2021 Rising Star Award Recipients

Our genetic makeup (genotype) influences how we each individually look, as well as our disease risks (our genetic traits, or phenotype). But with more than three billion base pairs in human DNA, the exact links between genotype and phenotype are enormously complex.

This link is clear when the condition is caused by a single genetic variant (e.g Huntington’s Disease). However, many disease traits (e.g. diabetes, neurodegenerative diseases, mental health disorders) result from the combined effect of multiple genetic variants and also interaction with environmental factors. For these complex traits, identifying causal relationships between genotype and phenotype remains highly challenging.

Christina’s goal is to devise and apply statistical methods that will improve our ability to map associations between genotype and phenotype. Even after more than a decade of work in this field and growing genomic data repositories worldwide, we are still only able to explain about 11% of the variation in complex traits observed in humans.

“Without powerful and robust statistical methods, information hidden in the enormous volumes of biological data now being generated to study disease will go undiscovered,” says Christina.

Dr Christina Azodi uses cutting-edge genomic, statistical and data science approaches to uncover how genetic differences lead to differences in complex traits like disease susceptibility.

Christina joined SVI’s Bioinformatics & Cellular Genomics Laboratory in 2019, after formal training in computational biology during her PhD at Michigan State University and seven years of experience in functional genomics, data science, and machine learning.

Inherited blood disorders, caused by changes (mutations) in a person’s DNA, are only treatable by bone marrow transplantation. But for many affected children, a suitable donor is not available. For those who receive a transplant, the body’s rejection of donor cells can lead to life-threatening complications or failure of the treatment.

Astrid’s research takes a new approach to tackling inherited blood disorders: ‘editing’ the genetic code to repair ‘faulty’ DNA sequences, so as to restore normal function of a patient’s own bone marrow cells (meaning a donor is no longer needed).

“I have developed several new tools for DNA editing that this project will test in mice, so we can verify the tools’ effectiveness in a living animal. Using DNA editing to change the colour of a fluorescent marker, we will work to determine the best strategies for a safe and effective gene therapy for Australian patients,” says Astrid.

Dr Astrid Glaser is a gene editing expert driven to cure rare and debilitating diseases. Before joining SVI’s Genome Stability Laboratory in 2018, Astrid began her scientific training at the University of Vienna and completed her PhD at Murdoch Children’s Research Institute in Melbourne. Astrid’s expertise has been central to establishing gene editing technology at SVI, which is now used in many research projects.

Learn more about Astrid’s research in this short video.

More than one million Australians have type 2 diabetes. Many of these people will die from heart disease, and many more will have serious heart complications. Heart disease in these people is called diabetic heart disease, and there are currently no effective treatments.

Diabetic heart disease occurs because of high levels of glucose and fatty acids in the blood stream, which alter the heart’s energy metabolism. Healthy hearts use a mix of glucose and fatty acids to produce energy, while diabetic hearts rely almost entirely on fatty acids. As a result, diabetic hearts become larger, stiffer, and take longer to relax after each heartbeat.

This project will exploit a pre-clinical human heart organoid model developed in the Cardiac Regeneration Laboratory. This model, more simply known as a ‘heart in a dish’, is derived from human stem cells and contains functioning heart muscle cells, as well as blood vessels and neurons.

‘The beating heart tissues can mimic type 2 diabetes-induced heart disease when cultured in high levels of glucose and fatty acids,” says Jarmon. ‘We will use this to test new treatments in a human context.”

Dr Jarmon Lees uses his expertise in cardiovascular disease, stem cell biology and tissue engineering to deliver new therapeutic options for people faced with heart disease.

Jarmon joined the Cardiac Regeneration Laboratory in SVI’s O’Brien Department in 2018, after completing his PhD in neural cell metabolism at The University of Melbourne. His ‘heart in a dish’ is being used to model different types of heart disease and as a platform to speed up the development of new drugs.

Learn more about Jarmon’s research in this short video.

New imaging techniques that can ‘see’ at the level of individual cells in tissues promise enormous power for research and the future of medicine. But with this deep resolution comes massive amounts of data – the locations of millions of cells, along with valuable biological information about those cells’ form and function.

Such single-cell resolution imaging is likely to become more common in future, however, tools able to analyse the vast amounts of information generated are largely underdeveloped. This leaves experts severely underpowered in being able to extract quantifiable information from biomedical imaging data.

Cynthia will develop an open-source software tool that can identify and visualise cell clusters, infer cell-to-cell interactions, define the structure of each cell cluster and report the localisation of neighbouring cells. She will also publicly release a simple web-based, ‘click-and-go’ interactive tool for studying the patterns of cells in tissues – to support biologists with no knowledge of programming.

“The software and web-based tools will help biologists fully utilise their data, providing greater information from what is a largely untapped source of novel biological insight,” Cynthia says. “To date, very few tools have been produced to support the spatial analysis of cells in tissues.”

Cynthia’s work opens the way for SVI to develop imaging analysis expertise that can support researchers on the St Vincent’s campus and beyond.

Dr Cynthia Liu’s research is focused improving statistical analysis of large and complex biological datasets – to drive in new insights about the genetic basis of health and disease.

A postdoctoral researcher in SVI’s Bioinformatics & Cellular Genomics Laboratory, Cynthia completed her studies at The University of Melbourne, RMIT and The University of Adelaide. Cynthia is the author of 20 highly-cited publications.

Current cancer treatments often involve harsh chemotherapies that take a ‘sledgehammer’ approach to the tumour and as a result can have terrible side-effects. New targeted anti-cancer therapies, which cause cancer cells to die while sparing healthy cells, are sorely needed.

Michael has been applying an innovative approach to identify new drugs for the hardest-to-treat breast and ovarian cancers. This work has recently provided some intriguing hints about a particular metabolite that may be involved in controlling a cell’s ability to repair damage to its DNA. This is important because new therapies that treat breast and ovarian cancers specifically target DNA repair to kill cancer cells.

This project aims to explore the role of this metabolite in DNA repair.

“Further investigation into how this metabolite interacts with the DNA repair machinery may also inform targeted ways that diet could potentially be used to enhance current cancer treatments,” says Michael.

Dr Michael Sharp uses his in-depth knowledge of cellular DNA repair machinery and his technical expertise in the development of high-throughput assays to help identify new drugs for cancer.

Michael undertook his PhD in biochemistry and immunology at James Cook University, graduating in 2015. Prior to joining SVI in 2017, Michael worked as a scientist in the Microbiology and Allergens Laboratory at the National Measurement Institute.

Learn more about Michael’s research in this short video.

The bone marrow is a factory for making our blood, creating billions of blood cells every day. Distinct places (niches) within the marrow support the production of distinct blood cell lineages from stem cells.

Research points to regulation of these niches being key to balancing the different cell types (such as platelets) in the blood. However, the processes controlling this regulation are not known.

Slow blood cell recovery (particularly low platelet count) is common among bone marrow transplant recipients; typically one-third experience slow platelet recovery, which significantly increases their risk of acute bleeding, illness and death. Low blood cell counts can also persist for more than six months after cancer therapy, are life-threatening and are a major reason for delaying further cycles of treatment – significantly contributing to the failure of chemotherapy to control cancers.

Gavin’s project will for the first time apply innovative and advanced seven-colour microscopy imaging to identify niches in healthy mice and identify changes that occur following bone marrow transplant.

“My goal is to determine the relationship between the stem cells and the niche and how they are affected by bone marrow transplant,” says Gavin. “If we can do that, we are a step closer to understanding the factors that regulate these niches, and hence the regulation of blood cell production.”

Dr Gavin Tjin is an expert in light microscopy, a technique which uses visible light to detect tiny objects. Gavin’s passion is using microscopy techniques to solve biological questions – including how cells interact with their environment and how disease and treatment can alter these interactions.

Joining SVI’s Stem Cell Regulation Laboratory in 2017 as a postdoctoral researcher, Gavin has since independently established the institute’s innovative Opal multiplexing microscopy technique. Gavin completed his PhD at Sydney’s Woolcock Institute of Medical Research and is the author of 21 publications.

Type 2 diabetes is a massive health burden worldwide that can result in heart attack, stroke, blindness and amputation. Almost one million Australians have type 2 diabetes.

Influenced by genetic and family-related risk factors as well as environmental factors, the exact cause of the disease remains unknown.

Available treatments for type 2 diabetes do not adequately prevent disease progression – new treatments are therefore urgently needed.

Jessie’s research has identified a new potential means to address defects in the cells that produce insulin (beta cells) – defects that may be a key driver of type 2 diabetes progression.

“My work has identified a potential set of signalling molecules that can improve beta cell function,” says Jessie. “Inhibition of this pathway can stimulate higher insulin release, improve glucose tolerance, and may result in protective effects against diabetes-related stress on beta cells.”

The project will take Jessie’s initial findings to the next level, enabling further investigation of the pathway, alongside the development of testing to identify new potential drugs that act upon it.

Dr Jessie Yang’s research is focused on understanding underlying drivers in the body that lead to metabolic diseases (including diabetes and obesity), and how these processes can be harnessed to identify new treatments.

Following her PhD at The University of Melbourne, in 2019 Jessie joined SVI’s Diabetes & Metabolic Disease Laboratory to continue her promising research into type 2 diabetes.