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17 Nov 2020

Doherty Institute researchers awarded $3.9 million from ARC

Researchers from the Doherty Institute have received more than $3.9 million in the Australian Research Council (ARC) Discovery Project 2021 scheme, with eight significant projects supported through the funding.

Announced by the Minister for Education, the Hon. Dan Tehan, the Discovery Projects Scheme aims to fund innovative research that will benefit Australians.

University of Melbourne Professor Sammy Bedoui, a Laboratory Head at the Doherty Institute, has received $680,850 to unravel the complexities of cell death pathways, investigating the research question: why does the body have so many ways of killing its own cells?

“The body killing its own cells doesn’t intuitively feel like the right thing to do,” said Professor Bedoui.

“We know, however, that this feature has been preserved throughout evolution and is absolutely critical to the development of life.”

The aim of the project is to develop fresh insights in the area of programmed cell death, which could provide the knowledge base needed to improve our abilities to manipulate cell death in basic research and commercial applications.

Another project led by University of Melbourne Dr Nichollas Scott, a Laboratory Head at the Doherty Institute, has been awarded $534,500 to further research into protein glycosylation (the chemical addition of sugars to proteins), which is an important but poorly understood aspect of bacterial physiology.

“The goal of this project is to learn how bacteria use glycosylation to augment their proteomes, which could show us new ways to use bacterial glycosylation systems to create important glycoproteins - such as next generation vaccines,” said Dr Scott.

"Moving forward, insights into these systems could dramatically change how we produce commercially and medically important glycoproteins,” Dr Scott concluded.

ARC DP Recipients

Professor Sammy Bedoui - $680,850.00

Unravelling the complexities of cell death pathways. This project aims to test if cells can flexibly rewire their cell death pathways to ensure that the absence or inhibition of one type of cell death can be compensated through the triggering of another. The project expects to generate new knowledge in the area of programmed cell death, and more specifically will address why cells have multiple programmed ways to die. Expected outcomes of this project include the provision of unprecedented insights into the molecular regulation of how cells orchestrate and integrate cell death pathways. This should provide significant benefits, such as providing the knowledge base needed to improve our abilities to manipulate cell death both in basic research and commercial applications of cell death.

Dr Nichollas Scott - $534,500.00

Characterising O-linked glycosylation across Burkholderia. Protein glycosylation, the chemical addition of sugars to proteins, enables the augmentation of protein properties. Across the Burkholderia genus we have shown O-linked glycosylation is both conserved as well as essential for bacterial fitness. Yet, we have little understanding of how glycosylation modulates the proteome of this genus. This project aims to characterise the glycoproteomes of Burkholderia species and track the impact of glycosylation on both the proteome and protein stability. By understanding how glycosylation shapes the proteome we will gain a greater understanding of the role of bacterial glycosylation in Burkholderia physiology as well as how we may better utilise microbial glycosylation for glycoprotein production.

Professor Axel Kallies and Associate Professor Wei Shi - $520,363.00

Differentiation of effector and tissue regulatory T cells. Regulatory T cells (Tregs) populate almost every organ of the body and play a central role in preventing inflammation and maintaining health. To exercise these functions, Tregs undergo a developmental program, the details of which are poorly known. This project will utilize newly developed biological tools and state-of-the-art technology to uncover the molecular mechanisms that govern Treg development and function. The project will generate basic scientific knowledge and new intellectual property that will afford new opportunities for research and development. The outcomes of this project will help to devise strategies to treat diseases such as autoimmunity, cancer and metabolic syndrome, and will thus benefit veterinary and human health.

Professor Dale Godfrey and Dr Nicholas Gherardin - $489,715.00

CD1C-LIPID-REACTIVE T CELLS. The immune system patrols our body examining molecules such as proteins and lipids that signal whether or not everything is ok. While protein recognition by the immune system is well understood, our knowledge of the fundamental features of lipid detection is poor. This project will investigate the detection of lipid molecules that are presented to the immune system in association with a molecule known as CD1c. The aims are to understand: 1. The cells that respond to these lipids; 2. The cellular receptors that bind to these lipids; 3. The types of lipids involved in this process. This work is essential for us to understand lipid-based immunology which is critical if we ultimately wish to harness this to improve human health.

Dr Alexandra Corbett and Dr Zhenjun Chen - $434,588.00

Understanding the life and death of Mucosal-associated invariant T cells. Cell death of naïve T cells in lymphoid organs is well-understood. However, T cells only gain their function upon activation, and how activated T cells regulate their life or death remains unclear. Mucosal-associated Invariant T (MAIT) cells are abundant in non-lymphoid tissues as key local players in immunity, and share some features of activated conventional T cells. This project aims to define how MAIT cell survival and death are controlled. It combines methods we developed to track MAIT cells in vivo with expertise in cell death analysis. This project is expected to elucidate the complex mechanisms controlling MAIT cell survival/death and increase our fundamental understanding of cell death mechanisms of activated T cells.

Professor James McCaw, Dr Nicholas Geard and Dr Rebecca Chisholm - $390,000.00

Multiscale models in immuno-epidemiology. The spread of a pathogen (for example, a virus or bacteria) through a population is a multi-scale phenomena, influenced by factors acting at both the population and within-host scales. At the population scale, transmission is influenced by how infectious an infected host is. Infectiousness in turn depends on the balance between pathogen replication within the host and immune/drug control mechanisms. This project aims to develop new mathematical frameworks for simultaneously modelling these two scales. This will provide a platform for the rigorous study of complex biological interactions - such as the emergence and combat of drug-resistance - that shape society's ability to control infectious diseases in human, animal and plant systems.

Dr Simon Firestone, Dr Sebastian Duchene and Professor Jodie McVernon - $256,889.00

Nowcasting outbreaks leveraging genomic and epidemiological data. This project aims to inform outbreak response planning by developing new models of infectious disease outbreaks. The project expects to generate new knowledge on the processes driving ongoing outbreaks including those of the novel coronavirus (COVID-19) and African swine fever by integrating the latest advances in Bayesian outbreak inference alongside unique simulation approaches. Expected outcomes should include a shift in how models are developed and used to inform the response to outbreaks as they unfold. This should enable more rapid outbreak containment in Australia and overseas, leading to reduced impacts on public and animal health, and associated industries.

Professor Frank Caruso, Professor Stephen Kent, Dr Natalie Trevaskis, Dr Yi Ju, Dr Adam Wheatley and Professor Miles Davenport - $676,622.00

Impact of Biological Coatings on Nanoparticle–Immune Cell Interactions. Nanomaterials exposed to biological environments such as blood or lymph fluids rapidly adsorb a layer of biomolecules on their surface, forming a biomolecular corona, and profoundly altering their properties. This project aims to resolve the influence of biomolecular coronas on nanoparticle–immune cell interactions by combining particle engineering, immunology, proteomics and bioinformatic analysis. The project expected outcomes are to generate new knowledge in nanomaterial–immune cell behaviour and design principles for nanoparticles with prospective applications in the agricultural, veterinary and biomedical sectors.