06 Nov 2023
Discovery Research projects granted $4.4 million in funding from Australia Research Council
Successful in the Australian Research Council (ARC) Discovery Projects Scheme, researchers at the Doherty Institute have been awarded a combined total of $4.4m for research projects investigating a range of topics from longevity of immunity and T cell death mechanisms, to how bacteria feel and effective pandemic response.
The Discovery Projects Scheme supports excellence in basic and applied research and funds projects that will advance knowledge and foster innovation, while expanding research capability in Australia.
University of Melbourne Laureate Professor Sharon Lewin, Director of the Doherty Institute, congratulated the grant recipients for their success.
“I am proud to see many of our researchers and their work recognised by the Australian Research Council. These prestigious grants are highly competitive and are a testament to the quality and potential of our colleagues’ research to make significant contributions to our understanding of important issues in infection and immunity,” said Professor Lewin.
Seven projects involving Doherty Institute researchers have successfully secured funding with ARC Discovery Project Grants. Find out more about each research project below.
This project will investigate the cellular and molecular pathways regulating lifespan of tissue-resident memory T cells (Trm cells), a non-circulating T cell subset that play a crucial role in the frontline defense against infection. Significantly, how long Trm cells live is paramount to how long immunity is sustained. Using cutting-edge cellular and molecular techniques, the expected outcomes of this project include identification of the genes and processes that control lifespan. This should provide significant benefits in the basic knowledge of how longevity of immunity is regulated. This understanding will be useful for future immunotherapeutic applications, such as veterinary or human vaccines requiring maximal duration of immunity.
Professor Katherine Kedzierska (Doherty Institute)
Science generally studies antigenic stimulation in isolation, by measuring immunity towards antigens derived from a single pathogen. However, as mammals can harbour more than one infection at any given time, we established a model of antigenic interference using different antigens derived from two unrelated pathogens, influenza A (IAV) and Semliki Forest virus (SFV). Our data show that prior exposure to either IAV or SFV greatly perturbs T cell dynamics. This proposal will study, at cellular and molecular levels, T cell trafficking, function and clonal distribution during antigenic interference, thus advance fundamental knowledge on T cell immunity during antigenic competition, and provide a new paradigm on how we research T cell immunity.
Mammalian cells die via several different mechanisms, each of which is tightly controlled at a molecular level. The choice of death pathway depends on the trigger and cell type. This project will investigate the mechanisms controlling death of T cells, including conventional T cells, and unconventional T cells, such as mucosal-associated invariant T (MAIT) cells, in normal conditions and during inflammation. It combines methods we developed to study MAIT cells in vivo with expertise in cell death analysis. This project is expected to elucidate the complex mechanisms controlling T cell survival and death and increase our fundamental understanding of cell death mechanisms of activated T cells.
This project aims to investigate how newly discovered immune cells, known as 'MR1T' cells, function in the body. Preliminary evidence shows that MR1T cells can kill stressed cells. This project expects to generate new knowledge describing precisely how MR1T cells target and kill stressed cells. Expected outcomes of this project include to refine research techniques and models, foster interinstitutional collaborations, and further develop our theory on MR1T cell function. This project should provide significant benefits, such as publication of research articles in high impact journals and generation of experimental tools sought after by researchers in the field.
Bacteria have feelings. They sense and respond to changes using proteins called ‘two-component signalling systems’ (TCSS). These comprise a sensor which activates a DNA binding protein in response to specific cues (signals). Using state-of-the-art genetic techniques and a synthetic biology approach, this research aims to reveal for the first time how these complex bacterial TCSS networks interact. The outcomes will be a fundamental, new understanding of how bacteria sense and respond to environmental signals; a deep dive into how bacteria feel. This knowledge will be the basis for innovative approaches to harness bacteria in biotech such as vaccine production, biofuels or clever therapeutic interventions to stop bacterial infections.
The adaptive immune system consists of a complex cellular network that can efficiently distinguish exogenous required inputs, such as nutrients, from those that are potentially harmful like pathogens. Such ‘friend-foe’ discrimination has its molecular basis in a multitude of receptors with specificity to certain ligands. Critically, however, it is unclear how such discrimination is mechanistically regulated at the functional level. We have developed new and sophisticated experimental models that will allow us to systematically dissect and unfold the complexity of the adaptive immune system and address this critical knowledge gap. Expected outcomes will critically advance our general understanding of a fundamental biological principle.
Dr Freya Shearer (University of Melbourne), Professor James McCaw (University of Melbourne), Professor Nicholas Golding (Telethon Kids Institute), Dr David Price (Doherty Institute) and Dr Gerard Ryan (University of Melbourne)
COVID-19 has demonstrated the critical role of epidemic data and analytics in guiding government response to pandemic threats, reducing disease and saving lives. The demand for epidemic analytics for response to threats of national significance will only grow. The goals of this project are to 1) determine the combination(s) of surveillance methods that provide the most useful data for epidemic analysis, and 2) translate these findings into the blueprint for a next-generation infectious disease surveillance system for Australia. We will use a simulation-evaluation approach, coupling methods from infectious disease modelling with those from information theory optimal design. Outcomes will enable more tailored and effective pandemic response.
For more information on the ARC Discovery Projects Grant Scheme, visit https://www.arc.gov.au/funding-research/discovery-linkage/discovery-program/discovery-projects