Centre for Population and Disease Genomics - Projects List
*Gender matters: Using genomic data to understand sex-specific risk in heart disease
Principal Advisor: Dr Sonia Shah (IMB)
Associate Advisor: Prof Gita Mishra (UQ School of Public Health)
The 2019 Women and Heart Disease forum highlighted clear disparities in CVD outcomes between males and females. The report (Arnott et al 2019 Heart, Lung and Circulation), highlighted a need to increase our understanding of sex-specific pathophysiology driving susceptibility to common diseases, and identification of sex-specific risk factors to improve early detection and prevention of CVD in women. Until recently, sex-specific research was underpowered and most studies on heart disease included a much smaller number of female participants. But this is beginning to change with the availability of large biobank data.
This project will require statistical analysis of very large datasets with health records linked to genomic data to address these gaps in our understanding of heart disease in women. This includes data from the UK Biobank cohort in ~500,000 individuals (54% women) and data from the Australian Women’s Longitudinal Study (led by Prof Gita Mishra), a study looking at the factors contributing to the health and wellbeing of over 57,000 Australian women, and is the largest, longest-running project of its kind ever conducted in Australia.
This project will lead to a better understanding of sex-specific risk factors for CVD, which will inform better CVD prevention strategies in women.
*Qualifies for the Global Challenges Scholarship.
*Genomics of Caveolae Disease
Principal Advisor: Dr Allan McRae (IMB)
Associate Advisor: Prof Robert Parton (IMB)
Caveolae, small pits in the plasma membrane, are the most abundant surface subdomains of many mammalian cells. Loss or mutation of genes involved in caveolae have shown to cause disease including lipodystrophy and pulmonary arterial hypertension. This project will ustilise publicly available genomic data to further explore the role of genetic variation in caveole genes in disease.
*Qualifies for the Global Challenges Scholarship.
*Harnessing biobank information to understand Motor Neuron Disease
Principal Advisor: Dr Allan McRae (IMB)
Associate Advisor: Dr Fleur Garton (IMB), A/Prof Robert Henderson (UQ Centre for Clinical Research)
Motor neuron disease results in the degeneration of the motor neurons leading to paralysis and death. There is limited knowledge on the underlying causes and no treatment can significantly change the fatal course of the disease. Slowing the discovery process has been the limited, clinic-based sample sizes. At least three large international biobank datasets, with matched genotype and phenotype data are now available and more are anticipated. The large sample provides a powerful opportunity to investigate this complex disease. Our group has expertise in harnessing large datasets such as the UK Biobank to answer questions about complex traits and diseases. This project will aim to integrate multiple international biobank datasets to better understand the disease and avenues for treatment.
*Qualifies for the Global Challenges Scholarship.
*Leveraging high-throughput genetic screens to evolve the power of algae in biotechnology
Principal Advisor: Prof Ben Hankamer
Associate Advisor: Prof Ian Henderson
Algae cells have evolved over ~3 billion years of natural selection to yield a diverse array of highly efficient, self-assembling, light-responsive membranes. These act as Nature’s solar interfaces, via which plants tap into the power of the sun. These interfaces contain nano-machinery to drive the photosynthetic light reactions which convert light from the sun into food, fuel, and atmospheric oxygen to support life on Earth. However, microalgae can be used to produce foods/nutraceuticals, vaccines, peptide therapeutics, novel antibiotics, fuel, and bioremediation. While much successful work has been done to improve the use of algae, the genetics of the various species are not well understood. Here we will deploy a high through put genetic approach to identify essential and conditionally-essential genes in algae providing insight into the fundamental biology of these organisms. We will leverage this approach to forcibly evolve algae and improve recombinant protein production.
*Qualifies for the Global Challenges Scholarship.
*Systems immunology and multi-omics approaches to understand protective immunity to human malaria
Principal Advisor: Prof Denise Doolan (IMB)
Associate Advisor: Dr Carla Proietti (IMB); Dr Jessica Mar (AIBN)
We invite applications for a PhD position focused on identifying human host factors that predict immune control of malaria. The project will utilise systems-based immunology and multi-omics approaches to profile the host immune response in controlled infection models of malaria at molecular, cellular, transcriptome and proteome-wide scale. The overall aim will be to develop and apply computational approaches, including network theory and machine learning, which integrate systems biology and molecular immunology to understand host-pathogen immunity and predict immune responsiveness and parasite control. Modelling of largescale existing datasets, including those generated by single cell RNA-sequencing technologies, may also be a feature of this project. The opportunity to identify new knowledge and integrate this with experimental data produced by our laboratory will be instrumental to extending the impact of these bioinformatics analyses. This project will provide an opportunity to be involved in cutting-edge advances integrating diverse fields of high dimensional omic datasets to inform the development of vaccines, immunotherapies or diagnostic biomarkers.
Methodologies: Bioinformatics, Machine Learning, Immunology, Systems Immunology, Systems Biology, Genomics/Proteomics/Transcriptomics, Molecular and Cell Biology, Statistics
Eligibility: Entry: BSc Honours Class I (or equivalent via outstanding record of professional or research achievements)
Experience/Background: Experience with programming languages, mathematics, statistics and/or background in immunology and molecular sciences, with an interest in integrating the fields of immunology and bioinformatics. Excellent computer, communication, and organisational skills are required. Forward thinking, innovation and creativity are encouraged.
*Qualifies for the Global Challenges Scholarship.
*Understanding the genetics of antibody dependent enhancement of disease
Principal Advisor: Dr Sonia Shah (IMB)
Associate Advisors: Dr Larisa Labzin (IMB), Dr Tim Wells (Frazer Institute); Prof Ian Henderson (IMB)
Antibodies are essential components of the adaptive immune system, which function in the clearance of infection and protection against reinfection. The role antibodies play in binding specifically to microbial antigens, neutralising their function, stimulating complement-dependent killing, and opsonization of the pathogen to promote clearance by macrophages and other immune cells, are well established. However, there is a growing appreciation that antibody can also drive disease pathology. Recent studies have demonstrated antibody-dependent enhancement (ADE) of bacterial infections resulting in more severe clinical outcomes. By stratifying patients with and without ADE, our group developed a treatment to treat multidrug resistant infections, successfully resolving life-threatening infections. While the molecular mechanisms of ADE of infection is beginning to be elucidated, why certain patients produce these deleterious antibodies remains unknown. Investigation of multiple cohorts of patients with differing infections reveal a consistent percentage of patients displaying ADE of disease suggesting a genetic basis for this phenomenon. Working with clinicians, molecular biologists and geneticists, this project seeks to determine if there is a genetic signature for ADE of bacterial infection.
*Qualifies for the Global Challenges Scholarship.