Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
EPIGENETIC REPROGRAMMING OF MALIGNANT BREAST CANCER
Funder
National Health and Medical Research Council
Funding Amount
$863,268.00
Summary
Poorly differentiated breast cancers are aggressive tumors, frequently resistant to chemotherapy and associated with high morbidity. Herein we propose the engineering of more selective therapeutic agents able to target the genes involved in cancer initiation and resistance to treatment. We aim to correct and reprogram the cancer cell genome in state that is similar to normal, not tumorigenic cells. This work will generate novel forms of treatment for cancers that are presently not curable.
The protein import machinery of peroxisomes. The peroxisome is a subcellular organelle essential for cellular metabolism. Our understanding of the formation, or biogenesis, of the peroxisome has advanced to the stage where many of the proteins involved in this process have been identified. What is less clear is how these proteins interact to form functional macromolecular complexes in the cell. In this project we will use biochemical approaches to isolate protein complexes involved in peroxisome ....The protein import machinery of peroxisomes. The peroxisome is a subcellular organelle essential for cellular metabolism. Our understanding of the formation, or biogenesis, of the peroxisome has advanced to the stage where many of the proteins involved in this process have been identified. What is less clear is how these proteins interact to form functional macromolecular complexes in the cell. In this project we will use biochemical approaches to isolate protein complexes involved in peroxisome biogenesis. These studies will help to elucidate the molecular mechanisms of peroxisome biogenesis and contribute to an understanding of organelle biogenesis generally.Read moreRead less
The molecular mechanism of retromer and sorting nexin function in endosomal membrane trafficking. The proposed research represents breakthrough science that will lead to a fundamental understanding at the molecular level of the structure and assembly of the retromer complex and how it regulates sorting of receptors in the endosomal system. It will provide excellent research training for top graduate students and post-doctoral scientists in multidisciplinary methods that constitute state-of the- ....The molecular mechanism of retromer and sorting nexin function in endosomal membrane trafficking. The proposed research represents breakthrough science that will lead to a fundamental understanding at the molecular level of the structure and assembly of the retromer complex and how it regulates sorting of receptors in the endosomal system. It will provide excellent research training for top graduate students and post-doctoral scientists in multidisciplinary methods that constitute state-of the-art structural and molecular cell biology research. By addressing an area of great interest internationally the project will have the capacity to increase Australia's knowledge base and strengthen it's reputation for research excellence.Read moreRead less
The role of human single-stranded binding protein (hSSB1) in DNA damage repair and tumorogenesis. Cancer is a leading cause of disease related death world wide, accounting for over 13% of all deaths in 2007. Approximately 38,000 people died in Australia from cancer in 2005. Cancer results from a single cell losing a vital part of its genetic information, this results in the cell losing its normal programming and initiates a process of rapid growth and multiplication. This research project aims t ....The role of human single-stranded binding protein (hSSB1) in DNA damage repair and tumorogenesis. Cancer is a leading cause of disease related death world wide, accounting for over 13% of all deaths in 2007. Approximately 38,000 people died in Australia from cancer in 2005. Cancer results from a single cell losing a vital part of its genetic information, this results in the cell losing its normal programming and initiates a process of rapid growth and multiplication. This research project aims to look at the mechanisms that exist to prevent this initial loss of genetic material within an individual cell. It further aims to translate theses discoveries into the clinic, providing new tools for diagnosis and prognosis of specific cancers and to establish links with major pharmaceutical companies to develop novel anticancer therapies.Read moreRead less
Endosomal Protein Transport: From Molecular Structures to Biological Function. Intracellular transport of biomolecules through the endosomal organelle is critical for normal cellular processes such as signalling, homoeostasis and development. Defects in this fundamental process and subversion of it by bacterial and viral pathogens also lead to many different human diseases. This project will build on Australia's strong programme of structural and cellular biology research to develop key insights ....Endosomal Protein Transport: From Molecular Structures to Biological Function. Intracellular transport of biomolecules through the endosomal organelle is critical for normal cellular processes such as signalling, homoeostasis and development. Defects in this fundamental process and subversion of it by bacterial and viral pathogens also lead to many different human diseases. This project will build on Australia's strong programme of structural and cellular biology research to develop key insights into endosomal trafficking at the molecular level. Outcomes from this work will place Australia at the forefront of international efforts to understand this essential biological process and will have important implications for future design of pharmaceuticals.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100157
Funder
Australian Research Council
Funding Amount
$600,000.00
Summary
Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information th ....Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information that is not easily obtainable with other approaches. The project will enable Australian researchers to image and analyse the full complexity of biological systems, potentially transforming cell biology, drug development and understanding the molecular basis of disease. It will also demonstrate how the capacity of microscopy facilities can be enhanced and bias in imaging data reduced by automating data acquisition and mining of image-based data.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0347955
Funder
Australian Research Council
Funding Amount
$500,000.00
Summary
A Cell Sorter Facility for Neuroscience and Related Biotechnology. Neuroscience is entering an era of accelerated discovery in which Queensland neuroscientists can excel if they gain leadership in key technologies. One critical technology is the ability to obtain specific cell populations from various parts of the nervous system in sufficient quantity and purity to enable their accurate examination by gene array, proteomics and physiological techniques. The aim is to establish the world's first ....A Cell Sorter Facility for Neuroscience and Related Biotechnology. Neuroscience is entering an era of accelerated discovery in which Queensland neuroscientists can excel if they gain leadership in key technologies. One critical technology is the ability to obtain specific cell populations from various parts of the nervous system in sufficient quantity and purity to enable their accurate examination by gene array, proteomics and physiological techniques. The aim is to establish the world's first cell-sorting facility dedicated to the production of nerve cells suitable for molecular characterization and screening, providing the basis for identifying key molecules regulating brain function, ageing and repair of great importance to the biotechnology/pharmaceutical industry.Read moreRead less
SNARE-mediated perforin and cytokine release in natural killer cells. Cytotoxic cells release toxic granules and cytokine messengers to kill pathogen infected and cancerous cells and to mount immune responses. This project will investigate different SNARE molecules that regulate the secretion of perforin from granules and cytokines from other carriers, assisting in the understanding of complex but essential cellular pathways.
Formation of the Chlamydial Inclusion Requires Host Trafficking Pathways. Using cellular and biochemical approaches this project aims to examine the membrane trafficking pathways hijacked by the pathogen Chlamydia and to define the key components of these pathways. Chlamydia are obligate intracellular pathogens responsible for a range of human and animal diseases. In order to survive within the host cell, the pathogen hijacks the host's membrane trafficking pathways to engineer an intracellular ....Formation of the Chlamydial Inclusion Requires Host Trafficking Pathways. Using cellular and biochemical approaches this project aims to examine the membrane trafficking pathways hijacked by the pathogen Chlamydia and to define the key components of these pathways. Chlamydia are obligate intracellular pathogens responsible for a range of human and animal diseases. In order to survive within the host cell, the pathogen hijacks the host's membrane trafficking pathways to engineer an intracellular niche called an inclusion. In addition to providing a permissive environment, this strategy also shields the pathogen from the host's immune system.Read moreRead less