Chemistry and Structural Biology Research Title: Conotoxins that target chronic pain Group Leader: Paul Alewood Contact details: 3346 2982 or p.alewood@imb.uq.edu.au Website: http://www.imb.uq.edu.au/?page=11694 Summary of research interests: Our research focuses on identifying bioactive molecules from Australia’s venomous animals that have the potential to create drugs that will play important roles in finding treatments for chronic pain, heart disease, inflammation, irritable bowel syndrome, and breast cancer. Although toxins from these animals can have a devastating effect, molecules within them have been found to be useful in treating human disease. Specifically, we are interested in the discovery and total synthesis of potent and selective peptides (toxins) from venomous animals; the chemical synthesis of proteins and bioactive peptides; the development of new synthetic and analytical chemistry; and protein structure and function. Available honours projects: Conotoxins are small bioactive highly structured peptides from the venom of marine cone snails (genus) Conus which comprise 100-‐2000 distinct cysteine-‐ rich peptides for prey capture and defence. This project will focus on the discovery and characterisation of new conotoxins that are likely to target human receptors involved in chronic pain.
Research Title: Biodiscovery: Biodiversity and Biology, to Bioactives and Beyond Group Leader: Professor Robert Capon Contact details: Phone: 3346 2979 or r.capon@uq.edu.au Website: http://capon.imb.uq.edu.au Summary of research interests: My research group focuses on the detection, isolation, characterization, identification and evaluation of novel bioactive metabolites from Australian marine and terrestrial biodiversity. These metabolites span all known biosynthetic structure classes including many molecules new to science, and their study requires the use of sophisticated chromatographic, spectroscopic and chemical technologies. Natural products uncovered during our investigations represent valuable new leads in the search for drugs with application in the fields of human and animal health and crop protection, have potential as molecular probes to better interrogate and understand living systems, and could find application as biological control agents. Available Honours Projects Targeting Multidrug Efflux in Cancer: This project will develop our recent (unpublished) discovery of a marine fungal alkaloid that inhibit P-‐glycoprotein (P-‐gp) mediated multidrug resistance in human cancers. The project will optimize a practical synthesis, prepare a library of analogues, assess and document chemical properties and evaluate P-‐gp inhibitory activity against human colon cancer cell lines. Targeting Alzheimer’s Disease: This project will develop our recent (patented) discovery of a unique class of marine sponge alkaloid that inhibit kinases critical to the development of neurodegenerative diseases (e.g. Alzheimer’s). The project will optimize a practical synthesis, prepare a library of analogues, assess and document chemical properties and evaluate kinase inhibitory activity. Targeting Cane Toads: This project will develop our recent (patented) discovery of a pheromonal attractant capable of trapping cane toad tadpoles. The project will optimize the production and chemical derivatization of the pheromone, and the design and formulation of delivery devices, which will be evaluated in field trials
Research Title: Drug Discovery & Diagnostics Group Leader: Matt Cooper Contact details: 3346 2045 or info-‐coopergroup@imb.uq.edu.au Website: http://cooper.imb.uq.edu.au/ Summary of research interests: We believe that we can more effectively treat people by improving the way we understand and diagnose disease. Our research is aimed at discovering new ways of diagnosing and treating viral and bacterial infections, as well as diseases associated with chronic inflammation such as asthma, COPD, type II diabetes and cancer. We have a major focus on the design and development of novel antibiotics active against drug-‐resistant bacteria, also known as ‘superbugs’. Available honours: There are research projects available in the following areas: antibacterial and antifungal medicinal chemistry, small molecule inhibitors of inflammation, antibiotic mode of action studies, chemoinformatics, microbiology and nanotechnology for diagnostics.
Research Title: NMR spectroscopy Group Leader: Prof David Craik Contact details: 3346 2019 or d.craik@imb.uq.edu.au Website: http://www.imb.uq.edu.au/?page=11695 Summary of research interests: Our work focuses on applying NMR spectroscopy in drug design and development. By determining the structures of biologically active molecules it is possible to identify functional regions of these molecules and thus design novel drugs. We have a particular interest in stabilising proteins by joining their ends to make circular molecules. Available honours projects: • Discovery and structural characterisation of medicinal plant proteins, • Structure-‐activity studies of conotoxins, • Design of novel anticancer agents, • Protein engineering and drug design, • Molecular biology and evolution of cyclotides.
Research Title: Chemistry and human therapeutics Group Leader: David Fairlie Contact details: 3346 2989 or d.fairlie@imb.uq.edu.au Website: http://fairlie.imb.uq.edu.au/ Summary of research interests: Our group (http://fairlie.imb.uq.edu.au/) seeks to understand molecular mechanisms of chemical reactions, biological processes, disease development and drug action. Understanding how molecules interact, how chemical and biological reactions work, and how structure influences activity enables us to design, synthesize and evaluate enzyme inhibitors, receptor antagonists and protein-‐binding ligands as new drugs for cancer, infectious diseases, inflammatory disorders, diabetes and obesity, and Alzheimer’s disease. New drugs discovered by our chemists are studied by biochemists, cell biologists and pharmacologists in our group for their effects on human cells and in animal models of human diseases. Available Honours projects: • Drug design -‐ computer-‐assisted (molecular modeling, NMR structure determination), • Drug mechanisms of action (molecular pharmacology, cell biology, intracellular signalling studies), • Drug discovery -‐ chemical synthesis and structure (organic/medicinal chemistry), • Drugs in disease (experimental pharmacology, inflammatory diseases, metabolic diseases, diabetes, cancers, Alzheimer’s disease).
Research Title: Microbial structural biology and solar biofuels from algal cells Group Leader: Ben Hankamer Contact details: +61 7 334 62012 or b.hankamer@uq.edu.au Website: http://www.imb.uq.edu.au/structural-‐biology-‐of-‐membrane-‐ proteins-‐macromolecular-‐assemblies-‐and-‐viruses-‐ben-‐hankamer Summary of research interests: Our research focuses on the use of microalgae for the development of clean fuels to reduce CO2 emissions, increase energy security and enable sustainable economic development. Microalgae systems can use photosynthesis to convert solar to chemical energy for biomass and biofuel production and therefore are a promising platform for the production of renewable fuels as they can address the concerns related to the food vs. fuel conflicts. Light capture is the first step of photosynthesis so all biofuel production. Consequently its optimization is essential for the development of high-‐efficiency microalgal processes. The projects below use molecular biology, biochemistry and structural biology (predominantly electron cryo-‐microscopy) to guide the development of algal cells optimized in light capture. We are also interested in using cryoEM to study the structural basis of other microbial phenomena including virus infection and bacterial pathogenesis. Available honours projects: • Transcript and protein analysis of light harvesting complex proteins in the high hydrogen producing algal strain Stm6Glc4L01. This project is focused on improving solar driven H2 production from water using microalgae. • Structure analysis of high hydrogen producing algae strain Stm6Glc4L01 using electron microscopy. This project is focused on understanding the effect of light harvesting proteins on thylakoid membrane ultrastructure. • Isolation and structural characterisation of the Cyclic-‐electron flow – Photosystem I super complex using electron microscopy and single particle analysis. The recently discovered CEF-‐PSI complex is a ~1MDa membrane protein complex thought to regulate cyclic electron transport. Understanding its structure is important for the field of photosynthesis and renewable energy. • Towards high efficiency microalgae cultivation: This project involves pilot scale microalgae cultivation in raceway pond systems and/ or photo-‐ bioreactors and will involve biomass and water analyses. • Determining the structure of host endosomal sorting complexes (ESCRTs) that are hijacked during infection by enveloped viruses including HIV. Contact Dr Michael Landsberg (Email: m.landsberg@imb.uq.edu.au).
Research Title: Venomics as a drug and insecticide discovery platform Group Leader: Glenn King Contact details: Phone: 3346 2025 or glenn.king@imb.uq.edu.au Website: http://www.imb.uq.edu.au/index.html?page=56210 Summary of research interests: Animal venoms are increasingly important in drug discovery efforts as they constitute a vast and largely untapped source of pharmacologically active molecules. Spiders are by far the most successful group of venomous animals and their venoms are predicted to contain more than 10 million different biologically active peptides. Our group is exploring spider venoms as a source of novel peptides to provide leads for the development of ne drugs and insecticides. As a major part of this initiative, we have developed a structural venomics pipeline that allows protein structures to be determined via NMR at an unprecedented rate. Available Honours Projects • Screening spider venoms for peptides targeted at ion channels involved in sensing pain, and examination of their analgesic potential in animals. • Discovery of novel insecticidal and antimalarial compounds • Structural and functional characterisation of venom peptides • Characterisation of the interaction between venom peptides and their ion channel targets • Examination of the genetic basis underlying the remarkable diversity and evolution of venom peptides • Developing methods for automated protein structure determination via NMR.
Research Title: Molecular pharmacology of venoms Group Leader: Prof Richard Lewis Contact details: 3346 2984 or r.lewis@imb.uq.edu.au Website: http://www.imb.uq.edu.au/?page=11701 Summary of research interests: My group focuses on the discovery and biochemical characterisation of venoms and marine toxins, including conotoxins produced by cone snails to rapidly immobilise their prey, , and the ciguatoxins responsible for ciguatera. These toxins modulate a variety of membrane-‐bound proteins, including sodium and calcium channels, the nicotinic acetylcholine receptor (nAChRs), monoamine transporters and G-‐protein coupled receptors. Their high selectivity makes them important research tools and potential therapeutics. Through a multidisciplinary research program, including peptide and target SAR, we are further developing the potential of these interesting molecules, particularly in the area of pain research. Available honours projects: Interested applicants are encouraged to seek further details by contacting Prof Richard Lewis r.lewis@imb.uq.edu.au
Research Title: Protein crystallography and drug design Group Leader: Prof Jenny Martin Contact details: 3346 2016 or j.martin@imb.uq.edu.au Website: http://www.imb.uq.edu.au/protein-‐structure-‐drug-‐design-‐jenny-‐ martin Summary of research interests: Antibiotic resistance is a serious and growing problem in modern medicine; as more bacteria develop multidrug resistance, fewer new antibiotic drugs are being brought to market, creating the ‘perfect storm.” Where is the next antibiotic going to come from? Many bacteria encode a family of DSB (DiSulfide Bond) proteins that are essential for bacterial virulence because they add structural bracing to secreted and membrane-‐integral virulence factors. Little is known about how this DSB protein machinery operates in the human pathogen Pseudomonas aeruginosa. Characterisation of DSB proteins in this pathogen, particularly the membrane protein DsbB, using bioinformatics, structural biology and biochemical approaches will enable us to expand our knowledge of bacterial pathogenicity and could underpin structure-‐based drug design of new bacterial inhibitors. Available honours projects: Interested applicants are encouraged to seek further details by contacting Prof Jenny Martin on j.martin@imb.uq.edu.au
Research Title: Combinatorial chemistry and molecular design Group Leader: Prof Mark Smythe Contact details: 3346 2977 or m.smythe@imb.uq.edu.au Website: http://www.imb.uq.edu.au/?page=11703 Summary of research interests: Many biological processes are carried out, or regulated, through protein-‐protein interactions. Despite their physiological significance, they remain one of the most difficult molecular recognition events to inhibit or mimic. Consequently there is a huge pharmaceutical demand for the discovery of small molecules that modulate protein function. We are developing methodologies for the discovery of small molecule protein mimetics by studying the chemical and conformational diversity of protein surfaces to provide better candidates for the development of leads for protein-‐protein interaction targets. Projects are offered in the disciplines of drug design, mathematics, chemistry and biology, as related to the development of drugs for specific therapeutic targets. Specifically this includes the development of new drugs for cancer, asthma, bacterial infection and inflammatory disorders. Available honours projects: • High-‐throughput sequencing to identify, describe and diagnose previously inexplicable leukodystrophies, • Development of bioinformatics tools to reveal rare Mendelian variants associated with paediatric disorders, • Development of tools and approaches to understand the effect of novel variants.
Genomics and Computational Biology
Research Title: Pattern recognition and computational biology Group Leader: Dr Tim Bailey Contact details: 3346 2614 or t.bailey@imb.uq.edu.au Website: http://www.imb.uq.edu.au/pattern-‐recognition-‐and-‐modelling-‐ in-‐computational-‐biology-‐tim-‐bailey Summary of research interests: Our group develops and applies pattern recognition algorithms for computational biology. We are particularly interested in aiding the elucidation of the mechanisms of genetic regulation. We are developing algorithms to identify transcription factor binding sites and search for cis-‐regulatory modules. To do this, we leverage many techniques in probabilistic modelling and machine learning. These include hidden Markov models and support vector machines. We are also interested in mining genome and transcriptome databases for biological knowledge. To do this, we utilise a wealth of existing bioinformatics tools, as well as develop new ones. Available honours projects: Interested applicants are encouraged to seek further details by contacting Dr Tim Bailey t.bailey@imb.uq.edu.au
Research Title: Population genomics Group Leader: Lachlan Coin Contact details: 3346 2649 or l.coin@imb.uq.edu.au Website: http://www.imb.uq.edu.au/lachlan-‐coin Summary of research interests: The initial sequencing of plant and animal genomes, including the human genome, accomplished approximately 10 years ago, has led to remarkable discoveries about the genomic relationships between species, and into evolutionary history and processes. We are now entering a population sequencing era in which thousands of genomes from these species are being sequenced. This data will enable us to map genomic variation within species, and assess the phenotypic impact of this variation. My group is particularly interested in mapping genomic structural variation, including copy number variation, repeat variation and balanced structural variation such as translocations and inversions. We are developing algorithms for mapping this variation from next-‐generation sequence data. Available honours projects: • Algorithmic development, particularly for identification and genotyping of tandem repeats and inversions from low-‐coverage population sequence data, • Mapping structural variation in multiple plant and animal genomes, including sheep, rice, and human data, • Investigating population differentiation and positive selection of structural variation in humans.
Research Title: Modelling, Visualisation and Classification of Bio-‐Imaging Group Leader: Dr Nick Hamilton Contact details: 3346 2033 or n.hamilton@uq.edu.au Website: http://www.imb.uq.edu.au/index.html?page=91481 Summary of research interests: Bio-‐imaging is undergoing rapid growth. High throughput screens for drug and genomic discovery are leading to massive image sets in need of new methods of modelling, analysis, classification, feature extraction, organisation, visualisation, comparison, hypothesis testing and inference. The core of the groups research is to develop the methodologies, algorithms and tools to maximise the benefit of the new data sources becoming available. The group collaborates closely with cell biology, bioinformatics and mathematics groups in creating these methodologies and utilises and develops techniques in areas such as machine learning, data clustering, graph algorithms, image segmentation, statistical testing and mathematical modelling. Available honours projects: Projects areas include: • Mathematical modelling of biological systems from microscopy imaging •
Information visualisation and clustering methodologies
See Hamilton Lab's web site for further information on the group and its interests or contact Nick to discuss ideas for projects.
Research Title: Expression genomics Group Leader: Prof Sean Grimmond Contact details: 3346 2057 or s.grimmond@imb.uq.edu.au Website: http://www.imb.uq.edu.au/expression-‐genomics-‐sean-‐grimmond Summary of research interests: Next-‐generation sequencing of tumours is providing researchers with a better understanding of the molecular changes which occur during tumourigenesis. Cataloging these events, which are present in individual tumours, and identification of tumour-‐specific pathways will enable targeted therapy to become a reality. Pancreatic cancer is an aggressive form of disease with a median survival of six months. Less than 5 percent of patients will survive beyond five years. Current treatment options for pancreatic cancer are limited, and alternative therapies need to be identified. As part of the International Cancer Genome Consortium (ICGC) we will be sequencing the genome, transcriptome and epigenome of 350 pancreatic tumours and matched normal samples. There are a variety of projects available for students interested in cancer genomics including laboratory validation of findings from the ICGC project and the computational analysis of next-‐generation sequence data. Available honours projects: Interested applicants are encouraged to seek further details by contacting Dr Nic Waddell -‐ n.waddell@imb.uq.edu.au
Research Title: Comparative and computational genomics Group Leader: Prof Mark Ragan Contact details: 3346 2616 or m.ragan@imb.uq.edu.au Website: http://www.imb.uq.edu.au/computational-‐genomics-‐mark-‐ragan Summary of research interests: We use advanced computing and bioinformatics to make quantitative inferences about how genomes, gene families, protein families and biomolecular networks evolve, diversify and function in mammalian cells and in bacteria. Available honours projects: Honours projects could include data integration, data analysis and/or computational inference for: • Gene exchange and genetic recombination in pathogenic bacteria, • Gene exchange and genetic recombination across entire microbial ecosystems, • Genes for brain development, social behaviour and cognition in the Neandertal genome • Networks of molecular interactions and genetic regulation in cancer, • Protein interaction domains and the evolution of new cellular functions. Some project areas require expertise in scripting/coding eg. in Python, Perl, Java, Matlab or R.
Research Title: Deciphering the unconventional genetics of complex life and inherited disease Group Leader: Dr Ryan Taft Contact details: 3346 2080 or r.taft@imb.uq.edu.au Website: http://www.imb.uq.edu.au/?page=172333 Summary of research interests: My lab uses the latest hardware, software and laboratory technologies to answer pressing biological and medical questions, with the hope of explaining fundamental genetic processes and unravelling previously mysterious inherited diseases. We are currently focused on two key areas: (1) the role of RNA in the regulation of epigenetics, and (2) the use of high-‐ throughput DNA sequencing technologies to identify genes disrupted in childhood neurodevelopmental disorders. To tackle both of these problems, we use a combination of bioinformatics, molecular genetics and biochemistry -‐ our team is made up of both hard-‐core programmers and scientists with more than 30 years of laboratory bench experience. While the short-‐term aim is to tackle each of these projects on their own merits, the lab’s long view is that eventually we will be able to combine our knowledge of the RNA world, its influence on epigenetics and whole-‐genome sequencing to completely understand (and in some cases diagnose) a range of inherited and acquired illnesses. Available honours projects: • The characterisation of tiny RNAs and other chromatin-‐associated RNA species using high-‐throughput sequencing and various RNA capture methodologies, • Expression and functional analysis of sno-‐derived RNAs (sdRNAs) associated with the Prader-‐Willi Syndrome locus
Molecular Cell Biology
Research Title: Molecular engineering: Better tools, better science, better life Group Leader: Kirill Alexandrov Contact details: 334 62397 or k.alexandrov@imb.uq.edu.au Website: http://www.imb.uq.edu.au/?page=83129 Summary of research interests: The ability to replicate the building blocks of life, such as DNA and proteins, represents the core technologies of life sciences. The exponential increase in the number of sequenced genomes has focused attention on how best to produce, study and modify the encoded gene products. While the structural and functional information is encoded in single protein molecule, accessing this information is technically and economically challenging. This constitutes a critical technological bottleneck that determines the pace of progress in many areas of biology and biotechnology. The problems become particularly aggravating when analysis of complex protein machines is attempted. We are working on the approaches that allow rapid and flexible production, analysis and engineering of proteins and protein complexes. By integrating cell-‐free protein production, microfluidic handling and single molecule fluorescence spectroscopy we develop new processes for understanding the complex molecular machines such as tethering complexes and transcription regulating complexes. Further we use the developed technologies for construction of novel biological module and cascades. Available honours projects: • Development of approaches for recombinant production and biophysical analysis of multi-‐subunit protein complexes, • Quantitative analysis of protein:protein protein:small molecule interactions using a novel in vitro translation system, • Development of high-‐yield eukaryotic protein expression systems based on protozoan Leishmania tarentolae, • Development of synthetic protein receptors and signal amplification cascades.
Research Title: Structural biology of membrane trafficking and remodeling Group Leader: Dr. Brett Collins Contact details: 3346 2043 or b.collins@imb.uq.edu.au Website: http://www.imb.uq.edu.au/?page=82433 Summary of research interests: Our group studies the fundamental process of protein transport in the human cell. In particular, we aim to determine the molecular basis of how protein coats bind to receptors such as the amyloid precursor protein involved in Alzheimer’s and control their packaging into membrane-‐bound vesicles. We use a wide variety of techniques including molecular biology, protein X-‐ray crystallography, biochemical and biophysical studies of protein-‐protein and protein-‐lipid interactions, and cellular studies of protein localisation to build coherent molecular models of how molecules are trafficked within the cell. Available honours projects: • Determining structures of novel proteins involved in cellular trafficking by X-‐ray crystallography. • Biochemically characterize how specific membrane lipids regulate protein recruitment to cellular organelles.
Research Title: The cell surface in health and disease Group Leader: Prof Rob Parton Contact details: 3346 2032 or r.parton@imb.uq.edu.au Website: http://www.imb.uq.edu.au/?page=11688 Summary of research interests: Our research focuses on the organisation, dynamics, and functions of the plasma membrane. We use electron microscopy, real-‐time light microscopy, molecular biology, and biochemistry to examine the dynamics and microdomain organisation of the plasma membrane, especially the function of domains termed caveolae. These are involved in signal transduction and lipid regulation and have been linked to disease states such as muscular dystrophy and cancer. Available honours projects: • The role of caveolae in the zebrafish, • Functional analysis of mutations in caveolin-‐3 associated with muscular dystrophy
Research Title: Inflammasomes in infection and inflammatory disease Group Leader: Dr Kate Schroder Contact details: 3346 2058 or K.Schroder@imb.uq.edu.au Website: http://www.imb.uq.edu.au/index.html?page=156078 Summary of research interests: The innate immune system is critical to defence against infection, but also drives unhealthy processes in inflammatory disease. An important emerging player in innate immunity in both of these settings is the ‘inflammasome’ pathway. Inflammasomes are molecular machines that trigger cytokine maturation and immune system activation in response to signals indicating cellular ‘danger’. While the inflammasome pathway is critical for host defence against infection, it is also a key driver of unhealthy inflammation in many human diseases. We use a wide variety of molecular and cell biology techniques, in conjunction with animal models and human clinical samples, to investigate the biology of inflammasomes in host defence and inflammatory disease at the molecular, cellular and organismal levels. Available honours projects: Interested applicants are encouraged to seek further details by contacting Dr Kate Schroder k.schroder@imb.uq.edu.au
Research Title: Protein trafficking in inflammation and cancer Group Leader: Prof Jenny Stow Contact details: 3346 2159 or j.stow@imb.uq.edu.au Website: http://www.imb.uq.edu.au/?page=11689 Summary of research interests: We study the sorting, intracellular trafficking and secretion of biologically and medically important proteins using advanced cell and molecular biology techniques including fluorescence imaging, gene expression and RNAi. Key trafficking pathways in macrophages ensure that invading microbes are eaten or phagocytosed and that the cells respond by secreting cytokines, antimicrobial peptides and other factors to fight infection and to mount protective inflammatory responses. These same processes go awry in some infectious diseases and in inflammatory disease. Our studies are aimed at defining the relevant genes, proteins, cell compartments and potential drug targets. We are also interested in cellular mechanisms for sorting and polarity of protein secretion in macrophages, epithelial cells, cancer cells and other cells. We study individual trafficking genes and proteins and take a more systems-‐based approach to studies on whole families of trafficking proteins. Available honours projects: • Fluorescent imaging of cytokines in live macrophages; identification of Rabs, SNAREs and other trafficking genes, • Phagocytosis and endocytosis of bacteria by macrophages; host-‐pathogen interactions, • Endosome function in secretion; sorting and the immune response, • Protein sorting and cell polarity in epithelia and cancer.
Research Title: Pathogen surveillance, innate immunity and inflammation Group Leader: Dr Matt Sweet Contact details: 3346 2082 or m.sweet@imb.uq.edu.au Website: http://www.imb.uq.edu.au/index.html?page=64297 Summary of research interests: My group studies the innate immune system. Innate immune cells, such as macrophages, express a broad repertoire of pattern recognition receptors. For example, members of the Toll-‐like Receptor (TLR) family detect a number of pathogen-‐associated molecular patterns such as LPS from Gram-‐negative bacteria. Macrophage activation through TLRs regulates expression of genes involved in antimicrobial responses and inflammation. Thus, TLR signaling is required for effective control of invading microorganisms, but if dysregulated, contributes to acute and chronic inflammatory diseases. We study TLR signalling pathways and the function of novel TLR-‐regulated genes in inflammation and in responses to bacterial pathogens (e.g. Salmonella). Available honours projects: • Role of protein deacetylases in promoting TLR-‐mediated inflammation • The role of zinc and TLR-‐regulated zinc trafficking in human macrophage responses to bacterial pathogens • Mechanisms of macrophage pyroptosis triggered by uropathogenic E. coli • Functional analysis of novel TLR target genes.
Research Title: Endosomal Dynamics and Pathogen Invasion Group Leader: Dr Rohan Teasdale Contact details: 3346 2056 or r.teasdale@uq.edu.au Website: http://www.imb.uq.edu.au/index.html?page=11682&pid=11669 Summary of research interests: The endosomal/lysosomal system of mammalian cells is a highly dynamic organelle and the trafficking pathways within the endosomal system are fundamental for a wide variety of key cellular processes. My group is developing cellular and computational approaches to identify novel mammalian proteins associated with the endosomal system. This includes the retromer complex that has recently been identified as a causal agent for Type 2 diabetes and neurodegenerative disease. Numerous infectious pathogens exploit specific endocytic pathways to invade the host. Characterization of pathogen entry pathways is essential for understanding infectious diseases but has also proven to be a powerful tool for gaining insight into normal cellular processes. We are currently investigating the molecular details of these pathways and how they are modulated in response to infection with Salmonella, a leading cause of human gastroenteritis and Chlamydia a major sexually transmitted pathogen. Once inside the cell, these pathogens actively alter the host cells membrane trafficking pathways to create a replicative niche that enables the pathogen to survive and avoid the innate immune system in these cells. Available honours projects: •
• •
Defining the essential host proteins required for intracellular bacterial pathogen infection. These host proteins represent attractive therapeutic targets. RNAi screening to further define essential proteins for a range of endosome associated pathways targeted by bacterial pathogens. Define defining the molecular and cellular properties of retromer’s function in neurodegenerative diseases including Parkinson’s and Alzheimer’s.
Research Title: Growth hormone action and cytokine signalling Group Leader: Mike Waters Contact details: 3346 2037 or m.waters@imb.uq.edu.au Website: http://www.imb.uq.edu.au/?page=11721 Summary of research interests Postnatal growth is a complex process driven by growth hormone (GH). GH also regulates carbohydrate, lipid and phase1/2 hepatic metabolism. Absence of GH results in lifespan extension in mice and no deaths due to cancer or diabetes in humans. We study the mechanistic basis for these actions at all levels. Of particular interest is determining the molecular movements responsible for receptor activation of JAK-‐STAT signalling, and extending our model of this to other cytokine receptors. We also study why GH is essential for cancer progression, particularly prostate cancer, and how it promotes fat burning and opposes obesity using genetically engineered mouse models, microarrays and viral transduction. Available honours projects: • Molecular mechanism for activation of the receptor by GH and coupling to JAK2 and Src kinase activation, • Role of GH/STAT5 in preventing obesity, • Role of GH/STAT5 in promoting cancer, • Role of GH/STAT5 in promoting diabetes, • Mechanism of longevity conferred by loss of GH-‐dependent STAT5 signalling, • Mechanism of signalling by GH receptor directly in the nucleus and its relation to cancer progression.
Research Title: Cadherin signalling and morphogenesis Group Leader: Dr Alpha Yap Contact details: 3346 2013 or a.yap@imb.uq.edu.au Website: http://www.imb.uq.edu.au/?page=11722 Summary of research interests: My group studies the morphogenetic mechanisms of cadherin adhesion molecules. These cell surface receptors are key determinants of tissue patterning during development and wound healing. Importantly, cadherin dysfunction is a major factor in common human diseases, such as tumour invasion and epithelial inflammation. We believe that understanding the cell and molecular mechanisms by which cadherins control normal tissue patterning will provide valuable insights into how cadherin dysfunction contributes to disease. A major focus of our work lies in understanding how cadherin signalling regulates the cytoskeleton, and the morphogenetic impact of these processes, especially through control of contractile forces at cell-‐cell junctions. Available honours projects: Potential honors projects are based on current developments in the group; indicative projects include: • How junctional mechanics contributes to tumor cell invasion. • Cell-‐cell junctions and cell migration.
Molecular Genetics and Development
Research Title: The lymphatic vascular tree in development and disease Group Leader: Dr Mathias Francois Contact details: 3346 2060 or m.francois@imb.uq.edu.au Website: http://www.imb.uq.edu.au/index.html?page=167712 Summary of research interests: My research program is designed to identify and characterise key transcriptional pathways that modulate lymphatic vascular development in the mouse embryo. We are interested in translating our discoveries in pre-‐clinical mouse models of cancer or lymphedema in order to validate the central role of developmental programs that are re-‐activated under these pathological conditions. Ultimately we aim to develop a novel class of compounds that will enable the pharmacological management of the lymphatics with the view to probing vascular development or setting up the basis for drug development. The experimental strategies we have developed to perform this translational research program rely on a pipeline of assays ranging from in vitro analysis (fluorescence polarisation, cell-‐based assays) to in vivo mouse models (melanoma xenograft) and involve tight collaborations with other IMB scientists and international research groups who are experts in zebrafish biology, medicinal chemistry and in vivo live imaging. Available honours projects: • Analysis of the transcriptional network that governs lymphatic endothelial cell fate (mouse genetics), • Molecular characterisation of the embryonic pathways re-‐activated in lymphatics during cancer metastasis (pre-‐clinical models), • Validation of novel molecular targets and assessment of their druggability to develop novel anti-‐cancer agents
Research Title: Molecular genetics of vascular development Group Leader: Dr Ben Hogan Contact details: 3346 2105 or b.hogan@imb.uq.edu.au Website: http://www.imb.uq.edu.au/?page=117835 Summary of research interests: My group studies the development of the embryonic vasculature with a focus on the discovery of novel genes involved in blood and lymphatic vessel development in the embryo. We are particularly interested in the development of lymphatic vessels, as the lymphatic vasculature plays critical roles in several human diseases and is a validated target for the inhibition of cancer metastasis. We study the processes of cell fate specification, precursor cell migration and the differentiation of vascular endothelial cells using the zebrafish embryo as a model system. The approaches we use include molecular genetics (mutant identification and characterisation, as well as the analysis of key genes of interest) and high-‐resolution in vivo imaging of the cellular processes driving the development of the vasculature in the embryo. Ultimately, we aim to elucidate molecular and cellular mechanisms that control vessel development and to understand how the pathways and processes we identify contribute to human disease. Available honours projects: • Analysis of signalling pathways in lymphatic vascular development in zebrafish, • Molecular characterisation of novel zebrafish mutants that fail to form lymphatic vessels. • Generation of transgenic lines to label and image cells of the developing vasculature.
Research Title: Molecular genetics of mammalian development Group Leader: Prof Peter Koopman Contact details: 3346 2059 or p.koopman@imb.uq.edu.au Website: http://www.imb.uq.edu.au/?page=12016 Summary of research interests: Work in my laboratory is aimed at isolating genes involved in cell differentiation and organogenesis, and studying their expression, regulation, function and interaction in the mammalian embryo, using mice as an experimental model. Areas of special interest include sex determination, gonadal organogenesis and germ cell development. Aside from the basic science of understanding the molecular and cellular events underpinning these processes, this work is increasingly being applied to medical and biotechnological outcomes, namely the understanding and management of human genetic disorders (including sex disorders, fertility management and cancer) pest and livestock biotechnology, stem cell biology, regenerative medicine, drug discovery and novel routes to transgenesis. Available honours projects: • Identification and functional study of sex-‐specific genes, • Control of meiosis in germ cells
Research Title: Renal development, disease and regeneration Group Leader: Prof Melissa Little Contact details: 3346 2054 or m.little@imb.uq.edu.au Website: http://www.imb.uq.edu.au/kidney-‐development-‐damage-‐repair-‐ and-‐regeneration-‐melissa-‐little Summary of research interests: The kidney is a complex but vital organ that not only filters the blood to produce urine but also regulates blood pressure, red blood cell production and produces hormones and growth factors. If your kidneys fail, current treatment involves long-‐term dialysis or organ transplantation, both of which have considerable side effects. As the prevalence of chronic renal failure is increasing at 7 percent per annum, this provides a strong imperative to the development of novel therapies. There is also a growing awareness that your individual predisposition to renal failure can be determined in utero, in that the number of functional units (nephrons) per kidney is inversely related to renal function later in life. The projects underway in my laboratory all focus around the kidney, and cover molecular developmental biology, stem cell biology and experimental nephrology. By understanding how the kidney arises in the first place, what can go wrong during development and what can go wrong to give you renal disease, we hope to progress novel approaches to treatment. This involves understanding the progenitors that give rise to the kidney, how the kidney responds to damage and whether renal stem cells remain in the adult kidney. With the advent of reprogramming technology, we also have an interest in recreating renal stem cells or differentiating embryonic stem cells to renal progenitors. Available honours projects: • Modelling cell turnover in the developing kidney, • Analysis of the effect of hypoxia on nephrogenesis, • Characterisation of adult renal stem cells.
Research Title: Nuclear receptors and metabolism Group Leader: Prof George Muscat Contact details: 3346 2222 or g.muscat@imb.uq.edu.au Website: http://www.imb.uq.edu.au/?page=11687 Summary of research interests: Our research focuses on elucidating the functional role of nuclear hormone receptors in the regulation of metabolism in the context of metabolic disease (e.g. dyslipidaemia, diabetes and obesity) and breast cancer. The nuclear hormone receptors (NR) belong to a superfamily of hormone-‐dependent DNA binding factors that translate pathophysiological, metabolic, and nutritional signals into gene regulation. Dysfunctional NR signalling results in obesity, type 2 diabetes and cancer Metabolic disease increase the risk and incidence of cancer. The significance of NRs in human health is emphasised by the array of pharmaceuticals that target NRs in the context of reproduction, inflammation, metabolic and endocrine diseases. The majority of our research is focused on skeletal muscle, for example, NRs are expressed in skeletal muscle, a peripheral tissue that accounts for ~40 percent of the total body mass and energy expenditure, and is a major site of fatty acid and glucose oxidation. Consequently, muscle has a significant role in insulin sensitivity, the blood lipid profile, and energy balance. Therefore, it is not surprising that NRs and skeletal muscle are emerging as targets in the battle against metabolic disease. The objective of our current research is to examine the role of ‘orphan’ NRs in metabolic disease, and breast cancer. We are testing the hypothesis that the orphan NRs, for example RORs and NR4As, control pathophysiological process in metabolic disease and cancer. Available honours projects: • Understanding resistance to diet-‐induced obesity and fatty liver disease in ROR-‐deficient mice, • Understanding the role of the adrenergic sensitive NR4A receptors in endurance exercise and resitance to diet induced obesity • Analysing the role of chromatin remodeling enzymes (histone methyltransferases) in glycogen metabolism and storage diseases.
Research Title: Cardiac development and disease Group Leader: Dr Kelly Smith Contact details: 3346 2050 or k.smith@imb.uq.edu.au Website: http://www.imb.uq.edu.au/smith Summary of research interests: My research aims to understand how to build a heart. The heart is critical for our survival and any structural mistakes (collectively known as Congenital Heart Defects) or any failure to restore cardiac function (resulting in heart failure) is catastrophic for survival. In order to repair such defects, we first need to understand how the heart is formed. Every time an embryo develops, it makes a heart, and we hijack this process to study heart organogenesis. Using the translucent zebrafish model, we employ fluorescent transgenic reporter strains and genetic mutant lines to interrogate the cellular and genetic regulation of cardiac morphogenesis. These tools allow us to watch the heart as it develops in real-‐time and to determine which genetic defects impact on cardiac development. Understanding how the heart develops and what can go wrong is the first step toward understanding repair-‐based therapies. Available honours projects: • Generation and characterisation of novel cardiac transgenic lines, • Positional cloning and characterisation of zebrafish cardiac mutants, • Dissecting the role of the valve primordium in cardiac morphogenesis.
Research Title: Molecular genetics of pigmentation and melanoma Group Leader: Dr Rick Sturm Contact details: 3346 2038 or r.sturm@imb.uq.edu.au Website: www.imb.uq.edu.au/index.html?page=11690 Summary of research interests: Melanocytes produce the melanin pigments responsible for skin, hair and eye colour. Darker forms of melanin protect the skin from solar radiation exposure, however melanocytes are also the cell type from which malignant melanoma can originate. We are studying the human pigmentation system to understand the genetic basis of cellular differentiation, tissue-‐specific gene expression and cellular transformation induced by solar UV light. Available honours projects: • Genetics of human pigmentation including comparing individuals of high and low mole number, and looking at genes controlling mole morphology, • Cell biology of human pigmentation, whereby the laboratory is growing primary cultures of human melanocytes alone or together with keratinocytes to assay function of genes
Research Title: Molecular genetics of human diseases Group Leader: Prof Brandon Wainwright Contact details: 3346 2053 or b.wainwright@imb.uq.edu.au Website: http://www.imb.uq.edu.au/?page=11673 Summary of research interests: Our research group focuses on understanding the mechanism of common human cancer. In particular we study the paediatric brain tumour, medulloblastoma, and the most common form of cancer, basal cell carcinoma of the skin (BCC). Both of these tumour types are caused by aberrant regulation of the Hedgehog (Hh) signalling pathway. The Hh pathway is also important in normal embryonic development and stem cell regulation. Therefore, our work examines both the cancerous state and normal tissue regulation. We work at the interface between developmental biology and human/mouse genetics and genomics to gain new insights into how cancers occur, and how we might block their growth. Available honours projects: Projects in the area of control of tumour and stem cell growth will be offered.
Research Title: Developmental genes and human disease Group Leader: Prof Carol Wicking Contact details: 3346 2052 or c.wicking@imb.uq.edu.au Website: http://www.imb.uq.edu.au/?page=11691 Summary of research interests: Our research focuses on the role of the primary cilium in embryonic development and human disease. Over the past decade the primary cilium has emerged as a pivotal cellular organelle essential for the regulation of key embryonic signalling pathways. Dysfunction of this organelle is responsible for an expanding class of human congenital diseases collectively known as ciliopathies. Patients with these disorders have widespread defects, and we are interested in a specific subclass with skeletal anomalies. We combine mutation analysis in families with ciliopathies, with functional studies in animal and cell-‐ based models to investigate the mechanism of disease. Available honours projects: • Characterisation of novel mouse models of ciliopathies, • Functional analysis of novel skeletal cilopathy genes arising from whole-‐ exome sequencing