Structural Biology And Therapeutic Targeting Of Axon Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$1,512,250.00
Summary
The molecular mechanisms underlying SARM1 (sterile alpha and TIR 1) function will be investigated, which will allow design of inhibitors of axon degeneration, which can be developed into therapeutic agents for neurodegenerative disease. Outcomes are not only anticipated to support excellence in basic research, but have potential of assisting health sectors and the economy, by reducing the burden of prevalent neurodegenerative diseases such as peripheral neuropathies and traumatic brain injury.
Crosstalk Between The Repressive Histone Methyltransferases PRC2 And G9A: Structure-function Investigation To Open New Therapeutic Opportunities
Funder
National Health and Medical Research Council
Funding Amount
$595,205.00
Summary
The gene expression programs need to be precisely regulated and the misregulation of these programs can cause a broad range of human diseases. My research will focus on two protein complexes, which heavily contribute to the regulation of gene expression. My study will open a new path for developing new therapeutic strategies.
Circular RNAs As Genome Destabilisers In Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$2,163,220.00
Summary
Mutation of genes are hallmarks of both cancer and neurological disorders. My research group has identified roles for circular RNAs in both these processes. Now, we must close the loop by investigating the mechanism of these processes. This will inform not only why these genes are commonly mutated, but by exploiting the highly stable circular RNAs they may provide early prognostic/diagnostic biomarkers and even represent novel therapeutic targets for cancer and Huntington’s disease.
Atypical femoral fractures (AFF) are uncommon, but catastrophic, complications of the anti-osteoporosis medications, bisphosphonates. We aim to identify patients either protected from, or at risk of, AFF by identifying changes in their bone geometry, structure and quality, and genes increasing risk of these fractures. In this way, these cheap and effective anti-osteoporosis treatments can be targeted to patients at the lowest risk of AFF and alternative treatments to those at highest risk.
Reducing The Burden Of Breast Cancer Through Precision Prevention, Targeted Treatment And Enhanced Survivorship
Funder
National Health and Medical Research Council
Funding Amount
$1,491,192.00
Summary
Breast cancer affects 1 in 8 Australian women. Of all the cancers, breast cancer results in the largest number of years of healthy life lost from death and illness. My research will reduce this unacceptable burden of breast cancer for women and their families. Spanning prevention, through treatment to survivorship, it will facilitate reduced breast cancer incidence, more effective treatments and enhanced understanding of the effects of new treatments on ovarian function and fertility.
The Bacterial Type IX Secretion System In Polymicrobial Dysbiosis And Chronic Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$1,900,000.00
Summary
Periodontitis (severe gum disease) affects 1 in 3 adults and has been linked with heart attacks, cancer and dementia. I will lead a multidisciplinary team investigating the interaction between disease causing bacteria in the mouth and the immune response which results in destruction of the tooth’s supporting tissues and allows bacteria to enter the blood stream. The expected outcome is the development of a novel therapy which will stop progression of disease associated with these pathogens.
Counteracting Age-associated Neurodegenerative Diseases Using Chaperone-based Amyloid Disaggregases
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
In neurodegenerative diseases such as Alzheimer’s disease, proteins form clumps through changes in structure due to mutations or proteotoxic chemical insults. The formation of these toxic clumps causes brain cells to die prematurely triggering symptoms such as dementia. I have identified a molecular machine in human cells that efficiently clears these clumps. We are now developing strategies to activate this machine to repair damaged brain cells to slow/reserve neurodegenerative diseases.
Structural Basis For Targeting Wnt Signalling Pathway In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
Cells sense and respond to a variety of stimuli by activating different signaling pathways. The Wnt pathway is important in embryonic development as it controls cell division and specialization. In adults, dysregulation of this pathway can lead to aberrant cell division and cancer. This proposal will use structural biology to look at several steps of this pathway at the molecular level. This will provide answers on how this pathway works and will lead to new ways to target it therapeutically.
Using Protein Structure And Dynamics To Facilitate Drug Discovery
Funder
National Health and Medical Research Council
Funding Amount
$1,512,250.00
Summary
G protein-coupled receptors (GPCRs) are the largest family of membrane proteins in the human genome, and drugs targeting these receptors account for 35% of marketed drugs. This project aims to determine atomic-level structural information of how drugs bind and specifically interact with therapeutically relevant GPCRs. Outcomes of this research will facilitate the design of future development of selective and effective drugs.