–10. Gao P et al. (2014) Deterministic progenitor behavior and unitary neuron production in the neocortex. Cell 159: 775–788. Ritsma L et al. (2014) Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging. Nature 507: 362–365.
32 Focus on research
Mosaic labelling of the developing mouse heart at embryonic day 12.5 using a multicolour lineage labelling system that marks Mesp1-expressing cardiac cell precursors at embryonic day 7. The individual clusters of cells indicate the progeny of single Mesp1-expressing cells. Quantitative analysis of these clusters show that Mesp1 expression marks the earliest stage of lineage commitment to the first and second heart field.
The Gurdon Institute
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Daniel St Johnston How do cells know ‘up’ from ‘down’? Normal cells in the body are not symmetrical spheres; most take up specialised shapes and perform different functions at opposite ‘ends’. Cell polarity is also essential in development, for example in determining the head-to-tail axis of many animals, for cell migration and for asymmetric stem-cell divisions to supply specialised daughter cells. Furthermore, loss of polarity is a hallmark of tumour cells and is thought to contribute to tissue invasion and metastasis.
Polarising epithelial cells and body axes
We explore polarity in Drosophila and in mouse intestinal organoids. Much of our work focuses on epithelia, the sheets of polarised cells that make up most organs of the body to form barriers between compartments. We study the factors that mark different sides of the cell and how these organise the internal cell architecture. For example, we have determined how cells divide so that both daughters stay in the epithelial layer, and have found a mechanism that pulls cells born outside the monolayer back into place. Now we are using live superresolution microscopy to visualise polarised transport in epithelial cells. Co-workers: Edward Allgeyer, Dan Bergstralh, Alisha Burman, Catia Carvalho Mendes, Jia Chen, Nicole Dawney, Hélène Doerflinger, Edo Dzafic, Weronika Fic, Jacqueline Hall, Holly Lovegrove, Nick Lowe, Avik Mukherjee, Dmitry Nashchekin, John Overton, Andrew Plygawko, Amy Reynolds, Artur Ribeiro Fernandes, Jenny Richens, George Sirinakis, Vanessa Stefanak, Vitor Trovisco, Helen Zenner Selected publications: Bergstralh DT et al. (2015) Lateral adhesion drives reintegration of misplaced cells into epithelial monolayers. Nat Cell Biol 7(11): 1497–1503. Khuc Trong P et al. (2015) Cortical microtubule nucleation can organise the cytoskeleton of Drosophila oocytes to define the anteroposterior axis. Elife 4. 10.7554/eLife.06088. St Johnston D (2015) The renaissance of developmental biology. PLoS Biol doi: 10.1371/journal.pbio.1002149.
34 Focus on research
A Drosophila egg chamber showing a large clone of mutant epithelial cells, marked by the loss of GFP (green), that cannot reintegrate into the monolayer after they have divided with the wrong orientation.
The Gurdon Institute
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Azim Surani What makes a germline cell? We study primordial germ cells (PGCs), precursors to eggs and sperm, in the early embryo. We have established principles for the mechanisms of cell fate determination and epigenetic programming that are widely applicable to human development and disease. Our work on PGC specification shows that SOX17 is the key regulator of human, but not mouse, germ cell fate. By developing an in vitro model, and with authentic hPGCs from human embryos, we have also established how pluripotent cells gain competence for germ cell fate in human, compared with mouse. These studies reveal important differences between mouse and human development that might impact on other early cell fate decisions.
Human germ cell specification and epigenetic programming
Whereas SOX17–BLIMP1 apparently initiate the epigenetic programme in early human germline, BLIMP1– PRDM14 play a similar role in mouse germline, resulting in the comprehensive erasure of DNA methylation (except for some resistant loci), X-reactivation and imprints erasure, followed by re-establishment of sperm and oocyte-specific imprints. Because these imprints are gamete-specific and inherited by the subsequent generation, they provide a model for how different sets of epigenetic marks affect the same genome, to result in different patterns of gene expression and development. Co-workers: Maud Borensztein, Dang Vinh Do, Lynn Froggett, Wolfram Gruhn, Ufuk Günesdogan, Jamie Hackett, Yun Huang, Naoko Irie, Elena Itskovich, Shinseog Kim, Toshihiro Kobayashi, Caroline Lee, Chris Penfold, Navin Brian Ramakrishna, Anastasiya Sybirna, Walfred Tang, Julia Tischler, Frederick Wong Selected publications: Murakami K et al. (2016) NANOG alone induces germ cells in primed epiblast in vitro by activation of enhancers. Nature 529: 403–407. Tang WWC et al. (2015) A Unique Gene Regulatory Network Resets the Human Germline Epigenome for Development. Cell 161(6): 1453–1467. Irie N et al. (2015) SOX17 Is a Critical Specifier of Human Primordial Germ Cell Fate. Cell 160(1–2): 253–268.
36 Focus on research
epiblast in egg cylinder
BLIMP1—PRDM14
primordial germ cells (PGCs)
SOX17—BLIMP1
PGC specification
postimplantation development
primordial germ cells (PGCs)
epiblast in bilaminar embryonic disc postimplantation development
blastocyst mouse
human
zygote epigenetic resetting in germline
epigenetic resetting in germline gametes
There are differences in postimplantation embryonic development between mouse and human (egg cylinder versus bilaminar disc). Our work has now uncovered differences in the genetic regulation of mouse and human primordial germ cell specification.
The Gurdon Institute
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Philip Zegerman How is DNA replication controlled? A fundamental requirement for all life on earth is that an exact copy of the entire genome must be made before cell division. DNA replication is therefore tightly regulated because failures in this process cause genomic instability, which is a hallmark of many diseases, most notably cancers. In addition, inhibition of DNA replication is the primary mode of action of many anti-tumour therapies. Therefore investigating DNA replication control is important for finding new ways to diagnose and treat cancers. The evolutionary conservation of DNA replication mechanisms allows us to study this process in multiple systems, facilitating the translation of findings to humans.
The regulation of DNA replication initiation in eukaryotes
We have shown that the levels of several key replication factors are critical to control the rate of genome duplication, not only in the single-celled organism, budding yeast, but also during vertebrate development in frog embryos. Our studies demonstrate that regulation of the levels of these factors is vital not only for normal cell division, but also for regulating the rate of cell proliferation in animal tissue. This has important implications for the deregulation of cell proliferation, which occurs in cancers. Co-workers: Geylani Can, Clara Collart, Vincent Gaggioli, Christine Hänni, Fiona Jenkinson, Mark Johnson, Barbara Schöpf Selected publications: Gaggioli V et al. (2014) CDK phosphorylation of SLD-2 is required for replication initiation and germline development in C. elegans. J Cell Biol 204(4): 507–522. Collart C et al. (2013) Titration of four replication factors is essential for the Xenopus laevis midblastula transition. Science 341(6148): 893–896. Mantiero D et al. (2011) Limiting replication initiation factors execute the temporal programme of origin firing in budding yeast. EMBO J 30(23): 4805– 4814.
38 Focus on research
origin of replication
two fully replicated DNA strands ready for cell division
incomplete replication
replication initiation happens more than once before cell division mutation
Regulation of replication initiation is critical for normal cell division.
The Gurdon Institute
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Alex Sossick Providing access to state-of-the-art microscopy, to enable front-line research in cell and developmental biology. The Imaging Facility is a very popular service for Institute researchers, with over 100 different people using the facility monthly, and almost 200 unique users annually. One of our key roles is to provide advice and training, from basic microscopy through to advanced techniques. We support a wide array of imaging techniques, from wide-field deconvolution microscopes and confocal microscopes to super-resolution microscopy.
Gurdon Institute Imaging Facility
Currently the facility has four confocal microscopes, all equipped with a full range of lasers and sensitive detectors. We continually upgrade these with new features. Current upgrades include Fluorescence Correlation Spectroscopy, a second scanner for DNA damage and a super-resolution module. We also have a spinning-disk confocal microscope capable of two-colour full-frame imaging at 65 frames per second. In addition to two wide-field microscopes, we have a superresolution structured illumination microscope. Image processing is an essential part of any imaging experiment, and is commonly used to improve the signal-to-noise ratio and extract quantitative information from biological image data. The Imaging Facility team can assist with finding appropriate tools and writing custom software to meet the specific requirements of any imaging project. Co-workers: Nicola Lawrence, Richard Butler Selected publications: Murakami K et al. (2016) NANOG alone induces germ cells in primed epiblast in vitro by activation of enhancers. Nature 529: 403–407. Vowinckel J et al. (2015) MitoLoc: A method for the simultaneous quantification of mitochondrial network morphology and membrane potential in single cells. Mitochondrion 24: 77–86. Campbell K et al. (2015) Self-establishing communities enable cooperative metabolite exchange in a eukaryote. eLife 4:e09943.
40 Focus on research
5 Îźm
Orthogonal view of the surface of the Drosophila brain, captured using a structured illumination microscope. Blood–brain barrier in red and extracellular matrix protein in green. Sample prepared by Jun Liu and Andrea Brand.
The Gurdon Institute
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The Gurdon Institute in 2015: People SENIOR GROUP LEADERS DANIEL ST JOHNSTON PhD FRS FMedSci, Director Wellcome Trust Principal Research Fellow; Professor of Developmental Genetics; Member, European Molecular Biology Organization; Director, Company of Biologists; (Member of the Department of Genetics) HÉLÈNE DOERFLINGER PhD Wellcome Trust Research Associate/ Institute Public Engagement Officer ARTUR FERNANDES MPhil School of Biological Sciences PhD Student DAN BERGSTRALH PhD Wellcome Trust Research Associate CATIA ALEXANDRA CARVALHO MENDES MSc Fundação para a Ciência e Tecnologia (FCT) PhD Student JIA CHEN PhD Wellcome Trust Research Associate NICOLE DAWNEY BSc Wellcome Trust Research Assistant
WERONIKA FIC PhD Wellcome Trust Research Associate JACKIE HALL MSc Wellcome Trust Senior Research Technician HOLLY LOVEGROVE MSc Herchel Smith PhD Student NICK LOWE PhD Wellcome Trust Research Associate AVIK MUKHERJEE MSc CISS PhD Student
DMITRY NASHCHEKIN PhD Wellcome Trust Research Associate ANDREW PLYGAWKO MSc Herchel Smith PhD Student JENNIFER RICHENS PhD Wellcome Trust Research Associate GEORGE SIRINAKIS PhD Wellcome Trust Senior Research Associate VANESSA STEFANAK PhD Administration Manager for the Office of the Director VITOR TROVISCO PhD Wellcome Trust Research Associate HELEN ZENNER-BRANCO PhD Wellcome Trust Research Associate
JULIE AHRINGER PhD FMedSci Professor of Genetics and Genomics; Wellcome Trust Senior Research Fellow; Member, European Molecular Biology Organization; (Member of the Department of Genetics) ALEX APPERT PhD Wellcome Trust Research Associate
CHIARA CERRATO MSc Wellcome Trust Research Assistant
EMMA BALL PA/Secretary
RON CHEN PhD Wellcome Trust Senior Research Associate
FANÉLIE BAUER PhD Herchel Smith Fellow
ITALICS = Leavers in 2015
42 People in 2015
YAN DONG MSc Wellcome Trust Research Associate CSENGE GAL PhD Wellcome Trust Research Associate CAROLINA GEMMA PhD Wellcome Trust Research Associate NI HUANG PhD Wellcome Trust Research Associate (Bioinformatics)
JÜRGEN JÄNES MSc Wellcome Trust Mathematical Biology PhD Student FLORENCE LEROY MA PA/Secretary ALICIA McMURCHY PhD CIHR Research Associate WEI QIANG SEOW BSc A*STAR PhD Student
PRZEMYSLAW STEMPOR PhD Wellcome Trust Research Associate ANNETTE STEWARD BSc Wellcome Trust Research Assistant CHRISTINE TURNER PA/Secretary CARSON WOODBURY BA Thouron Scholar MPhil Student BRIAN WYSOLMERSKI BA MPhil Student
ANDREA BRAND PhD FRS FMedSci Herchel Smith Professor of Molecular Biology; Head of Wellcome Trust Labs; Wellcome Trust Senior Investigator; Member of Council, The Royal Society; Member, European Molecular Biology Organization; (Member of the Department of Physiology, Development and Neuroscience) MELANIE CRANSTON BA BBSRC Research Assistant ABHIJIT DAS PhD Wellcome Trust Research Associate CATHERINE DAVIDSON BSc BBSRC Research Associate NEHA AGRAWAL PhD Wellcome Trust Research Associate JANINA ANDER BSc BBSRC PhD Student JOSEPHINE BAGERITZ PhD Wellcome Trust Research Associate ELIZABETH CAYGILL PhD BBSRC Reseach Associate SETH CHEETHAM BSc Herchel Smith PhD Student
PAUL FOX PhD Wellcome Trust Research Associate ANNA HAKES MPhil Wellcome Trust Developmental Mechanisms PhD Student JUN LIU BA Dr Herchel Smith Graduate Fellow OWEN MARSHALL PhD BBSRC Research Associate STEPHANIE NORWOOD MRes BBSRC PhD Student
LEO OTSUKI MPhil Wellcome Trust Developmental Mechanisms PhD Student CHLOE SHARD BSc Australia Trust/McCrum/Cambridge Commonwealth European & International Trust PhD Student PAULINE SPÉDER PhD Wellcome Trust Research Associate CHRISTINE TURNER PA/Secretary JELLE VAN DEN AMEELE MD PhD EMBO Research Fellow/Wellcome Trust Postdoctoral Clinical Fellow MO ZHAO BSc Chinese Scholarship Council PhD Student
NICK BROWN PhD Professor of Cell Biology; Member, European Molecular Biology Organization; (Member of the Department of Physiology, Development and Neuroscience) NATALIA BULGAKOVA PhD BBSRC Research Associate JUAN MANUEL GOMEZ PhD BBSRC Reseach Associate
HANNAH GREEN MPhil Wellcome Trust Developmental Mechanisms PhD Student
BENJAMIN KLAPHOLZ PhD BBSRC Research Associate TARUN KUMAR BSc Commonwealth PhD Student
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MIRANDA LANDGRAF MA PA/Secretary
PEERAPAT THONGNUEK MRes Thai Government PhD Student
AIDAN MAARTENS PhD BBSRC Research Associate
THOMAS VOLATIER MSc MPhil Student
JOHN OVERTON HNC Wellcome Trust/BBSRC Chief Research Technician
EMMA WICTOME BA BBSRC Research Assistant
JOHN GURDON Kt DPhil DSc FRS Distinguished Group Leader; Nobel Laureate in Physiology or Medicine 2012; Wellcome Trust Senior Investigator; Foreign Associate, US National Academy of Sciences; Foreign Associate, US National Academy of Sciences Institute of Medicine; Foreign Associate, French National Academy of Sciences; Member, European Molecular Biology Organization; Member, Academia Europaea; Honorary Fellow, Royal College of Physicians; Foreign Member of American Anatomical Society; Honorary Fellow of Anatomical Society of Great Britain; Honorary Fellow UK Academy of Medical Sciences; (Member of the Department of Zoology) EVA HÖRMANSEDER PhD EMBO Research Fellow/Wellcome Trust/Newton Trust Research Associate JEROME JULLIEN PhD Wellcome Trust Research Associate DILLY BRADFORD PA/Secretary NIGEL GARRETT HNC Wellcome Trust Research Assistant
MAGDALENA KOZIOL PhD Wellcome Trust/BBSRC Research Associate KEI MIYAMOTO PhD Herchel Smith Research Associate
MAMI OIKAWA PhD MRC Research Associate ANGELA SIMEONE PhD Wellcome Trust/MRC/BBSRC Research Associate (Bioinformatics) MUNENDER VODNALA PhD Swedish Society for Medical Research (SSMF) Fellow MING-HSUAN WEN MSc Taiwan Government PhD Student
STEVE JACKSON PhD FRS FMedSci Frederick James Quick Professor of Biology; Head of Cancer Research UK Labs; Member, European Molecular Biology Organization; ERC Advanced Researcher; Associate Faculty Member of the Wellcome Trust Sanger Institute; (Member of the Department of Biochemistry) GABRIEL BALMUS DVM PhD Cancer Research UK Research Associate ANA CAMILA BARROS MSc ERC Research Technician PALLAVI AGARWAL PhD Cancer Research UK/ERC Research Associate
44 People in 2015
LINDA BASKCOMB MSc Cancer Research UK Senior Chief Research Laboratory Technician RIMMA BELOTSERKOVSKAYA PhD Cancer Research UK/A-T Society Research Associate
ANDREW BLACKFORD PhD Cancer Research UK Research Associate SERENA BOLOGNA PhD Cancer Research UK/ERC Research Associate TING-WEI (Will) CHIANG MSc Cambridge Overseas Trust PhD Student JULIA COATES MA Cancer Research UK Research Assistant
MATTHEW CORNWELL MChem Dept Chemistry/Cambridge Cancer Centre/School of Physical Sciences PhD Student
SATPAL JHUJH MSc ERC Research Technician
MUKERREM DEMIR BSc ERC Senior Research Technician/ Research Assistant
CARLOS LE SAGE PhD ERC Research Associate
GOPAL DHONDALAY PhD ERC Research Associate (Bioinformatics) KATE DRY PhD Cancer Research UK/ERC Information Specialist JOSEP FORMENT PhD A-T Society/Cancer Research UK Research Associate YARON GALANTY PhD ERC Senior Research Associate NICOLA GEISLER BSc Cancer Research UK/Wellcome Trust Chief Research Technician MAREIKE HERZOG BA Wellcome Trust PhD Student (joint with Sanger Institute)
DELPHINE LARRIEU PhD MRC Research Associate
DONNA LOWE BSc PHE PhD Student NATALIA LUKASHCHUK PhD Cancer Research UK Research Associate FRANCISCO MUNOZ MARTINEZ PhD Marie Curie Research Intra-European Fellow RYOTARO NISHI PhD Cancer Research UK Research Associate FABIO PUDDU PhD EU/ERC Research Associate HELEN REED PA/Secretary
ISRAEL SALGUERO CORBACHO PhD Cancer Research UK/Wellcome Trust Research Associate CHRISTINE SCHMIDT PhD ERC Research Associate MATYLDA SCZANIECKA-CLIFT PhD ERC Research Associate ALEXANDRA (SASHA) SELIVANOVA BBiotech Cancer Research UK/Wellcome Trust Senior Research Laboratory Technician (Maternity Cover) ROHAN SIVAPALAN BSc BBSRC/Horizon PhD Student SIYUE WANG MSc Wellcome Trust Senior Research Laboratory Technician DAVID WEISMANN PhD EMBO Research Fellow PAUL WIJNHOVEN BSc Cancer Research UK/ERC Research Assistant/PhD Student
TONY KOUZARIDES PhD FRS FMedSci Professor of Cancer Biology; Cancer Research UK Gibb Fellow; Member, European Molecular Biology Organization; ERC Advanced Researcher; (Member of the Department of Pathology) ANDREW BANNISTER PhD Cancer Research UK Senior Research Associate, Senior Radiation Protection Supervisor
ANDREJ ALENDAR MSc Cancer Research UK Research Assistant CARLOS ALMEIDA GUEDES DE MELO PhD ERC Research Associate PAULO AMARAL PhD ERC Research Associate
NAMSHIK HAN PhD ERC Research Associate (Bioinformatics)
ISAIA BARBIERI PhD Bloodwise Research Associate
SRI LESTARI MSc Cancer Research UK Senior Research Laboratory Technician
ESTER CANNIZZARO MSc Cancer Research UK PhD Student
NIKKI MANN BA PA/Secretary
KA HING CHE PhD Cancer Research UK/BBSRC Research Associate
VALENTINA MIGLIORI PhD EU Research Associate/King’s College Junior Research Fellow
ALISTAIR COOK GIBiol Cancer Research UK/ERC Chief Research Technician
GONZALO MILLAN ZAMBRANO PhD EMBO Research Fellow LUCA PANDOLFINI PhD ERC Research Associate
The Gurdon Institute
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SAM ROBSON PhD Cancer Research UK/ERC Research Associate (Bioinformatics)
HELENA SANTOS ROSA PhD Cancer Research UK Senior Research Associate
MEIKE WIESE MSc Cancer Research UK PhD Student
RICK LIVESEY MB BChir PhD Wellcome Trust Senior Investigator; University Reader in Molecular Neuroscience; (Member of the Department of Biochemistry) JAYNE FISHER PA/Secretary ALBERTO FRANGINI PhD Wellcome Trust Research Associate
PHILIPP BERG MRes Wellcome Trust PhD Student LAURA BRIGHTMAN BA PWS donation Research Assistant PHILIP BROWNJOHN PhD Alzheimer’s Research UK Research Associate TATYANA DIAS PhD Alzheimer’s Research UK Research Associate LEWIS EVANS PhD Wellcome Trust Senior Research Associate
TERESA KRIEGER MSci EPSRC PhD Student (Joint with Ben Simons) AYIBA MOMOH MSc Wellcome Trust Research Assistant/ PhD Student STEVEN MOORE PhD Wellcome Trust Research Associate TOMOKI OTANI MPhil Wellcome Trust Developmental Mechanisms PhD Student FRANCESCO PAONESSA PhD Alzheimer’s Research UK Research Associate MANUEL PETER PhD Innovative Medicines Initiative Research Associate
NATHALIE SAURAT BSc Alzheimer’s Research UK Research Assistant JAMES SMITH BSc Innovative Medicines Initiative Research Associate RAVI SOLANKI BA Sir Keith Peters/Coutts Trotter/ Cambridge Overseas Trust MB/PhD Student ALESSIO STRANO MPhil Wellcome Trust Developmental Mechanisms PhD Student VICTORIA STUBBS PhD Innovative Medicines Initiative Research Assistant ELLIE TUCK BSc Alzheimer’s Research UK Research Assistant
ERIC MISKA PhD Herchel Smith Professor of Molecular Genetics; Wellcome Trust Senior Investigator; Cancer Research UK Senior Research Fellow; Wellcome Trust Sanger Institute Affiliated Faculty Member; Member, European Molecular Biology Organization; ERC Independent Starting Researcher; (Member of the Department of Genetics) ALPER AKAY PhD Cancer Research UK Research Associate
TOMAS di DOMENICO PhD ERC/Cancer Research UK Research Associate (Bioinformatics)
FABIAN BRAUKMANN MA Herchel Smith PhD Student
MINGLIU DU PhD Wellcome Trust Research Associate
AHMET CAN BERKYUREK PhD HFSP Research Associate
LISE FREZAL PhD ERC/Herchel Smith Research Associate
ISABELA CUNHA NAVARRO MSc Science without Borders PhD Student
46 People in 2015
KATHARINA GAPP PhD Swiss National Science Foundation Fellow TANAY GHOSH PhD ERC/Cancer Research UK Research Associate SABRINA HUBER MA Cambridge PhD Training Programme in Chemical Biology and Molecular Medicine DAVID JORDAN PhD Herchel Smith Reseach Fellow JOANNA KOSALKA MPhil Wellcome Trust Developmental Mechanisms PhD Student MIRANDA LANDGRAF MA PA/Secretary
JÉREMIE LE PEN MPhil ERC PhD Student (formerly Wellcome Trust Developmental Biology PhD Student) MILAN MALINSKY MPhil Wellcome Trust Mathematical Biology PhD Student/Cancer Research UK Research Assistant EYAL MAORI PhD Herchel Smith Research Fellow WAYO MATSUSHIMA MD Nakajima Foundation/St John’s College Benefactors’ Scholar PhD Student RAGINI MEDHI BTech Commonwealth Scholar MPhil Student/Cancer Research UK Research Assistant
MARC RIDYARD PhD Cancer Research UK Lab Manager ALEXANDRA SAPETSCHNIG PhD ERC/ Wellcome Trust Senior Research Associate KIN MAN SUEN PhD Wellcome Trust Research Associate MÉLANIE TANGUY PhD Cancer Research UK Research Associate GRÉGOIRE VERNAZ MSc Wellcome Trust PhD Student EVA-MARIA WEICK PhD ERC Research Associate (formerly Herchel Smith PhD Student) OMER ZIV PhD Blavatnik Fellow/EMBO Postdoctoral Fellow
JONATHON PINES PhD FMedSci Director of Research in Cell Division; Cancer Research UK Senior Research Fellow; Member, European Molecular Biology Organization; (Member of the Department of Zoology) BARBARA DI FIORE PhD Cancer Research UK Research Associate MATTHEW GREETHAM PhD Cancer Research UK Research Associate ANJA HAGTING PhD Cancer Research UK Research Associate ANDREW HARRISON PhD MRC Research Associate
DAISUKE IZAWA PhD MRC Research Associate
BERNHARD STRAUSS PhD MRC Research Associate
MARK JACKMAN PhD Cancer Research UK Research Associate, Chemical Safety Officer
JILL TEMPLE MSc MRC Research Assistant
CHIARA MARCOZZI MSc Boehringer Ingelheim/BBSRC PhD Student OXANA NASHCHEKINA MSc Cancer Research UK Chief Research Technician
SAMUEL WIESER MSc MRC Research Associate (formerly Liechtenstein Government PhD Student) CLAUDIA WURZENBERGER PhD Marie Cure Research Intra-European Fellow KEIKO YATA PhD MRC Research Associate
AZIM SURANI PhD CBE FRS FMedSci Director of Germline and Epigenomics Research; Wellcome Trust Senior Investigator; Member, European Molecular Biology Organization; Member, Academia Europaea; Associate Fellow, Third World Academy of Sciences; (Member of the Department of Physiology, Development and Neuroscience) MAUD BORENSZTEIN PhD FRM Postdoctoral Fellow
DELPHINE COUGOT PhD Wellcome Trust Research Associate
DANG VINH DO PhD Wellcome Trust Research Associate
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LYNN FROGGETT PA/Secretary WOLFRAM GRUHN PhD EMBO Research Fellow UFUK GÃœNESDOGAN PhD Marie Curie Intra-European Fellow/ Leverhulme Early Career Research Fellow JAMIE HACKETT PhD HFSP Research Associate/Wellcome Trust Research Associate YUN HUANG BA MB-PhD Student
NAOKO IRIE PhD Wellcome Trust Research Associate/ BIRAX Research Associate
ANASTASIYA SYBIRNA MSc Wellcome Trust Stem Cell PhD Student
ELENA ITSKOVICH MSc Wellcome Trust PhD Student
THOR THEUNISSEN PhD Sir Henry Wellcome Postdoctoral Fellow (Based at Whitehead Institute, Boston, US)
SHINSEOG KIM PhD Wellcome Trust Research Associate TOSHIHIRO KOBAYASHI PhD Uehara Memorial Foundation Fellow CAROLINE LEE ONC Wellcome Trust Chief Research Technician, Radiation Protection Supervisor CHRISTOPHER PENFOLD PhD Wellcome Trust Research Associate (Bioinformatics) ROOPSHA SENGUPTA PhD Wellcome Trust Research Associate
WALFRED TANG MPhil Croucher Cambridge International PhD Student JULIA TISCHLER PhD APART Research Fellow/Wellcome Trust ISSF Interdisciplinary Senior Research Associate FREDERICK WONG PhD Wellcome Trust Research Associate JAN ZYLICZ MSc Wellcome Trust PhD Student
GROUP LEADERS JENNIFER GALLOP PhD Wellcome Trust Research Career Development Fellow; ERC Independent Starting Researcher; (Member of the Department of Biochemistry) ULRICH DOBRAMYSL PhD Wellcome Trust ISSF Junior Interdisciplinary Research Associate HELEN FOX MPhil Wellcome Trust Developmental Mechanisms PhD Student GUILHERME CORREIA MSc Wellcome Trust PhD Student FREDERIC DASTE PhD ERC Research Associate
48 People in 2015
LYNN FROGGETT PA/Secretary JONATHAN GADSBY PhD ERC Research Associate YOSHIKO INOUE PhD Wellcome Trust/ERC Research Associate
IRIS JARSCH PhD Wellcome Trust Research Associate JULIA MASON BSc ERC Research Assistant BENJAMIN RICHIER PhD ERC Research Associate DANIEL SAXTON BSc ERC Research Assistant HANAE SHIMO MSc Funai Foundation PhD Student VASJA URBANCIC PhD Wellcome Trust Research Associate
MERITXELL HUCH PhD Wellcome Trust Sir Henry Dale Fellow; Beit Prize Fellow; Affiliated Member of the Cambridge Stem Cell Institute; (Member of the Department of Physiology, Development and Neuroscience) LAURA BROUTIER PhD EMBO Research Fellow LUCIA CORDERO ESPINOZA MPhil Wellcome Trust Stem Cell PhD Student
LUIGI ALOIA PhD Wellcome Trust Research Associate
JOHN CRANG DPhil PA/Secretary DAISY HARRISON BA Wellcome Trust Research Assistant
CHRISTOPHER HINDLEY PhD SCI Seed Funding/Herchel Smith Research Associate GIANMARCO MASTROGIOVANNI MSc Marie Curie Initial Training Network PhD Student MIKEL McKIE MSci Wellcome Trust Research Assistant/ MRC PhD Student
EUGENIA PIDDINI PhD Royal Society Research Fellow; (Member of the Department of Zoology)
MICHAEL DINAN MPhil Wellcome Trust Developmental Mechanisms PhD Student MAJA GOSCHORSKA MPhil Cambridge Cancer Centre PhD Student
GOLNAR KOLAHGAR PhD Cancer Research UK Research Associate
YASMIN PATERSON MSci Cancer Research UK Research Assistant
KASIA KOZYRSKA MSc PhD Student
SASKIA SUIJKERBUIJK PhD Hubrecht Institute Research Fellow
IWO KUCINSKI MPhil Wellcome Trust Developmental Mechanisms PhD Student
SILVIA VIVARELLI PhD Cancer Research UK Research Associate
KATHY OSWALD MA PA/Secretary
LAURA WAGSTAFF PhD Cancer Research UK/Isaac Newton Trust Research Associate
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PHILIP ZEGERMAN PhD Worldwide Cancer Research International Research Fellow; (Member of the Department of Biochemistry)
GEYLANI CAN MSc Turkish Government PhD Student
CLARA COLLART PhD Collaborating Researcher from Professor Jim Smith’s lab, MRC NIMR, London
MARK JOHNSON PhD Worldwide Cancer Research Research Associate
VINCENT GAGGIOLI PhD Worldwide Cancer Research Research Associate
BARBARA SCHÖPF PhD Worldwide Cancer Research Research Associate
CHRISTINE HÄNNI MSc Cambridge Cancer Centre/Worldwide Cancer Research PhD Student
MARTIN HEMBERG PhD Associate Group Leader; Career Development Fellow and Group Leader, Wellcome Trust Sanger Institute TALLULAH ANDREWS PhD Postdoctoral Researcher
VLADIMIR KISILEV PhD Postdoctoral Researcher
ILIAS GEORGAKOPOULOSSOARES BSc PhD Student
MICHAEL KOSICKI PhD PhD Student
BEN SIMONS PhD Associate Group Leader; Herchel Smith Professor of Physics, Cavendish Laboratory EDOUARD HANNEZO PhD Postdoctoral Researcher CHRISTOPHER HINDLEY PhD SCI Seed Funding/Herchel Smith Research Associate (Joint with Meritxell Huch) JUERGEN FINK Wellcome Trust Stem Cell PhD Student (Joint with Bon-Kyoung Koo) PHILIP GREULICH PhD Postdoctoral Researcher
DAVID JORG PhD Postdoctoral Researcher TERESA KRIEGER BA MSci EPSRC PhD Student (Joint with Rick Livesey)
CRYSTAL McCLAIN PhD Postdoctoral Researcher (Joint with Robin Franklin) STEFFEN RULANDS PhD Postdoctoral Researcher JULIA TISCHLER PhD APART Research Fellow/Wellcome Trust ISSF Interdisciplinary Senior Research Associate (Joint with Azim Surani)
VISITING STUDENTS/RESEARCHERS BRIGID HOGAN PhD Sabbatical Visitor, Duke University School of Medicine, North Carolina, US PARSA AKBARI University of Cambridge, Part III Student
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EDWARD ALLGEYER PhD Visiting Researcher, University of Yale, US
ROBERT ARNES BSc Volunteer Researcher
ANDRÉ NICOLAU AQUIME GONÇALVES Visiting Student, CAPES Foundation, Ministry of Education Brazil,
AFNAN AZIZI MSc Wellcome Trust Developmental Biology Rotation Student
ROBERTA AZZARELLI PhD Collaborating Researcher, Hutchison MRC Research Centre
Trust, Cambridge UK
FABIO BALDIVIA POHL Visiting Undergraduate Student from University of São Paolo, Brazil
WEN FU Vacation Student, University of Wisconsin-Madison, Wisconsin, US
SIQIN BAO PhD Visiting Academic from College of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia VIVEK BHOGADI University of Cambridge, Vacation Student GINA BLAKE Wellcome Trust Developmental Biology PhD Rotation Student DANIEL BROOK University of Cambridge, Part III Student MAGDALENA BÜSCHER BSc Visiting Master’s Student, Ruprecht-Karls University of Heidelberg, Germany ORIOL CARITG CIRERA Visiting Student, School of Medicine, University of Barcelona, Spain ELISABETH CHEN PhD Rotation Student, Sanger Institute, Hinxton, Cambridge, UK ROSAMUND CLIFFORD University of Cambridge, Part II Student SAMANTHA COOPER BSDB/St John’s College Vacation Student ROBERT CRONSHAW University of Cambridge, Part II Student
HELENA FRANCIS University of Cambridge, Part III Student
ANA GASOL GARCIA Visiting Master’s Student, Vrije University, Amsterdam, Netherlands DAFNI GLINOS Visiting PhD Student, Sanger Institute, Hinxton, Cambridgeshire, UK OLIVIA HARRIS Wellcome Trust Rotation PhD Student (Stem Cell), University of Cambridge, UK EVA HIGGINBOTHAM BSc Wellcome Trust Developmental Biology Rotation PhD Student NICOLAS HIRCQ BSc Volunteer Researcher SILVIA HNATOVA University of Cambridge, Part II Student TOBIAS HOCHSTÖGER Visiting Student, Veterinary University of Vienna, Austria JOSHUA HODGSON University of Cambridge, Part II Student KATHARINA HÖLAND BSc Visiting Master’s Student, JuliusMaximilian University of Würzburg, Germany
CAIA DOMINICUS MSc Visiting Student, CIMR, Cambridge, UK
DOMINIK HUBER Visiting Student, University of Regensburg, Germany
JOSHUA DU PLOOY Vacation Student, University of Cambridge (King’s College), UK
MAXIMILIAN JAKOBS MSc Wellcome Trust Developmental Biology Rotation Student
KIRSTY FERGUSON University of Cambridge, Part III Student
ABIRAMI KATHIRAVELUPILLAI Work Experience Volunteer
MAGDALENA FIGLMUELLER Visiting Erasmus Student, IMC FH KREMS, Austria
CHRISTINE KLEINERT Visiting Erasmus Master’s Student, Potsdam University, Germany
BENJAMIN FISHER MA, MB, BChir Visiting Researcher, Cambridge University Hospitals NHS Foundation
ANNA KLUCNIKA University of Cambridge, Part II Student
EMMA KNEUSS BSc Visiting Erasmus Master’s Student, UPMC, Paris, France BART KRAMER BSc Visiting Master’s Erasmus Student, University of Utrecht, Netherlands IZABELA KUJAWIAK University of Cambridge, Part II Student DOMINIK MACAK BSc Visiting Erasmus Student, JuliusMaximilian University, Würzurg, Germany LINDSAY MALONE University of Cambridge, Vacation Student FABIAN MERKEL Visiting Erasmus Student, University of Bayreuth, Germany ALESSANDRA MERENDA MSc Marie Curie Initial Training Network PhD Student from Cambridge Stem Cell Institute, University of Cambridge, UK SOPHIA METZ Visiting Erasmus Student, University of Cologne, Germany ELLA MI University of Cambridge, Part II Student EMMA MI BSDB Vacation Student, University of Cambridge, UK TOM NEWMAN University of Cambridge, Part II Student MOHAMMED SAID NOOR University of Cambridge, Part II Student IOANA OLAN Wellcome Trust Rotation Student (Maths), University of Cambridge, UK GUILLERMO PARADA BSc Visiting Researcher, Catholic University of Chile, Santiago Chile CORINNE PHILLIPS University of Cambridge, BBSRC Rotation Student JESSICA PRINCE Visiting Medical Student, University of Oxford, UK
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SARA PRECIADO PhD Visiting Marie Curie Fellow, QMUL, London NAVIN BRIAN RAMAKRISHNA MBiochem A*STAR Developmental Biology Rotation Student CAROL READHEAD PhD Visiting Academic from University of Southern California, Los Angeles, US AMY REYNOLDS University of Cambridge, Part III Student ANDREW RUMBOL University of Cambridge, Part III Student ANDREW RUSSELL Vacation Student, University of Oxford, UK ANN-MARIE SHORROCKS University of Cambridge, Part III Student
SHRUTI SINGLA B.Tech-M.Tech Wellcome Trust Developmental Biology Rotation Student
MAVRIDOU VASILIKI Vacation Student, University of Thessaloniki, Greece
LIOR SODAY University of Cambridge, Part III Student
LOUISE VERON Visiting Master’s Student, ENS Cachan, France
ALINA STEIN Visiting Erasmus Student, Jacobs University, Bremen, Germany FERENC TAJTI BSc Visiting Erasmus Master’s Student, Maastrich University, The Netherlands GIULIA TANCA Visiting Erasmus Student, University of Sassari, Italy
TOM WEATHERBY Vacation Student (Fincham Bursary), University of Cambridge, UK EMMA WICTOME University of Cambridge, Part II Student KETI ZEKA PhD Visiting Researcher, University of L’Aquila, Italy
TERESA TOUDAL KNUDSEN University of Cambridge, Part II Student
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Group leader affiliations JULIE AHRINGER is a member of the Scientific Advisory Boards of the MRC Clinical Sciences Centre and Wormbase. ANDREA BRAND is a member of Council of The Royal Society, member of the Royal Society Diversity Committee, member of the Wellcome Trust/ Royal Society Sir Henry Dale Fellowship Committee and a Founding Board Member of The Rosalind Franklin Society (USA). She is on the Board of Directors of the Cambridge Science Centre and is a Patron of the Cambridge Science Festival. JOHN GURDON is a member of the Scientific Advisory Board of the Harvard Stem Cell Institute (USA) and on the PeerJ Academic Advisory Board. He is an Honorary Fellow of the Society of Biology and the American Association for Cancer Research, and an Honorary Member of the Biochemical Society. STEVE JACKSON is an Associate Faculty Member of the Wellcome Trust Sanger Institute and is Founding Scientist and Chief Scientific Officer (part-time) of MISSION Therapeutics Ltd. He is a member of the Scientific Advisory Boards for the MRC Protein Phosphorylation and Ubiquitylation Unit (Dundee), the Beatson Institute (Glasgow), the MRC Toxicology Unit (Leicester), the Radiation Oncology and Biology Institute (Oxford), the MRC Clinical Sciences Centre (London) and the Netherlands Cancer Institute (Amsterdam). He is on the Steering Committee for the Cambridge Cancer Centre, and is a member of the Cancer Research UK Science Committee and the Wellcome Trust Collaborative Awards Committee and a Consultant for Carrick Therapeutics UK Ltd. TONY KOUZARIDES is director
54 People in 2015
of the Milner Therapeutics Institute and Therapeutics Consortium at the University of Cambridge. He is also on the executive board of the Cambridge Cancer Centre. He is on the Scientific Advisory Board for the Centre for Genomic Research (Spain), Cabimer Biomedical Research Centre (Spain) and Centre for Epigenetics and Biology (Spain). He is a co-founder of Abcam Plc, Chroma Therapeutics and Iceni Therapeutics. He is founder and director of the Spanish cancer charity Vencer el Cancer (Conquer Cancer).
India Partnership Advisory Group, founder of CellCentric Ltd, a member of the Steering Committee for the UK Stem Cell Bank, and a member of the Royal Society Hooke Committee. He is also a member of the Scientific Advisory Board of the Institute of Stem Cell Biology and Regenerative Medicine, Bangalore, India.
RICK LIVESEY is Founder and Chief Scientific Officer of Talisman Therapeutics, a Principal Investigator of the Stem Cell Network of the MRC’s Dementias Platform UK, and Director of the Alzheimer’s Research UK Stem Cell Research Centre.
ANDREA BRAND – Neural Development; Fly
ERIC MISKA is an Associate Faculty Member of the Wellcome Trust Sanger Institute, a Member of the EMBO Fellowships Committee and co-founder of Iceni Therapeutics. BEN SIMONS is a Principal Investigator of the Wellcome Trust/ MRC Cambridge Stem Cell Institute. DANIEL ST JOHNSTON is Director of the Wellcome Trust 4-year PhD programme in Developmental Mechanisms at the University of Cambridge; a member of the Scientific Advisory Boards of the RIKEN Center for Developmental Biology, Kobe, Japan and the Institute of Developmental Biology in Marseille, France; a nonexecutive Director of the Company of Biologists; and co-founder and Advisory Board Chair of Disease Models and Mechanisms. AZIM SURANI is an affiliate member of the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute. He is also a member of the Cambridge-
Editorial boards of journals JULIE AHRINGER – eLife; PLoS Biology; PLoS Genetics; Molecular Systems Biology
JOHN GURDON – Current Biology; Development; Faculty of 1,000; Growth and Differentiation; International Journal of Developmental Biology; Proceedings of the National Academy of Sciences of the USA MERITXELL HUCH – Cogent Biology STEVE JACKSON – Aging; Biomolecules; Carcinogenesis; DNA Repair; EMBO Journal ; Genes and Development;The Scientist; Science Signaling (Board of Reviewing Editors) RICK LIVESEY – BMC Developmental Biology; Molecular Autism ERIC MISKA - PLOS Genetics, Journal of Cell Science, Environmental Epigenetics BEN SIMONS - Development DANIEL ST JOHNSTON – Development; Faculty of 1,000 AZIM SURANI – Cell; Nature Communications; Cell Stem Cell; BMC Epigenetics and Chromatin; Epigenome; Epigenomics; Epigenetic Regulators; Regenerative Medicine; Differentiation; Stem Cell Research and Therapy; Faculty of 1,000; Cell Research; Cell Discovery
Publications in 2015 Akay A, Sarkies P, Miska EA (2015) E. coli OxyS noncoding RNA does not trigger RNAi in C. elegans. Sci Rep 5: doi: 10.1038/srep09597. Ashe A, Sarkies P, Le Pen J, Tanguy M, Miska EA (2015) Antiviral RNA Interference against Orsay Virus Is neither Systemic nor Transgenerational in Caenorhabditis elegans. J Virol 89: 12035–12046. Balmus G, Lim PX, Oswald A, Hume KR, Cassano A, Pierre J, Hill A, Huang W, August A, Stokol T, Southard T, Weiss RS (2015) HUS1 regulates in vivo responses to genotoxic chemotherapies. Oncogene print volume: 35(5): 662–669. (Jackson group) Balmus G, Karp NA, Ng BL, Jackson SP, Adams DJ, McIntyre RE (2015) A high-throughput in vivo micronucleus assay for genome instability screening in mice. Nat Protoc 10: 205–215. Barbera M, Pietro MD, Walker E, Brierley C, MacRae S, Simons BD, Jones PH, Stingl J, Fitzgerald RC (2015) The human squamous oesophagus has widespread capacity for clonal expansion from cells at diverse stages of differentiation. Gut 64: 11–19. Beli P, Jackson SP (2015) Ubiquitin regulates dissociation of DNA repair factors from chromatin. Oncotarget 6: 14727–14728. Bergstralh DT, Lovegrove HE, St Johnston D (2015) Lateral adhesion drives reintegration of misplaced cells into epithelial monolayers. Nat Cell Biol 17: 1497–1503. Blackford AN, Nieminuszczy J, Schwab RA, Galanty Y, Jackson SP, Niedzwiedz W (2015) TopBP1 interacts with BLM to maintain genome stability but is dispensable for preventing BLM degradation. Mol Cell 57: 1133– 1141. Blake JA et al. (2015) Gene ontology consortium: Going forward. Nucleic Acids Research 43: D1049–D1056. (Brown group) Boije H, Rulands S, Dudczig S, Simons BD, Harris WA (2015) The Independent Probabilistic Firing of
Transcription Factors: A Paradigm for Clonal Variability in the Zebrafish Retina. Dev Cell 34: 532–543. Brennand KJ, Marchetto MC, Benvenisty N, Brüstle O, Ebert A, Izpisua Belmonte JC, Kaykas A, Lancaster MA, Livesey FJ, McConnell MJ, McKay RD, Morrow EM, Muotri AR, Panchision DM, Rubin LL, Sawa A, Soldner F, Song H, Studer L, Temple S, Vaccarino FM, Wu J, Vanderhaeghen P, Gage FH, Jaenisch R (2015) Creating Patient-Specific Neural Cells for the In Vitro Study of Brain Disorders. Stem Cell Reports 5: 933–945. Broderick R, Nieminuszczy J, Blackford AN, Winczura A, Niedzwiedz W (2015) TOPBP1 recruits TOP2A to ultrafine anaphase bridges to aid in their resolution. Nature Communications 6: 6572. (Jackson group) Brown JS, Jackson SP (2015) Ubiquitylation, neddylation and the DNA damage response. Open Biol 5: doi: 10.1098/rsob.150018. Brown JS, Lukashchuk N, Sczaniecka-Clift M, Britton S, le Sage C, Calsou P, Beli P, Galanty Y, Jackson SP (2015) Neddylation promotes ubiquitylation and release of Ku from DNA-damage sites. Cell Rep 11: 704–714. Bulgakova NA, Brown NH (2015) Drosophila p120catenin is critical for endocytosis of the dynamic E-cadherin-Bazooka complex. J Cell Sci print volume: 129(3): 477–482 Cattenoz PB, Popkova A, Southall T, Aiello G, Brand A, Giangrande A (2015) Functional Conservation of the Glide/Gcm Regulatory Network Controlling Glia, Hemocyte and Tendon Cell Differentiation in Drosophila. Genetics print volume: 202(1): 191–219. Coelho PA, Bury L, Shahbazi MN, Liakath-Ali K, Tate PH, Wormald S, Hindley CJ, Huch M, Archer J, Skarnes WC, Zernicka-Goetz M, Glover DM (2015) Over-expression of Plk4 induces centrosome amplification, loss of primary cilia and associated tissue hyperplasia in the mouse. Open Biol 5(12) doi: 10.1098/rsob.150209. Crosby MA et al. (2015) Gene model annotations for Drosophila melanogaster: The rule-benders. G3: Genes, Genomes, Genetics 5: 1737–1749. (Brown group)
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Davies OR, Forment JV, Sun M, Belotserkovskaya R, Coates J, Galanty Y, Demir M, Morton CR, Rzechorzek NJ, Jackson SP, Pellegrini L (2015) CtIP tetramer assembly is required for DNA-end resection and repair. Nat Struct Mol Biol 22: 150–157. Di Fiore B, Davey NE, Hagting A, Izawa D, Mansfeld J, Gibson TJ, Pines J (2015) The ABBA motif binds APC/C activators and is shared by APC/C substrates and regulators. Dev Cell 32: 358–372. Füllgrabe A, Joost S, Are A, Jacob T, Sivan U, Haegebarth A, Linnarsson S, Simons BD, Clevers H, Toftgård R, Kasper M (2015) Dynamics of Lgr6(+) Progenitor Cells in the Hair Follicle, Sebaceous Gland, and Interfollicular Epidermis. Stem Cell Reports doi: 10.1016/j. stemcr.2015.09.013. Fong CY, Gilan O, Lam EY, Rubin AF, Ftouni S, Tyler D, Stanley K, Sinha D, Yeh P, Morison J, Giotopoulos G, Lugo D, Jeffrey P, Lee SC, Carpenter C, Gregory R, Ramsay RG, Lane SW, Abdel-Wahab O, Kouzarides T, Johnstone RW, Dawson SJ, Huntly BJ, Prinjha RK, Papenfuss AT, Dawson MA (2015) BET inhibitor resistance emerges from leukaemia stem cells. Nature 525: 538–542. Forment JV, Jackson SP (2015) A flow cytometry-based method to simplify the analysis and quantification of protein association to chromatin in mammalian cells. Nat Protoc 10: 1297–1307. Forment JV, Jackson SP, Pellegrini L (2015) When two is not enough: a CtIP tetramer is required for DNA repair by Homologous Recombination. Nucleus 6: 344–348. Gill SJ, Travers J, Pshenichnaya I, Kogera FA, Barthorpe S, Mironenko T, Richardson L, Benes CH, Stratton MR, McDermott U, Jackson SP, Garnett MJ (2015) Combinations of PARP Inhibitors with Temozolomide Drive PARP1 Trapping and Apoptosis in Ewing’s Sarcoma. PLoS One doi: 10.1371/journal. pone.0140988.
Harley ME, Murina O, Leitch A, Higgs MR, Bicknell LS, Yigit G, Blackford AN, Zlatanou A, Mackenzie KJ, Reddy K, Halachev M, McGlasson S, Reijns MA, Fluteau A, Martin CA, Sabbioneda S, Elcioglu NH, Altmüller J, Thiele H, Greenhalgh L, Chessa L, Maghnie M, Salim M, Bober MB, Nürnberg P, Jackson SP, Hurles ME, Wollnik B, Stewart GS, Jackson AP (2015) TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism. Nat Genet 48: 36–43. Herberg S, Simeone A, Oikawa M, Jullien J, Bradshaw CR, Teperek M, Gurdon J, Miyamoto K (2015) Histone H3 lysine 9 trimethylation is required for suppressing the expression of an embryonically activated retrotransposon in Xenopus laevis. Sci Rep doi: 10.1038/srep14236. Higgs MR, Reynolds JJ, Winczura A, Blackford AN, Borel V, Miller ES, Zlatanou A, Nieminuszczy J, Ryan EL, Davies NJ, Stankovic T, Boulton SJ, Niedzwiedz W, Stewart GS (2015) BOD1L is required to suppress deleterious resection of stressed replication forks. Molecular Cell 59: 462–477. (Jackson group) Hiramuki Y, Sato T, Furuta Y, Surani MA, Sehara-Fujisawa A (2015) Mest but Not MiR-335 Affects Skeletal Muscle Growth and Regeneration. PLoS One 10: e0130436– e0130436. Huber SM, van Delft P, Mendil L, Bachman M, Smollett K, Werner F, Miska EA, Balasubramanian S (2015) Formation and abundance of 5-hydroxymethylcytosine in RNA. Chembiochem 16: 752–755. Huch M (2015) Regenerative biology: The versatile and plastic liver. Nature 517: 155–156. Huch M (2015) Building stomach in a dish. Nat Cell Biol 17: 966–967.
Giraddi RR, Shehata M, Gallardo M, Blasco MA, Simons BD, Stingl J (2015) Stem and progenitor cell division kinetics during postnatal mouse mammary gland development. Nat Commun doi: 10.1038/ncomms9487.
Huch M, Gehart H, van Boxtel R, Hamer K, Blokzijl F, Verstegen MM, Ellis E, van Wenum M, Fuchs SA, de Ligt J, van de Wetering M, Sasaki N, Boers SJ, Kemperman H, de Jonge J, Ijzermans JN, Nieuwenhuis EE, Hoekstra R, Strom S, Vries RR, van der Laan LJ, Cuppen E, Clevers H (2015) Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 160: 299–312.
Gurdon J (2015) Harveian Oration 2014: Stem cells and cell replacement prospects. Clin Med (Lond) 15: 160–167.
Huch M, Koo BK (2015) Modeling mouse and human development using organoid cultures. Development 142: 3113–3125.
56 Publications in 2015
Irie N, Weinberger L, Tang WW, Kobayashi T, Viukov S, Manor YS, Dietmann S, Hanna JH, Surani MA (2015) SOX17 Is a Critical Specifier of Human Primordial Germ Cell Fate. Cell 160 (1–2): 253–268. Kang J, Lienhard M, Pastor WA, Chawla A, Novotny M, Tsagaratou A, Lasken RS, Thompson EC, Surani MA, Koralov SB, Kalantry S, Chavez L, Rao A (2015) Simultaneous deletion of the methylcytosine oxidases Tet1 and Tet3 increases transcriptome variability in early embryogenesis. Proc Natl Acad Sci USA 112: E4236– E4245. Khuc Trong P, Doerflinger H, Dunkel J, St Johnston D, Goldstein RE (2015) Cortical microtubule nucleation can organise the cytoskeleton of Drosophila oocytes to define the anteroposterior axis. Elife doi: 10.7554/ eLife.06088. Kirwan P, Turner-Bridger B, Peter M, Momoh A, Arambepola D, Robinson HP, Livesey FJ (2015) Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro. Development 142: 3178–3187. Klapholz B, Herbert SL, Wellmann J, Johnson R, Parsons M, Brown NH (2015) Alternative mechanisms for talin to mediate integrin function. Curr Biol 25: 847–857. Knock E, Pereira J, Lombard PD, Dimond A, Leaford D, Livesey FJ, Hendrich B (2015) The methyl binding domain 3/nucleosome remodelling and deacetylase complex regulates neural cell fate determination and terminal differentiation in the cerebral cortex. Neural Dev doi: 10.1186/s13064-015-0040-z. Kolahgar G, Suijkerbuijk SJ, Kucinski I, Poirier EZ, Mansour S, Simons BD, Piddini E (2015) Cell Competition Modifies Adult Stem Cell and Tissue Population Dynamics in a JAK-STAT-Dependent Manner. Dev Cell 34: 297–309. Koziol MJ, Bradshaw CR, Allen GE, Costa AS, Frezza C, Gurdon JB (2015) Identification of methylated deoxyadenosines in vertebrates reveals diversity in DNA modifications. Nat Struct Mol Biol 23: 24–30. Krieger T, Simons BD (2015) Dynamic stem cell heterogeneity. Development 142: 1396–1406. Latorre I, Chesney MA, Garrigues JM, Stempor P, Appert A, Francesconi M, Strome S, Ahringer J (2015) The
DREAM complex promotes gene body H2A.Z for target repression. Genes Dev 29: 495–500. Lavagnolli T, Gupta P, Hörmanseder E, Mira-Bontenbal H, Dharmalingam G, Carroll T, Gurdon JB, Fisher AG, Merkenschlager M (2015) Initiation and maintenance of pluripotency gene expression in the absence of cohesin. Genes Dev 29: 23–38. Livesey FJ (2015) Reconstructing the neuronal milieu intérieur. Proc Natl Acad Sci USA 112: 6250–6251. Maartens AP, Brown NH (2015) The many faces of cell adhesion during Drosophila muscle development. Dev Biol 401: 62–74. Maartens AP, Brown NH (2015) Anchors and signals: the diverse roles of integrins in development. Curr Top Dev Biol 112: 233–272. Macaulay IC, Haerty W, Kumar P, Li YI, Hu TX, Teng MJ, Goolam M, Saurat N, Coupland P, Shirley LM, Smith M, Van der Aa N, Banerjee R, Ellis PD, Quail MA, Swerdlow HP, Zernicka-Goetz M, Livesey FJ, Ponting CP, Voet T (2015) G&T-seq: parallel sequencing of single-cell genomes and transcriptomes. Nat Methods 12: 519–522. Malinsky M, Challis RJ, Tyers AM, Schiffels S, Terai Y, Ngatunga BP, Miska EA, Durbin R, Genner MJ, Turner GF (2015) Genomic islands of speciation separate cichlid ecomorphs in an East African crater lake. Science 350: 1493–1498. Marshall OJ, Brand AH (2015) damidseq_pipeline: an automated pipeline for processing DamID sequencing datasets. Bioinformatics 31: 3371–3373. Matthews BB et al. (2015) Gene model annotations for Drosophila melanogaster: Impact of high-throughput data G3: Genes, Genomes, Genetics 5: 1721–1736. (Brown group) McConnell MJ, Durand L, Langley E, Coste-Sarguet L, Zelent A, Chomienne C, Kouzarides T, Licht JD, Guidez F (2015) Post transcriptional control of the epigenetic stem cell regulator PLZF by sirtuin and HDAC deacetylases. Epigenetics Chromatin doi: 10.1186/ s13072-015-0030-8 Medvinsky A, Livesey FJ (2015) On human development: lessons from stem cell systems. Development 142: 17–20.
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Meir M, Galanty Y, Kashani L, Blank M, Khosravi R, Fernández-Ávila MJ, Cruz-Garcia A, Star A, Shochot L, Thomas Y, Garrett LJ, Chamovitz DA, Bodine DM, Kurz T, Huertas P, Ziv Y, Shiloh Y (2015) The COP9 signalosome is vital for timely repair of DNA doublestrand breaks. Nucleic Acids Res 43: 4517–4530. (Jackson group) Miska E (2015) Transgenerational epigenetic inheritance and RNAe FEBS Journal 282: 36–36. Miyamoto K, Simpson D, Gurdon JB (2015) Manipulation and in vitro maturation of Xenopus laevis oocytes, followed by intracytoplasmic sperm injection, to study embryonic development. J Vis Exp doi: 10.3791/52496. Miyamoto K, Suzuki KT, Suzuki M, Sakane Y, Sakuma T, Herberg S, Simeone A, Simpson D, Jullien J, Yamamoto T, Gurdon JB (2015) The Expression of TALEN before Fertilization Provides a Rapid Knock-Out Phenotype in Xenopus laevis Founder Embryos. PLoS One doi: 10.1371/journal.pone.0142946. Moore S, Evans LD, Andersson T, Portelius E, Smith J, Dias TB, Saurat N, McGlade A, Kirwan P, Blennow K, Hardy J, Zetterberg H, Livesey FJ (2015) APP metabolism regulates tau proteostasis in human cerebral cortex neurons. Cell Rep 11: 689–696. Moore SJ, Saurat NG, Livesey FJ (2015) Cortical Differentiation of Human Pluripotent Cells for in vitro Modeling of Alzheimer’s Disease. Methods Mol Biol doi: 10.1007/978-1-4939-2627-5_16. Nantasanti S, Spee B, Kruitwagen HS, Chen C, Geijsen N, Oosterhoff LA, van Wolferen ME, Pelaez N, Fieten H, Wubbolts RW, Grinwis GC, Chan J, Huch M, Vries RR, Clevers H, de Bruin A, Rothuizen J, Penning LC, Schotanus BA (2015) Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids. Stem Cell Reports 5: 895–907. Ochi T, Blackford AN, Coates J, Jhujh S, Mehmood S, Tamura N, Travers J, Wu Q, Draviam VM, Robinson CV, Blundell TL, Jackson SP (2015) PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair. Science 347: 185–188. Picaud S, Fedorov O, Thanasopoulou A, Leonards K, Jones K, Meier J, Olzscha H, Monteiro O, Martin S, Philpott M, Tumber A, Filippakopoulos P, Yapp C, Wells C, Che KH,
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Bannister A, Robson S, Kumar U, Parr N, Lee K, Lugo D, Jeffrey P, Taylor S, Vecellio ML, Bountra C, Brennan PE, O’Mahony A, Velichko S, Müller S, Hay D, Daniels DL, Urh M, La Thangue NB, Kouzarides T, Prinjha R, Schwaller J, Knapp S (2015) Generation of a Selective Small Molecule Inhibitor of the CBP/p300 Bromodomain for Leukemia Therapy. Cancer Res 75: 5106–5119. Puddu F, Oelschlaegel T, Guerini I, Geisler NJ, Niu H, Herzog M, Salguero I, Ochoa-Montaño B, Viré E, Sung P, Adams DJ, Keane TM, Jackson SP (2015) Synthetic viability genomic screening defines Sae2 function in DNA repair. EMBO J 34: 1509–1522. Rawlins EL (2015) Stem cells: Emergency back-up for lung repair. Nature 517: 556–557. Reik W, Surani MA (2015) Germline and Pluripotent Stem Cells. Cold Spring Harb Perspect Biol doi:10.1101/ cshperspect.a019422. Roshan A, Murai K, Fowler J, Simons BD, NikolaidouNeokosmidou V, Jones PH (2015) Human keratinocytes have two interconvertible modes of proliferation. Nat Cell Biol doi:10.1038/ncb3282. Sapetschnig A, Sarkies P, Lehrbach NJ, Miska EA (2015) Tertiary siRNAs mediate paramutation in C. elegans. PLoS Genet doi:10.1371/journal.pgen.1005078. Sarkies P, Selkirk ME, Jones JT, Blok V, Boothby T, Goldstein B, Hanelt B, Ardila-Garcia A, Fast NM, Schiffer PM, Kraus C, Taylor MJ, Koutsovoulos G, Blaxter ML, Miska EA (2015) Ancient and novel small RNA pathways compensate for the loss of piRNAs in multiple independent nematode lineages. PLoS Biol doi: 10.1371/journal.pbio.1002061. Schmidt CK, Galanty Y, Sczaniecka-Clift M, Coates J, Jhujh S, Demir M, Cornwell M, Beli P, Jackson SP (2015) Systematic E2 screening reveals a UBE2DRNF138-CtIP axis promoting DNA repair. Nat Cell Biol 17: 1458–1470. Silva AP, Ryan DP, Galanty Y, Low JK, Vandevenne M, Jackson SP, Mackay JP (2015) The N-terminal Region of Chromodomain Helicase DNA-binding Protein 4 (CHD4) Is Essential for Activity and Contains a High Mobility Group (HMG) Box-like-domain That Can Bind Poly(ADP-ribose). J Biol Chem 291: 924–938.
Simons BD (2015) Deep sequencing as a probe of normal stem cell fate and preneoplasia in human epidermis. Proc Natl Acad Sci USA print volume: 113(1): 128–133. Sposito T, Preza E, Mahoney CJ, Setó-Salvia N, Ryan NS, Morris HR, Arber C, Devine MJ, Houlden H, Warner TT, Bushell TJ, Zagnoni M, Kunath T, Livesey FJ, Fox NC, Rossor MN, Hardy J, Wray S (2015) Developmental regulation of tau splicing is disrupted in stem cell-derived neurons from frontotemporal dementia patients with the 10 + 16 splice-site mutation in MAPT. Hum Mol Genet 24: 5260–5269. St Johnston D (2015) The renaissance of developmental biology. PLoS Biol doi: 10.1371/journal.pbio.1002149. Surani MA (2015) Human Germline: A New Research Frontier. Stem Cell Reports 4: 955–960. Tang WW, Dietmann S, Irie N, Leitch HG, Floros VI, Bradshaw CR, Hackett JA, Chinnery PF, Surani MA (2015) A Unique Gene Regulatory Network Resets the Human Germline Epigenome for Development. Cell 161: 1453–1467. Theodoulou NH, Bamborough P, Bannister AJ, Becher I, Bit RA, Che KH, Chung CW, Dittmann A, Drewes G, Drewry DH, Gordon L, Grandi P, Leveridge M, Lindon M, Michon AM, Molnar J, Robson SC, Tomkinson NC, Kouzarides T, Prinjha RK, Humphreys PG (2015) Discovery of I-BRD9, a Selective Cell Active Chemical Probe for Bromodomain Containing Protein 9 Inhibition. J Med Chem doi: 10.1021/acs.jmedchem.5b00256. Walrant A, Saxton DS, Correia GP, Gallop JL (2015) Triggering actin polymerization in Xenopus egg extracts from phosphoinositide-containing lipid bilayers. Methods Cell Biol 128: 125–147.
Willem M, Tahirovic S, Busche MA, Ovsepian SV, Chafai M, Kootar S, Hornburg D, Evans LD, Moore S, Daria A, Hampel H, Müller V, Giudici C, Nuscher B, WenningerWeinzierl A, Kremmer E, Heneka MT, Thal DR, Giedraitis V, Lannfelt L, Müller U, Livesey FJ, Meissner F, Herms J, Konnerth A, Marie H, Haass C (2015) η·-Secretase processing of APP inhibits neuronal activity in the hippocampus. Nature 526: 443–447. Yang S, Butov LV, Simons BD, Campman KL, Gossard AC (2015) Fluctuation and commensurability effect of exciton density wave Phys Rev B 91, 245302. Yuan Y, Britton S, Delteil C, Coates J, Jackson SP, Barboule N, Frit P, Calsou P (2015) Single-stranded DNA oligomers stimulate error-prone alternative repair of DNA double-strand breaks through hijacking Ku protein. Nucleic Acids Res 43: 10264–10276. Zegerman P (2015) Evolutionary conservation of the CDK targets in eukaryotic DNA replication initiation. Chromosoma 124: 309–321. Zegerman P (2015) Cell scientist to watch: Philip Zegerman. J Cell Sci 128: 3361–3362. Zimmer J, Tacconi EM, Folio C, Badie S, Porru M, Klare K, Tumiati M, Markkanen E, Halder S, Ryan A, Jackson SP, Ramadan K, Kuznetsov SG, Biroccio A, Sale JE, Tarsounas M (2015) Targeting BRCA1 and BRCA2 Deficiencies with G-Quadruplex-Interacting Compounds. Mol Cell 4;61(3):449-60. Zylicz JJ, Dietmann S, Günesdogan U, Hackett JA, Cougot D, Lee C, Surani MA (2015) Chromatin dynamics and the role of G9a in gene regulation and enhancer silencing during early mouse development. Elife doi:10.7554/eLife.09571.
Watson JK, Rulands S, Wilkinson AC, Wuidart A, Ousset M, Van Keymeulen A, Göttgens B, Blanpain C, Simons BD, Rawlins EL (2015) Clonal Dynamics Reveal Two Distinct Populations of Basal Cells in Slow-Turnover Airway Epithelium. Cell Rep 12: 90–101. Wieser S, Pines J (2015) The biochemistry of mitosis. Cold Spring Harb Perspect Biol doi: 10.1101/ cshperspect.a015776. Wijnhoven P, Konietzny R, Blackford AN, Travers J, Kessler BM, Nishi R, Jackson SP (2015) USP4 AutoDeubiquitylation Promotes Homologous Recombination. Mol Cell 60: 362–373.
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Awards and prizes June: Steve Jackson delivered the Academy of Medical Sciences 2015 Raymond and Beverly Sackler Distinguished Lecture on 11th June at the University of Leeds, and on 25th June at the School of Clinical Medicine, University of Cambridge, on ‘Cellular responses to DNA damage: mechanistic insights and new cancer therapies’.
July: Ben Simons was awarded the Gabor Medal from the Royal Society in recognition of his interdisciplinary work combining the life sciences and physics, “analysing stem cell lineages in development, tissue homeostasis and cancer, revolutionising our understanding of stem cell behaviour in vivo”.
2015 March: Eric Miska received a Program Grant from the International Human Frontier Science Program Organization, designed to support novel collaborations among international teams of scientists. The other team members are Thomas Duchaine of the Goodman Cancer Research Centre, Montreal, Canada, and Mihail Sarov of the Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany. They are researching functional genomics of small RNAmediated epimutations in C. elegans. 60 Activities and impacts in 2015
Nicola Lawrence from the Gurdon Institute’s Imaging Facility and Nele Dieckmann of the Cambridge Institute for Medical Research were recipients of a Wellcome Trust Image Award. Their winning super-resolution micrograph was created using 3D structured illumination microscopy and shows a natural killer cell (left) examining a less bright, slightly rounder cell (right) for signs of disease. Part of the immune system, the natural killer cell is armed with toxic chemicals (red). The cells are each ~20 μm in diameter.
December: ‘Supernova’, an image captured by Philipp Berg in Rick Livesey’s group, won the 2015 Picturing Parkinson’s competition. The image shows a mass of human stem cells that have been induced to form neurons in culture. Another of his images, entitled ‘Neurons blooming in culture’, also made the top 10 selection. The University of Cambridge film showing how scientists use mice and alternative models to study cancer, featuring Meritxell Huch (see p. 66), received the 2015 Openness Award in the category of ‘Website or Use of New Media’, given by Understanding Animal Research. Azim Surani’s attention-grabbing paper on creating human germ cells in vitro from stem cells (Irie N et al., p. 57) was chosen for ‘Best of Cell 2015’.
November: Steve Jackson was awarded the Gagna A. and Ch. Van Heck Prize 2015 “for his cardinal contributions related to cellular events that detect, signal the presence of, and repair DNA damage”. The triennial prize of €75,000 is awarded by the Fonds de la Recherche Scientifique-FNRS, based in Brussels, where Steve gave a presentation at the award ceremony.
Meike Wiese, PhD Student in Tony Kouzarides’ group, won the poster prize (and €100) at the European Association for Cancer Research conference on Basic Epigenetic Mechanisms in Cancer, in Berlin. The Gurdon Institute
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Global reach in 2015 Simons Foundation National Centre for Biological Sciences
CSHL Banbury Center
Genentech Salk Institute for Biological Sciences
Postdoc Harvard Medical School
MD Anderson Cancer Center University of Miami Senior Scientist Abbvie Many of our 2015 leavers went to high-profile scientific positions, including as group leaders, around the world. Our own group leaders gave more than 190 external talks and presentations in 2015. A small selection of the host institutions is highlighted here.
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Postdoc Memorial Sloan Kettering Cancer Center
Bar-Ilan University
University of Chile
Director of R&D Koniku Ltd
Roslin Institute Group Leader University of Leeds
Senior Scientist Horizon Discovery Danish Stem Cell Center
Lecturer University of Sheffield
Postdoc Hubrecht Institute
Senior Scientist Immunocore Ltd
Postdoc German Cancer Research Center
University College London Institut Pasteur Group Leader Institut Pasteur
Vienna Biocenter
Postdoc Institut Curie
Patent Attorney Trainee Munich
Postdoc University of Tokyo
Head of Division Institute of Cancer Research
Assistant Professor Ritsumeikan University Group Leader Kinki University Chinese University of Hong Kong
Academia Sinica Capital University of Medical Sciences The Gurdon Institute
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Engaging the public Our public engagement programme aims to foster exchange between our scientists and the public, provide an insight into our particular research topics, and inspire the next generation of scientists. Volunteers are drawn from across the Institute to staff the events, which are organised by the Institute’s Public Engagement Officer, Hélène Doerflinger.
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schoolchildren visited by our Mobile Lab
A team of five scientists arrive at a local state primary school with a van full of microscopes and specimens and run a twohour, hands-on workshop for 30 children at a time. The Year 5 children put on their lab coats and are guided to use the microscopes for mini experiments, to discover what a cell looks like, or to understand the life of a model organism such as the fruit fly.
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University Technical College students attend workshop series
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sixth-form students consider science careers
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University of Cambridge alumni tour the Institute
As part of the University’s 25th Alumni Festival, we hosted adult visitors to a talk about neural stem cell biology and Alzheimer’s disease and a guided tour of three different labs.
Year 12 students with an interest in applying to the University of Cambridge from schools all over the country can visit the city for a day as part of the Cambridge Colleges’ Physics Experience. We provided a seminar on cell division and cancer, a microscopy session observing normal and cancerous tissues, a demonstration of our super-resolution microscope, and a discussion with some of our scientists about their research and career paths. Several of these students returned to take part in our work experience programme.
Cambridge’s new UTC asked the Institute to collaborate on an eight-week workshop for Year 12 students about confocal microscopy, using Drosophila as a model. As well as hosting a visit at the Institute to demonstrate our different microscopes, our researchers gave two seminars and provided flies and technical advice.
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people ‘Seeing closer’ through our microscopes at the Royal Society
A stand for
30,000 visitors at European Researchers’ Night
Six Bachelor’s students from Tokyo Institute of Technology visited the Institute as part of their International Research Opportunities Program (TiROP).
This special event marked the 350th anniversary of Robert Hooke’s Micrographia, run in conjunction with the Big Draw charity. The Institute was invited to run a ‘look and draw’ activity with 20 microscopes. Our specimens for observation included fleas, ants, feathers, seeds and others that Robert Hooke also examined.
At the request of the Wellcome Trust we took our travelling microscopes to London to be part of the annual celebration, European Researchers’ Night, at the Natural History Museum. In total, 200 activities were on offer to a largely adult audience at this evening event. Our researchers discussed how cells organise themselves within a tissue and what happens when this process goes wrong, and gave the public an opportunity to observe many cell types under the microscope.
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undergraduate visitors from the Tokyo Institute of Technology
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visitors through our doors for our Science Festival event We opened our doors as part of the free Cambridge Science Festival, offering members of the public a room full of handson activities about developmental biology and cancer biology and a lecture by John Gurdon. The activities were designed to be accessible to all, including: watch the first division of a frog egg, see your own cheek cells, examine fluorescent worms, discover the lifestyle of the fly and meet our scientists.
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school students experienced working in a lab
Our programme is a unique opportunity for sixth-form students to spend a week in a lab, to discover more about the research process, the techniques we use and what working in the lab is really like.
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Events and media highlights January: Continuing news coverage (Sunday Times: “Cell breakthrough to bring two-dad babies”, Daily Mail and Cambridge News online) of Azim Surani’s paper on creating human germ cells in vitro from stem cells (Irie N et al., p. 57).
May: Azim Surani’s work on epigenetic resetting and how some epigenetic marks may be passed to the next generation is covered in The Telegraph online and New Scientist online (“First evidence of how parents’ lives could change children’s DNA”).
Cambridge News cover the opening of the Alzheimer’s Research UK Stem Cell Research Centre, run by Rick Livesey within the Gurdon Institute, and funded with a donation from the Alborada Trust.
2015 February: Rick Livesey interviewed on BBC R4 Inside Science about modelling brain diseases in the lab using neurons grown from patients’ skin cells.
April: Meritxell Huch appears in the University of Cambridge film ‘Fighting Cancer: Animal Research at Cambridge’, covered in Wired (“Inside the animal lab where cancer cures are tested”). The video looks at how mice are helping cancer research and the facilities in which they are housed, exploring issues of animal welfare and the search for replacements. By the end of 2015 the film had been viewed more than 13,000 times. The Times and others cover the news that breast cancer drug olaparib, developed from Steve Jackson’s research, shows promise in treating prostate cancer.
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July: Tony Kouzarides announced the formation of the Therapeutics Consortium and the Milner Therapeutics Institute that will house research partnerships on the Cambridge Biomedical Campus (Drug Discovery & Development “Innovative New Consortium Formed to Develop, Study Early Stage Drugs”).
October: Daniel Zeichner visited the ARUK Stem Cell Research Centre to hear about Rick Livesey’s research and discuss the importance of staying in the EU to continued science funding and recruiting the best researchers. Zeichner noted his visit in a parliamentary debate on the UK Science Budget in the House of Commons on 21 October (Hansard Vol. 600, No. 54) (Cambridge News “MP Daniel Zeichner praises Alzheimer’s Research UK’s Stem Cell Research Centre in Cambridge”).
December: NICE approves use of olaparib by the NHS in England (Daily Mail online “NHS chiefs’ U-turn over life-extending ovarian cancer drug: Officials finally relent and allow women access to treatment that can increase lives by several months”). Azim Surani writes in The Conversation (How close are we to successfully editing genes in human embryos?) after attending the International Summit on Human Gene Editing in Washington, DC and the Progress Educational Trust annual conference (Buzz Feed “Let scientists experiment on older embryos, says stem cell pioneer”).
Steve Jackson’s work chosen for a poster in the University’s £2 billion fundraising campaign, ‘Yours Cambridge’.
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Seminars and celebrations Seminars
“The Gurdon is my favorite institute in the UK” Edith Heard
The Gurdon Institute Seminar Series (see list below) is a well-established highlight of the academic year, bringing highprofile, international scientists before an audience drawn from across University biological sciences departments. Other seminars organised, co-organised or hosted by the Gurdon Institute for the local academic community during 2015 included: the Developmental Biology Seminar Series, the Gurdon
Institute Postdocs Association Seminar Series, Career Paths Workshops and one-day Retreat, Cambridge RNA Club, the Cambridge Advanced Imaging Lectures, Postdoc Masterclass for all Life Scientists, the Cambridge Fly Meeting, the Cambridge 3Rs (replication, repair, recombination) Seminar Series, and Worm Club. There were also ad-hoc internal, informal seminars from visiting scientists and alumni.
Gurdon Institute Seminar Series Lent and Easter terms 2015 20 January, Eileen Furlong, European Molecular Biology Laboratory, Heidelberg, Germany ‘Transcriptional regulation during developmental transitions: a view from 3D’ 3 February, Serena Nik-Zainal, Wellcome Trust Sanger Institute, Hinxton, Cambridge ‘Biological insights into mutagenesis through modern sequencing technologies’
During 2015 we passed the milestone of 2 million kWh of energy savings. 68 Activities and impacts in 2015
and mechanism of protein ubiquitination’ 24 March, Fiona Doetsch, University of Basel, Switzerland ‘Stem cells in the brain: Glial identity and niches’ 28 April (The Anne McLaren Lecture), Brigid Hogan, Duke University Medical Center, Durham, NC, USA ‘Stem cells in lung maintenance and repair’
24 February, David Barford, MRC Laboratory of Molecular Biology, Cambridge
19 May, Didier Stainier, Max Planck Institute for Heart & Lung Research, Bad Nauheim, Germany
‘The atomic structure of the APC/C: implications for understanding regulation
‘Imaging organ development and function in zebrafish’
Celebrations Green Impact street food party in August Energy-saving initiatives were implemented at the Gurdon Institute in 2012 after we became a pilot site for the University’s Energy and Carbon Reduction Project. With several Green Impact awards already under our belt from the University, our success continues: during 2015 we passed the milestone of 2 million kWh of energy savings. Annual retreat in October The retreat for scientific staff (photo on back cover) introduces new recruits to the full range of research projects throughout the Institute, with talks from all group leaders, and helps foster intellectual and social interactions. For 2015 we spent two days at the Five Lakes Hotel in Maldon, Essex, also enjoying team games, a poster session with prizes, and dinner with disco. Not forgetting: the BBQ house party in May and the much-anticipated Christmas parties, with a live band for the adults and a live Father Christmas for staff children and grandchildren. Michaelmas term 2015 6 October, Melina Schuh, MRC Laboratory of Molecular Biology, Cambridge ‘New insights into aneuploidy in mammalian oocytes’ 20 October, Buzz Baum, MRC Laboratory for Molecular Cell Biology, University College London ‘The logic and origins of eukaryotic cell organisation: Inside-out or outside-in?’ 3 November, Helen McNeill, Lunenfeld-Tanenbaum Research Institute, Toronto, Canada ‘Coordinating growth and tissue organisation during development’ 24 November, Edith Heard, Institut Curie, Paris, France ‘The relationships between chromosome structure and gene activity during X inactivation’ 1 December, Wendy Bickmore, MRC Human Genetics Unit University of Edinburgh ‘Gene regulation from a distance’
Acknowledgements Photo credits The front cover features a confocal image by Hannah Green (Brown group) of Drosophila indirect flight muscles mutant for the gene Vinculin (actin in red; the Z-line protein ZASP in green). Back cover: Peter Williamson. Portrait and group photos by James Smith, except pp. 10, 34, 36; p. 60 B. Simons: Royal Society; p. 61 S. Jackson: © FNRS/Aude Vanlathem; M. Wiese: EACR; p. 64: Hélène Doerflinger; p. 65: Royal Society; p. 66 plaque: Alzheimer’s Research UK; p. 67 Capella Building: Fairhursts Design Group; Daniel Zeichner: Steve Bond/Alzheimer’s Research UK; p. 69 John Overton. Production Claire O’Brien with Miranda Landgraf, Suzanne Campbell, Lynda Lockey and Ann Cartwright at the Gurdon Institute; and Claudia Flandoli (illustrations). Print management: H2 Associates, Cambridge.
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Wellcome Trust/ Cancer Research UK Gurdon Institute The Henry Wellcome Building of Cancer and Developmental Biology University of Cambridge Tennis Court Road Cambridge CB2 1QN, UK Tel: +44 (0)1223 334088 Fax: +44 (0)1223 334089 www.gurdon.cam.ac.uk contact@gurdon.cam.ac.uk