Centre for Cell Biology of Chronic Diseases - Earmarked

Principal Advisor: Prof Alpha Yap (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.

This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.

This project aims to discover how epithelial tissues in the  body protect themselves against cell injury and cancerous transformation through the early detection and elimination of abnormal cells. Epithelia are found in major organs,  such as the lung, breast and gastrointestinal tract - tissues that are common sources of major diseases, such as inflammation and cancer. The Yap group has pioneered work to understand how mechanical forces are detected as early warnings of cellular dysfunction in epithelia. Conversely, we have found that abnormal tissue mechanics may increase the susceptibility of epithelial tissues to disease. We aim to understand how mechanical signals are detected, how they may be disturbed, and whether correcting mechanics can improve disease outcomes. We work at the interface between experimental biology and theoretical physics. So, projects can be tailored to student's interests, but will give experience in experimental cell biology and physical theory.

 *Qualifies for an Earmarked Scholarship.

Principal Advisor: Dr Benjamin Weger (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2026, which means you must apply no later than 30 September, 2025.

This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.

Non-alcoholic fatty liver disease (NAFLD) is a major global health problem and refers to a spectrum of liver conditions including simple steatosis, non-alcoholic steatohepatitis and fibrosis. NAFLD affects at least 25% of adults in developed nations and is a leading cause of cirrhosis and hepatocellular carcinoma, but current treatment options remain limited.

Increasing evidence points to a crucial role of gut microbiota in the pathophysiology of NAFLD, yet the underlying mechanisms remain scarcely understood. This PhD project is based on our findings that microbiota modulates growth hormone (GH) secretion of the host (microbiota-GH axis) to regulate diurnal/circadian liver physiology in a sex-dependent manner.

The study will explore the role of an altered microbiota-GH axis in NAFLD progression and will test whether its targeted modulation may provide a new way for treating NAFLD. This project involves a multi-omics approach and combines innovative cell culture and pre-clinical models of NAFLD. Students with an interest in liver physiology and/or the circadian clock are encouraged to apply.

 *Qualifies for an Earmarked Scholarship.

Principal Advisor: Professor Alpha Yap (IMB)

Associate Advisor: TBC

Two PhD projects are available as part of Professor Yap’s ARC Laureate Program which commences in 2024. This prestigious 5-year program aims to understand how cells communicate with one another by mechanical force to detect injury in epithelial tissues such as the gastrointestinal tract and embryonic skin. We apply physical and cell biological approaches to understand how those mechanical forces are generated and detected for tissue health and repair. We use innovative approaches from different disciplines, including live-cell microscopy and genetic manipulation in zebrafish embryos; experimental tools and theory from physics that provide new ways to understand the biological phenomena; and testing how failure of mechanical communication may allow injury to disrupt tissue integrity. Individual projects will be designed that emphasize different aspects within this overall program, tailored for the specific interests of students, which can range from biology to biological physics. Independent of the specific focus of an individual project, the interdisciplinary range of this Laureate Program provides an exciting opportunity for students to train across biological and physical disciplines, to enhance their capacity and versatility for the future.

Research Environment

These projects will be supported by the world-class resources of the IMB and the network of national and international experts who are collaborating with Professor Yap’s ARC Laureate Program. Depending on the specific requirements of each project, students have the opportunity to learn cutting-edge experimental approaches, such as biophysical techniques to analyse tissue mechanics and the use of organoids and zebrafish embryos to model cell injury and tissue responses. This project is part of a program that provide a rich, interdisciplinary network for their training. Local collaborators bring experience in cell biology (Prof. Rob Parton, Dr. Samantha Stehbens), zebrafish models (Dr Anne Lagendijk),inflammation (Professors Kate Schroder and Matt Sweet) and gastrointestinal function (Professor Jake Begun, MMRI-UQ); while national and international collaborators bring expertise in mechanobiology (e.g. Richard Morris, UNSW; Virgile Viasnoff, Nat Uni Singapore; Phillipe Marcq, ESPCI Paris). More broadly, the IMB and UQ campus provide a vibrant, multidisciplinary environment for this training, where they will get exposure to disciplines such as developmental biology, gastroenterology and genomics, as well as the cell biology and biophysics of the host lab.

*Qualifies for an Earmarked Scholarship.

Principal Advisor: Dr Anne Lagendijk (a.lagendijk@uq.edu.au)

Associate Advisor: Samantha Stehbens (AIBN/IMB; s.stehbens@uq.edu.au)

Cerebral Cavernous Malformation (CCM) is a progressive vascular disease whereby focal clones of defective endothelial cells give rise to distinctive bulging vascular lesions. The endothelial cells in progressed lesions show reduced adhesion with each other as well as cellular thinning and spreading. CCM lesions form exclusively in venous vessels of the central nervous system (CNS: brain and spinal cord), at a surprisingly high frequency of up to 0.5% of the population. Due to their location and fragile structure CCMs cause chronic headaches, seizures, and stroke. CCM disease is induced by mutations in one of three CCM genes: CCM1, CCM2, or CCM3 which leads to uncontrolled KLF2/4 transcription factor activity.

We recently identified novel factors that are downregulated in CCM disease, and when these factors are fully absent CCM phenotypes worsen. This project will investigate these new players using zebrafish and bioengineered 3D vessel-on-a-chip models and determine these might prevent CCM progression. 

 *Qualifies for an Earmarked Scholarship.

Principal Advisor: Prof Jennifer Stow (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.

This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.

Immune cells migrate through tissues to sites of infection or damage to provide immune defence and to promote tissue repair. Using advanced live cell imaging we can detect trails left by migrating immune cells that help guide other cells to sites of infection. This project will characterise this new form of signalling between cells, uncovering new aspects of immune cell migration vital for fighting  infection and wound healing. The project will build skills in cutting edge cell and tissue microscopy and imaging, including in model organisms and organoids, and involve biochemical and genetic analyses. The project is a collaboration between 3 universities with the potential for cross disciplinary research and training in a diverse team.

 *Qualifies for an Earmarked Scholarship.

Principal Advisor: Professor Ben Hankamer (b.hankamer@imb.uq.edu.au)

The global transition to reach Net Zero carbon dioxide emissions by 2050 is forecast to require US$144 trillion (or $5.5 trillion annually to 2050) of investment, highlighting an extraordinary opportunity to develop renewable technologies.

The sun is by far the largest renewable energy resource available to us, and every 2 hrs provides Earth with more energy than is required to power our entire global economy for a year.

Oxygenic photosynthetic organisms including plants, algae and cyanobacteria (and the intricate photosynthetic machinery within them) form the biological interface between the sun and our biosphere. Over 3 billion years, these intricate photosynthetic interfaces have evolved to capture this solar energy and CO2 to generate oxygen and biomass that provide the food, fuel, biomaterials, and clean water that support aerobic life on Earth.

The first step of photosynthesis and all light-driven biotechnologies is light capture by the Light Harvesting Complex (LHC) proteins associated with Photosystems I and II. This PhD project will focus on biochemically and functionally defining key LHC trimers and ~ 1MDa photosynthetic supercomplexes. This work supports the structure-guided design of next-generation high-efficiency CRISPR-engineered cell lines for light-driven biotechnology applications.

The successful PhD candidate will be part of a strong multi-disciplinary team in the Centre for Solar Biotechnology (CSB; 30 international teams, ~35 industry partners to date) within the Institute for Molecular Bioscience (IMB) at the University of Queensland (UQ). The IMB is one of Australia’s premier life sciences institutes and ranks highly internationally. UQ regularly ranks in the top 1% (top 50) universities internationally.

The CSB and our industry partners are focused on developing advanced light-driven biotechnologies based on single cell green algae that tap into this huge solar energy resource and use it to drive the production of a broad range of products from high-value recombinant proteins through to cost-competitive renewable fuels. The IMB has excellent protein biochemistry facilities (protein purification, cryo-electron microscopy and mass spectrometry) as well as powerful robotic systems (to screen for high-efficiency cell lines) to support this work.

The project will involve microalgal cell culture, light microscopy, purification of photosystem complexes by sucrose density gradient centrifugation and FPLC, biochemical and biophysical analyses of these complexes, negative stain and cryo-electron microscopy. They will also have the opportunity to use the state-of-the-art cryo-EM facilities to collect atomic resolution images for single particle analysis.

 *Qualifies for an Earmarked Scholarship.

Principal Advisor: Prof Jennifer Stow (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.

This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.

This student project is part of a grant-funded  industry partnership, with partners at UQ/IMB and Monash U/MIPS and an international pharmaceutical company.  As a student member of this team you will receive exceptional training and work experience at the interface between research in academic and industry settings. The project will be part of a broader program investigating how peptides and peptide drugs are absorbed across the wall of the gastrointestinal tract (GIT); multidisciplinary approaches are being taken by the team and the student project will be focussed on using multiple modes of microscopy to examine peptide uptake and distribution. Confocal microscopy, live imaging of cells, organoids, explants and tissues,  will be employed, using cutting edge equipment and state of the art technologies; there will be some biochemical  and protein studies and you will be involved in quantitative  image analysis and handling of big image data. Throughout the project you will work with world class experts for training, supervision and technical innovations. The project will be based at UQ (Brisbane) and involve active interstate and international collaborations. You will emerge from this project with translatable skills, work experience and scientific outputs, having contributed to a project that will have practical outcomes and global impact.

 *Qualifies for an Earmarked Scholarship.

Principal Advisor: Prof Alpha Yap (IMB)

This project requires candidates to commence no later than Research Quarter 1, 2024, which means you must apply no later than 30 September, 2023.

Chronic inflammation of epithelial organs, such as the gut, are known to predipose to cancer. But the mechanisms responsible for this predisposition are poorly understood. Elucidating such mechanisms are essential to identify patients at increased risk for cancer and present novel opportunities to decrease cancer risk.

This project builds on our pioneering discoveries to test how inflammation may increase cancer risk by altering the epithelium within which cancer originates. We recently made the exciting discovery that abnormalities in the mechanical properties of epithelial tissues may increase cancer risk by disabling the tissue's ability to eliminate newly-transformed cancer cells. Understanding how inflammation affects tissue mechanics will provide new opportunities for diagnosis and therapeutics.

This project will provide training in a wide range of modern research approaches, including advanced microscopy, bioengineered systems to study cell behaviour, and animal models of cancer development and elimination.

 *Qualifies for an Earmarked Scholarship.

Principal Advisor: Associate Professor Nathan Palpant (n.palpant@uq.edu.au)

Associate Advisors: Dr Sonia Shah (sonia.shah@imb.uq.edu.au) and Professor Mikael Boden (m.boden@uq.edu.au)

Genome sequencing is a powerful tool for studying the biological basis of disease, yet out of millions of data points, finding the underlying cause of disease can be difficult. Current protocols for classifying variants from patient DNA data largely rely on prior knowledge about normal and abnormal gene variation contained in large public databases, known disease-causing gene panels, or identifying variants causing amino acid changes in proteins (which only comprise 2% of the genome).

Despite these powerful approaches, studies indicate that classifying variants as pathogenic occurs in only a minority of cases and among variants reported in ClinVar, a public archive of relationships between human variation and phenotype, wherein a large proportion (37%) are classified as variants of unknown significance (VUS).

This project aims to address this key gap in knowledge, involving work in computational and/or cell biology studies, depending on the student skills and interests. For computational studies, this project aims to develop methods that integrate predictive, genome-wide identifiers of pathogenicity. We will use machine learning to build non-linear prediction methods that outperform individual prediction tools in identifying genetic causes of disease and accelerating clinical diagnosis of genetic diseases. For cell biology studies, we aim to use clinical genetics data (from the Australian Functional Genomics Network) to determine pathogenicity of variants from patients with inherited cardiovascular diseases.

The approaches will include: 1) cell modelling with human pluripotent stem cells (hPSCs), a disease-agnostic and scalable platform for high-throughput hPSC variant screening. To study variants in genes such as transcription factors that are known to cause genetic diseases, we will use molecular phenotyping by genome-wide proximity labelling with DNA adenine methyltransferase (DamID) to study how disease-causing variants alter regulatory control of the genome. Collectively, this aim implements computational predictions with disease modelling as an efficient, scalable, and disease agnostic pipeline to increase the diagnostic rate of unresolved cases.

*Qualifies for an Earmarked Scholarship.

Principal Advisor: Prof Alpha Yap (a.yap@uq.edu.au)

Two PhD projects are available as part of Professor Yap’s ARC Laureate Program which commences in 2024. This prestigious 5-year program aims to understand how cells communicate with one another to detect injury in epithelial tissues such as the gastrointestinal tract and embryonic skin.

We propose that a key factor lies in how cells use mechanical forces to communicate with each other. We apply physical and cell biological approaches to understand how those mechanical forces are generated and detected for tissue health and repair. We use innovative approaches from different disciplines, including live-cell microscopy and genetic manipulation in zebrafish embryos; experimental tools and theory from physics that provide new ways to understand the biological phenomena; and testing how failure of mechanical communication may allow injury to disrupt tissue health through inflammation and infection.

Individual projects will be designed that emphasize different aspects within this overall program, tailored for the specific interests of students, which can range from biology to biological physics. Independent of the specific focus of an individual project, the interdisciplinary range of this Laureate Program provides an exciting opportunity for students to train across biological and physical disciplines, to enhance their capacity and versatility for the future.

 *Qualifies for an Earmarked Scholarship.