Structural And Functional Characterisation Of The Oncogene P-Rex1
Funder
National Health and Medical Research Council
Funding Amount
$623,447.00
Summary
The spread of cancer to other parts of the body (metastasis) is a major cause of mortality. The characterisation of proteins that regulate metastasis is therefore a priority. P-Rex1 plays a crucial role in promoting metastasis in breast and other cancers. We will determine the structural basis of P-Rex1 activity, and investigate how its dysregulation promotes aberrant cell growth. This study will provide the knowledge to build future drug development programs targeting P-Rex1 in cancer.
Investigation Of Two GPCRs Implicated In Tumour Progression: PAR1 And LGR5
Funder
National Health and Medical Research Council
Funding Amount
$404,689.00
Summary
G-protein-coupled-receptors (GPCRs) belong to a large and diverse family of membrane proteins. Due to their number, diversity and critical roles in signaling, GPCRs offer extraordinary opportunities for development of novel drugs. However, our rudimentary understanding of their mechanism of activation and subsequent signaling do not support rational drug design. This project focuses on two receptors, PAR-1 and LGR5, to gain insights into the activation mechanisms and signalling of GPCRs.
Molecular Determinants Of Drug Binding And Selectivity At Muscarinic Acetylcholine Receptors
Funder
National Health and Medical Research Council
Funding Amount
$816,866.00
Summary
G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors in the human genome, and drugs targeting these receptors account for 30% of marketed drugs. This project aims to determine high resolution structural information on how drugs bind and specifically interact with GPCRs, which will enable future development of selective and effective drugs.
Structural Characterisation Of Long Non-Coding RNA Bound Histone Modification Complexes
Funder
National Health and Medical Research Council
Funding Amount
$320,891.00
Summary
Cancer is a disease associated with genetic and epigenetic changes of DNA. Epigenetics involves external changes to the DNA, switching processes “on” and “off”, to regulate gene expression. This project aims to provide powerful insight into key processes involved in epigenetic-based carcinogenesis, and thereby lay the foundation for producing novel cancer diagnostic markers and molecular based therapies.
The Molecular Basis Of G Protein Coupled Transport
Funder
National Health and Medical Research Council
Funding Amount
$495,938.00
Summary
G proteins are molecular switches in all organisms, turning fundamental processes on and off . Defects in the functions of these switches can lead to severe diseases, such as cancer. Crucial details regarding the mechanism by which these switches are turned to on are still missing. This proposal will use a bacterial model system, with aims to provide structural and functional detail on the molecular mechanism of the switch in G proteins, and to extend this model to mammalian systems.
Characterisation Of TIA Proteins In RNA Recognition And Stress Granule Formation
Funder
National Health and Medical Research Council
Funding Amount
$566,966.00
Summary
Cells in our body need to be able to respond to stresses such as heat, hypoxia, chemical stress or infection. In this project we investigate the specialized TIA proteins that have the job of protecting RNA in stressed cells. We will investigate the way TIA proteins recognize particular mRNA and form temporary protective clusters. By better understanding this process we will gain insight into the way in which cells are susceptible to damage in diseases including neurodegenerative disease.
Molecular Basis For RIG-I Like Receptor Activation Of The Innate Immune Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$564,770.00
Summary
This project is to understand how proteins in the cell detect the presence of invading viruses, and pass on the message for the cell to produce defence molecules. The overproduction of these defence molecules can lead to inflammatory diseases. This research will help us to understand the process of the innate immune response in cells and how we might control it in disease states.
DBHS Protein RNA Interactions In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$748,073.00
Summary
In cells involved in cancer, the interactions of DBHS proteins with each other, and with nucleic acids (eg RNA) are different to those in healthy cells. Only once we understand how DBHS proteins interact with some important RNA molecules, and how these interactions affect cell biology, can we begin to open up new pathways for therapy. This proposal aims at understanding and explaining this complex aspect of biology.
Mechanisms Of Gene Regulation - Structure, Function And Design
Funder
National Health and Medical Research Council
Funding Amount
$697,209.00
Summary
The human genome contains at least 20000 genes. The activity of these genes must be tightly controlled throughout an individual’s life and problems with the regulation of genes lie at the heart of many common and serious diseases, including most forms of cancer. My program of research is focused on understanding the mechanisms underlying gene regulation and on the design of new reagents that could be used to manipulate the activity of genes that behave aberrantly in disease states.
Modulation Of Gene Regulation By DBHS Protein Interactions
Funder
National Health and Medical Research Council
Funding Amount
$443,244.00
Summary
The DBHS family of proteins have been shown to affect, in a novel manner, the way human cells control which genes are made into proteins - a fundamental process in healthy and cancerous cells. This project will employ cutting edge structural, molecular and cellular techniques to determine how these protein molecules interact with each other and with important gene regulatory proteins to determine cell fate.