Characterising the lipid droplet-mitochondria proteome. This project aims to determine the mechanisms by which the mitochondria and lipid droplets associate, and how this interaction influences lipid metabolism. Both critical for survival, lipid droplets are the bulk energy store in cells and the mitochondria break down this lipid to generate energy. It is anticipated that this project will identify the proteins that are critical for regulating contact between these organelles and the consequenc ....Characterising the lipid droplet-mitochondria proteome. This project aims to determine the mechanisms by which the mitochondria and lipid droplets associate, and how this interaction influences lipid metabolism. Both critical for survival, lipid droplets are the bulk energy store in cells and the mitochondria break down this lipid to generate energy. It is anticipated that this project will identify the proteins that are critical for regulating contact between these organelles and the consequences if this process becomes dysregulated. The project expects to provide fundamental new knowledge in understanding how organelles interact and how lipid metabolism is regulated. This knowledge has applications for the primary industries and biotechnology sector.Read moreRead less
Development of technologies to monitor multimolecular complexes. Development of technologies to monitor multimolecular complexes. This project aims to develop technologies to monitor how proteins and their interacting molecules (such as hormones) form multi-component complexes, and how these complexes function in the cell, including movement from the cell surface, into different cellular compartments and back up to the surface. These technologies are expected to enable monitoring in live cells i ....Development of technologies to monitor multimolecular complexes. Development of technologies to monitor multimolecular complexes. This project aims to develop technologies to monitor how proteins and their interacting molecules (such as hormones) form multi-component complexes, and how these complexes function in the cell, including movement from the cell surface, into different cellular compartments and back up to the surface. These technologies are expected to enable monitoring in live cells in real-time with high sensitivity. This project could have broad benefits for and affect study of all aspects of the life sciences at the cellular and molecular levels. How these protein complexes function in cells underpins much of our understanding of biology, and technological tools.Read moreRead less
The molecular blue-print for a mitochondrial nanomachine. The objective of the project is to develop a comprehensive understanding of the architecture of a biological nanomachine through broad-reaching investigation of the molecular contacts that enable the component parts to work together. The project plans to take the foundation knowledge of each of the component parts and build a conceptual framework of engineering principles to understand how the nanomachine is assembled, using a breakthroug ....The molecular blue-print for a mitochondrial nanomachine. The objective of the project is to develop a comprehensive understanding of the architecture of a biological nanomachine through broad-reaching investigation of the molecular contacts that enable the component parts to work together. The project plans to take the foundation knowledge of each of the component parts and build a conceptual framework of engineering principles to understand how the nanomachine is assembled, using a breakthrough technology to address the precise architecture of the component parts within the nanomachine.Read moreRead less
Molecular insights into bacterial metal ion homeostasis and toxicity. This project aims to measure bacterial cellular metal concentrations, elucidate mechanisms cells use to adapt to changing extracellular metal concentrations, and reveal the molecular targets of metal toxicity. Metal ions are essential to all forms of life, and half of all proteins use metal ions for cellular chemical processes. However, how cells precisely balance sufficient metal ions for essential cellular chemistry without ....Molecular insights into bacterial metal ion homeostasis and toxicity. This project aims to measure bacterial cellular metal concentrations, elucidate mechanisms cells use to adapt to changing extracellular metal concentrations, and reveal the molecular targets of metal toxicity. Metal ions are essential to all forms of life, and half of all proteins use metal ions for cellular chemical processes. However, how cells precisely balance sufficient metal ions for essential cellular chemistry without accumulating a toxic excess (metal homeostasis) is poorly understood. Discovering the roles of metal ions in bacterial cells will be key to defining the chemical biology of living systems and will provide information essential to understanding how microbes adapt to changing environments.Read moreRead less
New molecular tools to study the mechanisms of bacterial metal homeostasis. This project aims to provide new insight into how metal ion uptake is regulated. It will precisely measure the cellular concentrations of metal ions, reveal the roles of metal ions in essential cellular processes, and identify the molecular targets of metal toxicity. Metal ions are essential to all forms of life and are used by up to half of all proteins to facilitate cellular chemical processes. The intended outcome of ....New molecular tools to study the mechanisms of bacterial metal homeostasis. This project aims to provide new insight into how metal ion uptake is regulated. It will precisely measure the cellular concentrations of metal ions, reveal the roles of metal ions in essential cellular processes, and identify the molecular targets of metal toxicity. Metal ions are essential to all forms of life and are used by up to half of all proteins to facilitate cellular chemical processes. The intended outcome of the research is to provide new fundamental knowledge of the roles of metal ions in bacterial cells; knowledge that will be key to defining the chemical biology of living systems and will provide information essential to understanding how microbes adapt to changing environments.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE150101196
Funder
Australian Research Council
Funding Amount
$403,536.00
Summary
Elucidation and characterisation of the misfolded protein interactome. Correct expression, folding, and clearance of proteins are critical for all cell functions. However, cell stresses and aging can cause protein balance mechanisms to become overloaded, resulting in the misfolding and aggregation of proteins. Understanding the mechanisms by which protein aggregation occurs and how to prevent the process have become major scientific challenges. This project aims to gain unprecedented insights in ....Elucidation and characterisation of the misfolded protein interactome. Correct expression, folding, and clearance of proteins are critical for all cell functions. However, cell stresses and aging can cause protein balance mechanisms to become overloaded, resulting in the misfolding and aggregation of proteins. Understanding the mechanisms by which protein aggregation occurs and how to prevent the process have become major scientific challenges. This project aims to gain unprecedented insights into the interactors, effectors and fate of misfolded protein aggregates within cells, using new, cutting-edge, catalytic-tagging biochemical tools. Critical interactions will be investigated for their roles in protein aggregation cell death, and in whether modulation of the interaction can also mitigate or reverse the process.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 combined use of proteomics and small molecules for target identification and pathway analysis. This project intends to investigate how a series of new small molecules identified from our research to improve the metabolic effects of insulin. This project will integrate medicinal chemistry with proteomics and metabolic biology to identify the cellular targets and their mechanism of action.
Development and use of novel technologies to improve drugs targeting G protein-coupled receptor complexes involved in disease. The purpose of this project is to develop and use new and innovative technologies to improve many of the drugs taken for a wide range of medical conditions. The expected outcomes are the discovery of better drugs and a greater understanding of the drugs currently on the market, particularly enabling improved management of side-effects.
Discovery Early Career Researcher Award - Grant ID: DE120102556
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
The influence of crosstalk between protein post-translational modifications on the propagation of molecular signals. The ability of a cell to respond appropriately to its surroundings is a result of interactions between proteins and chemical modifiers termed post-translational modifications (PTM). This project will show how PTM interactions (competition/ cooperation) influence cellular outcomes in response to changes in the environment.