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The lipidomics of cell fate. This project aims to dissect the roles of lipids in cell fate. The study of lipids, or lipidomics, is an emerging and exciting area of biological science. The fundamental roles of lipids in development remain vastly understudied. This project will look at reprogramming of somatic cells into stem cells, their pluripotency and differentiation. This will be complemented with studies in the zebrafish, which permits the direct study of cell fate in vivo. This approach is ....The lipidomics of cell fate. This project aims to dissect the roles of lipids in cell fate. The study of lipids, or lipidomics, is an emerging and exciting area of biological science. The fundamental roles of lipids in development remain vastly understudied. This project will look at reprogramming of somatic cells into stem cells, their pluripotency and differentiation. This will be complemented with studies in the zebrafish, which permits the direct study of cell fate in vivo. This approach is a powerful way to unlock major events involved in development and to unmask the roles of lipids in these fundamental mechanisms.Read moreRead less
Targeting mitochondrial dysfunction in disease. Defects in mitochondria, the energy producing compartments within cells, lead to severe neurodegenerative diseases and contribute to the development of cancer. Treatment for such diseases caused by mutations in mitochondrial DNA remains unsatisfactory and mostly confined to supportive measures. The identification of proteins that regulate gene expression within mitochondria provides an unexplored resource of potential disease modulators and drug ta ....Targeting mitochondrial dysfunction in disease. Defects in mitochondria, the energy producing compartments within cells, lead to severe neurodegenerative diseases and contribute to the development of cancer. Treatment for such diseases caused by mutations in mitochondrial DNA remains unsatisfactory and mostly confined to supportive measures. The identification of proteins that regulate gene expression within mitochondria provides an unexplored resource of potential disease modulators and drug targets. This research will lead to new strategies in the design of improved anticancer drugs, which is an important Australian research priority that will promote and maintain good health, and provide potential commercial outcomes.Read moreRead less
Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specifi ....Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specific key genes deregulated in cancer, to correct their expression and stably reprogram the phenotype of the tumour cell in a normal-like state. It outlines the engineering of novel synthetic agents to block specific protein-protein interactions in cancer cells and to induce potent tumour cell death. This work will generate novel and selective therapeutics to treat un-curable forms of tumours.Read moreRead less
The regulation of skeletal muscle mass. This project aims to delineate a pathway involved in regulating skeletal muscle mass, and examine whether disrupting mitochondrial phospholipid synthesis affects mitochondrial structure and function, causing muscle wasting. Defining a new atrophy pathway will advance understanding of the mechanisms that control muscle mass. This project could have important economic and quality of life benefits, especially for agriculture, where achieving optimal muscle ma ....The regulation of skeletal muscle mass. This project aims to delineate a pathway involved in regulating skeletal muscle mass, and examine whether disrupting mitochondrial phospholipid synthesis affects mitochondrial structure and function, causing muscle wasting. Defining a new atrophy pathway will advance understanding of the mechanisms that control muscle mass. This project could have important economic and quality of life benefits, especially for agriculture, where achieving optimal muscle mass ensures international competitiveness, productivity and economic growth, and successful ageing, where maintaining muscle mass is essential.Read moreRead less
Determining how calcium regulates mitochondrial function in models of cardiomyopathy. Heart failure is the leading cause of death in Australia. This project will determine the mechanisms by which the failing heart is associated with disorganisation of the cell and poor energy supply so that interventions aimed at reducing the development of heart failure can be developed.
Regulation and role of metabolic networks for respiration in plants. This project aims to understand the regulation of respiration in plants which underpins the energy provision that cells need to operate. Understanding respiration and how it responds to the changing environment is a building block needed for rational engineering of our future food from plants.
Characterizing the regulators of mitochondrial biogenesis in Arabidopsis thaliana. The overall aim of this project is to identify and characterise the underlying regulatory factors that control mitochondrial mass and number in plants. The project will exploit a regulatory mechanism that links the mitochondrial import machinery and the respiratory chain. Utilising both forward and reverse genetic approaches, the abundances of protein import translocases will be altered and the changes to mitochon ....Characterizing the regulators of mitochondrial biogenesis in Arabidopsis thaliana. The overall aim of this project is to identify and characterise the underlying regulatory factors that control mitochondrial mass and number in plants. The project will exploit a regulatory mechanism that links the mitochondrial import machinery and the respiratory chain. Utilising both forward and reverse genetic approaches, the abundances of protein import translocases will be altered and the changes to mitochondrial biogenesis will be investigated. This will identify regulatory factors, which can be manipulated and used to alter mitochondrial number and activity.Read moreRead less
Deciphering the Thermal Acclimation of Mitochondrial Respiration. Plants acclimate to the extremes of temperature following a pre-exposure to a sub-lethal increase/decrease in temperature. Recent research has revealed that proteins of oxidative phosphorylation and the tricarboxylic acid (TCA) cycle are dynamic and change their abundance in response to temperature change. Harnessing a cutting edge protein mass spectrometry approach, this project seeks to better understand how mitochondrial respir ....Deciphering the Thermal Acclimation of Mitochondrial Respiration. Plants acclimate to the extremes of temperature following a pre-exposure to a sub-lethal increase/decrease in temperature. Recent research has revealed that proteins of oxidative phosphorylation and the tricarboxylic acid (TCA) cycle are dynamic and change their abundance in response to temperature change. Harnessing a cutting edge protein mass spectrometry approach, this project seeks to better understand how mitochondrial respiration and hence adenosine triphosphate (ATP) production is maintained during temperature change. Uniquely this project will examine this in both the model plant Arabidopsis and wheat and combine both tissue, environment-induced and genotype variation to reveal a new understanding of the thermal acclimation of this major mitochondrial process.Read moreRead less
Unlocking secrets of fertility restoration for hybrid breeding in crops. Hybrid varieties give higher and more stable yields than conventional lines, but a cost-effective system to make hybrid seed on a commercial scale is still missing for economically important crops like wheat or barley. By elucidating the mode of action of a new type of restorer gene plus exploiting ancient or exotic wheat and barley collections this project will reveal aspects of largely understudied mechanisms underlying f ....Unlocking secrets of fertility restoration for hybrid breeding in crops. Hybrid varieties give higher and more stable yields than conventional lines, but a cost-effective system to make hybrid seed on a commercial scale is still missing for economically important crops like wheat or barley. By elucidating the mode of action of a new type of restorer gene plus exploiting ancient or exotic wheat and barley collections this project will reveal aspects of largely understudied mechanisms underlying fertility restoration in wheat and barley. The expected outcomes of the proposed research have the potential to deliver new tools for hybrid seed production programs in wheat and barley. Higher and more stable yields from hybrids will ensure food security in the face of an uncertain climate and growing human population.Read moreRead less
Establishing Vibrio natriegens as Ultra-Rapid Host for Synthetic Biology. This project aims to harness Vibrio natriegens, the world’s fastest-growing bacterium, as a microbial cell factory for synthetic biology and biotechnology. The project expects to develop new genetic tools and genetically-engineered microbes that can rapidly transform cheap feedstocks, such as plastic waste, into valuable chemicals and bioplastics. Expected outcomes include new knowledge on the mechanisms driving V. natrieg ....Establishing Vibrio natriegens as Ultra-Rapid Host for Synthetic Biology. This project aims to harness Vibrio natriegens, the world’s fastest-growing bacterium, as a microbial cell factory for synthetic biology and biotechnology. The project expects to develop new genetic tools and genetically-engineered microbes that can rapidly transform cheap feedstocks, such as plastic waste, into valuable chemicals and bioplastics. Expected outcomes include new knowledge on the mechanisms driving V. natriegens’ rapid growth, as well as building Australian multidisciplinary research capacity in synthetic biology that can translate this potential into bio-manufacturing processes. Significant benefits include the means to cut plastic pollution in our environment and to provide the basis for a carbon-negative chemical industry.Read moreRead less