Advanced studies projects 2014

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Project Title: Developing a high throughput screen for small molecule modulators of class I cytokine receptor signalling. Supervisor: Dr Andrew Brooks and Prof Mike Waters Contact: a.brooks@uq.edu.au and m.waters@uq.edu.au Class I cytokine receptors such as the Growth Hormone, Prolactin, and Erythropoietin Receptor regulate a diverse range of biological processes. Small molecules that can modulate the signalling pathways from this important class of receptors can lead to the development of many potential medically relevant outcomes. The development of a high throughput screen will be a critical requirement for identifying effective biologically active molecular modulators of Class I cytokine receptor signal transduction. Project title: Identification of bioactive compounds from Queensland plants. Supervisor: Dr Mark Butler (Cooper Lab, IMB) Contact: email: m.butler5@uq.edu.au As part of an ongoing efforts to identify new anti-infective leads, we will screen pre-selected Queensland plants for antifungal, antibacterial and cytotoxicity activity. Once active extracts are identified bioassayguided isolation will be used to identify the active components. The structures of these bioactive compounds will be determined using spectroscopic techniques that include NMR and MS. This project would suit students interested in analytical/organic chemistry and anti-infective lead discovery Project title: Cane Toad Chemical Ecology: An Attractive Solution Supervisor: Professor Rob Capon Contact: r.capon@uq.edu.au ph 334 62979 We recently published [1] the molecular structure of a natural attractant pheromone present in cane toad eggs, and invented [2] a bait/trap design capable of attracting and selectively eliminating cane toad tadpoles from the wild. This project provides an opportunity for a student to participate in the harvest and chemical analysis of attractant from dead adult cane toads and egg masses, to optimize the design of baits to be used in trapping campaigns. [1] Crossland, M. R., Haramura, T., Salim, A., Capon, R. J. and Shine, R. (2012). "Exploiting intraspecific competitive mechanisms to control invasive cane toads (Rhinella marina) " Proc. R. Soc. B: online June 13, 2012. [2] Patent, Chemical attractant and use thereof, Australia, (2012) The University of Queensland and The University of Sydney, 2012902386

Project title: Mapping repeat variation in the Tuberculosis genome using next generation sequencing Supervisor: Lachlan Coin Contact: email: l.coin@imb.uq.edu.au phone: 334 62649 Mycobatericum tuberculosis (Mtb) caused 1.7 million deaths globally in 2009 and is estimated to be the largest cause of infectious disease mortality in Papua New Guinea (PNG), our nearest neighbour , despite being a treatable disease. This is associated with an increase in the prevalence of multi-drug resistant (MDR) and extreme multi-drug resistant (XDR) Mtb . In order to treat patients effectively, it is first necessary to type the strain of Mtb and to identify drug resistance. Strain typing is typically done using a panel of variable number tandem repeats, and drug resistance testing is carried out experimentally. Next generation sequencing has the potential to revolutionise Mtb strain typing and prediction of drug resistance. This project will focus on developing and applying methodology for genotyping tandem repeat variation in Mtb genomes. The methodology will be applied to Mtb sequence data collected from patients from Papua


New Guinea, and will be validated against traditional genotyping approaches and drug resistance testing carried out by the Queensland Mycobacterium reference laboratory. Background required: Mathematics, physics or computer science Project title: Why are proteins necessary for cell division also used at cell-cell junctions between nondividing cells? Supervisors: Dr Srikanth Budnar & Prof Alpha Yap Contact: email: s.budnar@imb.uq.edu.au or a.yap@uq.edu.au Epithelia are comprised of sheets of cells that are physically linked together by cell-cell adhesion systems. These adhesion systems, such as the canonical E-cadherin system, are essential for the developmental generation of epithelia and for their function in post-developmental life. This is exemplified by the fact that dysfunction of E-cadherin promotes cancer progression to invasion and metastasis. We now understand that the physiological function of E-cadherin is not just due to the adhesion receptor itself. Instead, it reflects the ability of E-cadherin to functionally and biochemically integrate with cell signaling and the intracellular actin cytoskeleton. Surprisingly, though, we are starting to discover that many of the key proteins that regulate cell-cell junctions in non-dividing cells are also used during cell division, when cell-cell junctions break down. Why this is so is unknown, but is likely to reflect some fundamental coordination of signaling and the cytoskeleton during, and between, cell divisions. We have discovered that the protein, anillin, possesses exactly this behavior and are now seeking to understand why it behaves like this. Anillin is a multi-domain protein that can interact with a range of other molecules, notably signaling molecules and the actin-myosin cytoskeleton. In this project we are using mutagenesis to investigate the intermolecular interactions that contribute to the function of anillin at E-cadherin junctions. (4) Cell-cell adhesions and the junctional cytoskeleton in epithelial carcinogenesis Supervisors: Dr Carol Au & Prof Alpha Yap Contact: email: c.au@uq.edu.au or a.yap@uq.edu.au Cells of the body are organised into coherent populations through dynamic cell-cell interactions. Our research focuses on the epithelium, which forms the protective cell layer of our body and is the most common source of cancers. Specifically we study the E-cadherin adhesion receptor that mediates epithelial cell-cell interactions, as well as regulation of the actin cytoskeleton. This project will examine how oncogenic genes may perturb cadherin adhesions and the actin cytoskeleton in breast epithelial cells, which will have implications towards our understanding of breast cancer progression. It will involve molecular and cell biology techniques, including cell culture and fluorescence microscopy. Prof Ben Hankamer, Dr Ian Ross Nad Dr Michael Landsberg have several projects: 1. Single particle analysis of microalgae photosynthetic complexes. 2. Biochemical analysis of microalgae photosynthetic complexes. 3. Development of an automated nutrient screen for marine algae strains. 4. Bio business development: microalgae market analysis. 5. Developing novel flow cytometry assays for monitoring algal physiology at the Solar Biofuels Research Centre 6. Analysis of cyclic electron transport in microalgae using pulse amplitude modulated (PAM) fluorometry


Contact details: b.hankamer@uq.edu.au: i.ross@imb.uq.edu.au or m.landsberg@uq.edu.au

Project Title: Specific and Efficient Anti-Inflammatory Treatment for Asthma Supervisor: Dr Christina Kulis and Prof Mark Smythe Contact: c.kulis@imb.uq.edu.au Brief Project Description: Our research team is focused on drug design using a plethora of medicinal chemistry techniques, including molecular modeling, virtual screening, synthetic organic chemistry, peptide chemistry and biological assays. This multidisciplinary project is focused on the development of specific small molecule inhibitors of human prostaglandin D2 synthase (HPGD2S) for the tr eatment of asthma. Project title: Genome-scale analysis of genetic exchange in microbes Supervisors: Prof. Mark Ragan, Dr Cheong Xin Chan, Dr Leanne Haggerty Contact details: m.ragan@imb.uq.edu.au, c.chan1@uq.edu.au, l.haggerty@imb.uq.edu.au Genome sequencing is increasingly being applied in microbiology to characterise pathogens, to understand patterns of transmission and development of antibiotic resistance, and to identify response measures. Skills in data management, computing and analysis are however not taught in sufficient detail as a routine part of most undergraduate programs in life sciences. Skills in computational analysis of genome-scale datasets will be an important asset to young researchers planning an internationally competitive career in the life sciences. In this project, the student will undertake a comparative analysis of two pathogen genome datasets: a dataset of 27 Escherichia coli and Shigella genomes, and a much larger dataset of 359 members of Staphylococcus aureus. Working in a Linux environment, the student will apply state-of-the-art and new computational methods to detect patterns of genetic exchange affecting members of each dataset, and/or delineate networks of genetic exchange of microbial communities. This project will offer hands-on experience in experimental design, data management, bioinformatic workflows, genome analysis, phylogenetics, network reconstruction and inference, advanced (high-performance) computing and scripting. The student will compare results in a sound statistical framework, and gain experience in the preparation of publication-quality reports and figures. On the biological side, the student will gain experience in genome biology and evolution of two important groups of bacterial pathogens. This project will be primarily informatic and computationally based, i.e. will not involve wet laboratory work. Project title: How Macrophages Eat Bacteria – Phagocytosis and Disease. Supervisor: Prof Jennifer Stow IMB Contact: j.stow@imb.uq.edu.au Macrophages do eat bacteria as a primary response in innate immunity. The process itself is ancient and vital for killing many pathogens and avoiding infection. Some human diseases (from tuberculosis to food poisoning) are caused by bacteria that pirate the phagocytic process to invade and colonize our cells. The regulation of phagocytosis at genetic, molecular and cellular levels and how this then relates to infectious and inflammatory diseases, is a major focus of our lab. We use genetic and molecular approaches and rely heavily on imaging cells and proteins as part of a national research program. Students are welcome to take on projects in this program. Discovery projects - aim to characterize GTPases as part of the cell trafficking and phagocytic machinery. Applied projects – assays for screening phagocytic proteins against peptide, drug and toxin libraries to find new antibacterial drugs.


Project title: Inflammation and Metabolism at the Tipping Point of Health and Disease. Supervisor: Prof Jennifer Stow IMB Contact: j.stow@imb.uq.edu.au Inflammation underlies many chronic diseases including, arthritis, cancer, inflammatory bowel disease, vascular disease, obesity and diabetes. Increasingly inflammation and immune cells are linked to control of metabolism. Our gut bacteria also play key, emerging roles in modulating inflammation and metabolism. This interplay is critical for understanding balances that maintain health and factors that promote disease – information needed as we head towards the era of personalized medicine. In several projects ongoing in the lab, we use genetic and molecular approaches and cell imaging to pinpoint macrophage genes that regulate cell signaling and activation in response to bacterial and metabolic cues. Work as part of a team unraveling human health and disease.


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