MicroRNAs are a group of molecules that are critical for controlling the activity of genes. They function in a diverse range of biological systems, from early embryonic development to adult organs, such as the brain and immune system. Although we know that these molecules are important, there remain major gaps in our understanding of how they are produced. Thus, the goal of our research is to understand how cells make these molecules.
The role of the protease inhibitor Serpinb9 in antigen cross-presentation by dendritic cells. This project will provide fundamental new insights into antigen cross-presentation, a crucial facet of the immune system's response to viral infection or neoplastic cells. It will also provide a basis for future studies into mechanisms of immune tolerance and enhance our understanding of autoimmune disease.
Characterisation of a powerful molecular motor, the FtsK DNA translocase. The FtsK protein is a fast and powerful molecular motor, a pump that can, and does, move an entire bacterial chromosome. This project will uncover the detail of the mechanism used by this motor to convert the cell's chemical energy source Adenosine Triphosphate (ATP) into movement of DNA; revealing the molecular detail of a fast and powerful motor.
Structural and functional analysis of the protein kinase R. We have shown that protein kinase R (PKR) plays a key role in regulating the body's response to virus infections, inflammation and cancer. This project will identify mechanisms that regulate the activity of PKR and provide information useful for the development of novel drugs.
Development of a novel high yield cell-free protein expression system. Recombinant proteins are used as vaccines, drugs, and research tools, as well as food and detergent additives, comprising a A$100 billion international market. Their production requires laborious, expensive, and time-consuming construction of transgenic organisms or cells. Alternatively, recombinant proteins can be produced in extracts prepared from cells or organisms. The aim of this proposal is to develop a new technology t ....Development of a novel high yield cell-free protein expression system. Recombinant proteins are used as vaccines, drugs, and research tools, as well as food and detergent additives, comprising a A$100 billion international market. Their production requires laborious, expensive, and time-consuming construction of transgenic organisms or cells. Alternatively, recombinant proteins can be produced in extracts prepared from cells or organisms. The aim of this proposal is to develop a new technology that will make cell-free production of recombinant proteins rapid, cheap, and scalable. This will advance Australia’s intellectual leadership in the area of biotechnology and will bring numerous economic benefits by accelerating pharmaceutical development. Read moreRead less
Novel regulation of TRP channels by oxygen-dependent hydroxylation. Factor inhibiting HIF-1 (FIH-1) is an oxygen-sensing asparaginyl hydroxylase. A bioinformatic search identified specific transient receptor potential (TRP) ion channels as likely substrates. The hypothesis is that TRP channels are regulated by hypoxia, mediated through a novel mechanism of oxygen-dependent hydroxylation by FIH. The aim of this project is to investigate how hydroxylation by FIH mediates the hypoxic regulation of ....Novel regulation of TRP channels by oxygen-dependent hydroxylation. Factor inhibiting HIF-1 (FIH-1) is an oxygen-sensing asparaginyl hydroxylase. A bioinformatic search identified specific transient receptor potential (TRP) ion channels as likely substrates. The hypothesis is that TRP channels are regulated by hypoxia, mediated through a novel mechanism of oxygen-dependent hydroxylation by FIH. The aim of this project is to investigate how hydroxylation by FIH mediates the hypoxic regulation of TRP channels. Preliminary data show that the first candidate, TRPV3, is activated in hypoxia, is hydroxylated by FIH, and hydroxylation mediates changes in activity. Ion channels are important for the physiological response to hypoxia, and this project aims to define a novel mechanism for this response, with relevance to mammalian physiology.Read moreRead less
Functional Dissection of the Bacterial Replisome. This project aims to develop and use a suite of new single-molecule techniques to define how the bacterial replisome really works. The replisome is the machine that makes DNA in cells that are about to divide. Replisomes have many mechanistic challenges as they work to copy both strands of DNA at the same time. Many years of classic biochemical studies have worked out how many of these challenges are overcome. In recent years, the use of single-m ....Functional Dissection of the Bacterial Replisome. This project aims to develop and use a suite of new single-molecule techniques to define how the bacterial replisome really works. The replisome is the machine that makes DNA in cells that are about to divide. Replisomes have many mechanistic challenges as they work to copy both strands of DNA at the same time. Many years of classic biochemical studies have worked out how many of these challenges are overcome. In recent years, the use of single-molecule biophysical techniques has begun to challenge many aspects of the elegant textbook view of replisome function. This approach is expected to reveal how synthesis of the two DNA strands in different directions at the same time is coupled together and how timing mechanisms work.Read moreRead less
A functional dissection of the bacterial replisome. This project aims to study the replisome, the machine that duplicates DNA before cell division. Years of biochemical research has shown how its protein components work, but observation at the single-molecule level is needed to understand how they all work together. This project aims to combine novel single-molecule biophysical tools with state-of-the-art biochemistry to define how the bacterial replisome coordinates synthesis of the two DNA str ....A functional dissection of the bacterial replisome. This project aims to study the replisome, the machine that duplicates DNA before cell division. Years of biochemical research has shown how its protein components work, but observation at the single-molecule level is needed to understand how they all work together. This project aims to combine novel single-molecule biophysical tools with state-of-the-art biochemistry to define how the bacterial replisome coordinates synthesis of the two DNA strands and how it exchanges protein components on the fly. Expected outcomes of this project include improved understanding of a fundamental biological process, development of novel biophysical methodology, and training of the next generation of interdisciplinary scientists.Read moreRead less
New models of mitochondrial fatty acid oxidation disorders. Mitochondrial disease can affect both children and adults and is often fatal. This project will study mitochondrial function in cell types of the heart and brain to better understand how they generate energy in these tissues. This will provide new insights into mitochondrial metabolism and how defects in this process cause mitochondrial disease.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100171
Funder
Australian Research Council
Funding Amount
$200,000.00
Summary
Shared resource for protein discovery. This facility will enable the production and characterisation of proteins from all kingdoms of life that have diverse roles in fundamental biology and disease. A detailed understanding of how these proteins behave and function will be used to generate therapeutics and develop novel applications for these proteins in medicine and industry.