Is FGF21 the master regulator of protein intake? The project plans to bring together two major, rapidly growing disciplines – nutritional geometry and metabolic signalling – to address a topic of fundamental biological significance: the regulation of protein intake. A specific capacity to regulate protein intake has been shown for organisms spanning slime moulds to humans, yet the controlling mechanisms remain elusive. The project aims to test the hypothesis that fibroblast growth factor 21, rel ....Is FGF21 the master regulator of protein intake? The project plans to bring together two major, rapidly growing disciplines – nutritional geometry and metabolic signalling – to address a topic of fundamental biological significance: the regulation of protein intake. A specific capacity to regulate protein intake has been shown for organisms spanning slime moulds to humans, yet the controlling mechanisms remain elusive. The project aims to test the hypothesis that fibroblast growth factor 21, released from the liver under low protein nutrition, is a master regulator of protein intake. Understanding the mechanisms of protein appetite may have implications for organismal biology, understanding social interactions, the structure of food webs and the health and welfare of food and companion animals and humans.Read moreRead less
A molecular structure-function investigation of major membrane channels involved in olfactory transduction. Olfactory receptor neurons are extraordinarily-sensitive sensors for detecting minute concentrations of odorant molecules. This project aims to extend our previous studies of these specialised mammalian olfactory cells by using state-of-the art technologies: electrophysiology (patch-clamp) and molecular biology (site-directed-mutagenesis), to investigate how the molecular structure of the ....A molecular structure-function investigation of major membrane channels involved in olfactory transduction. Olfactory receptor neurons are extraordinarily-sensitive sensors for detecting minute concentrations of odorant molecules. This project aims to extend our previous studies of these specialised mammalian olfactory cells by using state-of-the art technologies: electrophysiology (patch-clamp) and molecular biology (site-directed-mutagenesis), to investigate how the molecular structure of their ion channels (selective protein pores) and receptors contribute to the odorant-induced generation of electrical activity, which mediates our sense of smell (olfaction). The project has specific relevance for understanding olfaction, as well as relevance for other sensory systems and other ion channels.Read moreRead less
Next generation high throughput lipidomics using adaptive modelling. This project aims to develop a unique high-throughput method to capture the lipidomic profile of human plasma suitable for large human population screening. Lipids are fundamental to every biological system, but our understanding of their regulation in humans have been largely superficial. By incorporating a new lipidomics approach, with genomic data, this project aims to expand our understanding of human biology by identifying ....Next generation high throughput lipidomics using adaptive modelling. This project aims to develop a unique high-throughput method to capture the lipidomic profile of human plasma suitable for large human population screening. Lipids are fundamental to every biological system, but our understanding of their regulation in humans have been largely superficial. By incorporating a new lipidomics approach, with genomic data, this project aims to expand our understanding of human biology by identifying regulators of lipid metabolism. The large diversity in humans necessitate sufficient sample sizes to identify true genetic regulators, but to date techniques capturing phenotypic data (lipids) have been largely limited. It is anticipated that this study will identify new regulators of lipid metabolism in humans.Read moreRead less
Commensal benefits: genomic basis for suppressing plant pathogens with Pseudomonas biocontrol species. Food security is an issue of mounting significance due to unpredictable climate trends and increasing global population growth. A feature of paramount importance to reliable crop production is the capacity to control plant diseases. This project investigates natural plant colonising bacteria as a tool for protecting plants from disease.
High-resolution multiscale modelling of pandemics: COVID-19 and beyond. The project aims to develop high-resolution computational models for pandemic mitigation and control, focussing on the novel coronavirus and its emerging variants, and leveraging demographic, genomic and epidemiological data. It expects to rigorously compare multi-scale effects of complex vaccination and social distancing strategies and quantify optimal responses under the COVID-19 induced uncertainty. The intended outcomes ....High-resolution multiscale modelling of pandemics: COVID-19 and beyond. The project aims to develop high-resolution computational models for pandemic mitigation and control, focussing on the novel coronavirus and its emerging variants, and leveraging demographic, genomic and epidemiological data. It expects to rigorously compare multi-scale effects of complex vaccination and social distancing strategies and quantify optimal responses under the COVID-19 induced uncertainty. The intended outcomes include computational models of how the most infectious viral variants emerge and spread in presence of interventions, how to predict the outbreaks, and which are the most vulnerable communities. This should make a significant economic and social impact, improving population health while maintaining a resilient economy.Read moreRead less
Using venoms to map critical and evolutionary conserved vulnerabilities. We have developed and applied new functional genomic approaches to study venom evolution. Using CRISPR screening, we find that unrelated venoms act on cells by exploiting the same vulnerabilities. By functionally mapping these vulnerabilities for all venom classes, we can begin to develop universal venom antidotes. Conversely, much of what we know about venom mechanisms comes from a small percentage of the biodiversity with ....Using venoms to map critical and evolutionary conserved vulnerabilities. We have developed and applied new functional genomic approaches to study venom evolution. Using CRISPR screening, we find that unrelated venoms act on cells by exploiting the same vulnerabilities. By functionally mapping these vulnerabilities for all venom classes, we can begin to develop universal venom antidotes. Conversely, much of what we know about venom mechanisms comes from a small percentage of the biodiversity within a venom, and we have developed genomic tools to study the venom “dark matter”. This work will lead to the full molecular characterisation of venom biodiversity, and new venom components will be useful for research or as novel medicines.Read moreRead less
Decision-making modules in protein interaction networks. This project aims to discover how cells use proteins to make decisions. This is important for all living things, which must react to stimuli to grow, adapt, defend themselves and to die. The project’s anticipated outcome is the systems-level identification of decision-making modules in an intracellular network. Its focus is on the smallest possible modules, which contain a decision-making protein with two modifications that control protein ....Decision-making modules in protein interaction networks. This project aims to discover how cells use proteins to make decisions. This is important for all living things, which must react to stimuli to grow, adapt, defend themselves and to die. The project’s anticipated outcome is the systems-level identification of decision-making modules in an intracellular network. Its focus is on the smallest possible modules, which contain a decision-making protein with two modifications that control protein-proteins interactions. It will investigate two recurrent decision-making modules. The expected benefits of the project include new means to decipher biological complexity, and targets to modulate biosystems by genome editing or with drugs.Read moreRead less
The role and regulation of protein methylation: a study using the recently developed methylation network of yeast. Tiny changes to proteins, such as methylation, can alter the way they interact with other proteins. This project will investigate the dynamics of protein methylation during the life of the yeast cell. The project results will be of long term relevance to situations where we may want to stop cells dividing, such as cancer or infectious disease.
The effect of methylation and phosphorylation on ribosome function. This project aims to discover how cells regulate ribosome function and selectivity, by modifying their ribosomal proteins. This affects protein synthesis, a process which is central to the growth of all living things. Expected outcomes include new knowledge on the regulation of protein synthesis, improved techniques for the study of this process and an enhanced capacity for international collaboration. New avenues for the artifi ....The effect of methylation and phosphorylation on ribosome function. This project aims to discover how cells regulate ribosome function and selectivity, by modifying their ribosomal proteins. This affects protein synthesis, a process which is central to the growth of all living things. Expected outcomes include new knowledge on the regulation of protein synthesis, improved techniques for the study of this process and an enhanced capacity for international collaboration. New avenues for the artificial regulation of the ribosome may also emerge, relevant to synthetic biology and the engineering of industrial yeasts. The project should provide significant new findings for the research community, generate research citations and contribute to a highly skilled workforce by the training of staff and students.Read moreRead less
Inflammation as an early form of maternal-fetal signalling in pregnancy. The project aims to understand the role of inflammatory signalling in marsupial pregnancy. This project is expected to explain why inflammation, a processes normally confined to injury and infection, is a part of reproduction in live-bearing mammals. Outcomes of this project include robust measures of the capacity for, impact of, and evolution of, inflammatory signalling in marsupial pregnancy. The project will provide new ....Inflammation as an early form of maternal-fetal signalling in pregnancy. The project aims to understand the role of inflammatory signalling in marsupial pregnancy. This project is expected to explain why inflammation, a processes normally confined to injury and infection, is a part of reproduction in live-bearing mammals. Outcomes of this project include robust measures of the capacity for, impact of, and evolution of, inflammatory signalling in marsupial pregnancy. The project will provide new knowledge about the unique biology of Australia's marsupial fauna.This project will provide significant benefits, including enhanced capacity for reproduction research in Australia, new international collaborations between Melbourne and Yale, and a new explanation for the puzzling role of inflammation in pregnancy.Read moreRead less