The Collagen-rich Matrix As A Driver Of Breast Cancer Progression And Resistance To Therapy
Funder
National Health and Medical Research Council
Funding Amount
$702,230.00
Summary
The extracellular matrix or 'matrix' surrounds all cells and is very important in controlling cell behaviour. In cancer, the matrix is dramatically altered, making cancer more aggressive. We recently developed a new way to study the matrix in breast cancer, and have analysed the matrix at different stages (Early/Mid/Late). We have uncovered exciting new matrix targets associated with more aggressive tumours. This project will validate their potential as therapeutic targets in breast cancer.
Harnessing Extracellular Matrix Remodelling By Cancer-Associated Fibroblasts To Increase T Cell Infiltration Of Solid Tumours
Funder
National Health and Medical Research Council
Funding Amount
$923,407.00
Summary
The ability of killer T cells to find and eliminate tumour cells is the basis for adoptive transfer immunotherapies, which thus far only work well with blood-borne cancers. There is limited success with solid tumours, which T cells do not readily infiltrate, notably because of remodelling by fibroblasts. We have discovered that T cells migrate in tunnels dug in the tumour matrix by fibroblasts. Here, we will harness this discovery to improve tumour infiltration and rejection of solid tumours.
Casting The Net: A New Approach To Identify Therapeutics To Treat Type-2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$1,068,283.00
Summary
The discovery of treatments for type-2 diabetes (T2D) is a national health priority. In T2D, cells in the brain become 'insulin resistant' resulting in dangerously high blood sugar levels. There are no treatments for brain insulin resistance. The extracellular structures that surround brain cells undergo change in T2D, resulting in insulin resistance. By furthering understanding of these extracellular brain structures, this proposal will identify new drug targets to treat T2D.
Investigating The Role Of Mitochondrial Tom40 In Regulated Cell Death And Neurodegeneration.
Funder
National Health and Medical Research Council
Funding Amount
$972,660.00
Summary
Mitochondria are internal compartments of cells, separated by bounding membranes. They are crucial to the life and death of cells, and to quality of human life and ageing. Diseases of the nervous system can be caused when mitochondria do not function properly. Our aim is to discover why a protein complex called TOM embedded in the bounding membrane is linked to dementia in some people. This will also lead to a better general understanding of the connection between mitochondria and human health.
Bivalent Analgesics: Rational Design Of Selective Ion Channel Inhibitors With Optimised Mechanism Of Action
Funder
National Health and Medical Research Council
Funding Amount
$904,890.00
Summary
The so-called 'opioid crisis' leading to the death of millions of people worldwide has highlighted the urgent need for development of novel safe and efficacious pain killers without addictive potential. This proposal aims to rationally design novel analgesic compounds by linking different classes of ion channel modulators with desirable properties.
Biosensor Based Clinical-decision Support For Patients With Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$691,933.00
Summary
Heart Failure (HF) is a progressive disease and a major global public health concern. HF accounts for a substantial number of hospitalisations, major healthcare resource utilisation and costs. We aim to engineer biosensor platform to stratify the risk in HF patients will revolutionise current management of HF by providing the cardiologist information to risk stratify patients based on protein signature. This will lead to a substantial paradigm shift in clinical practice.
Molecular Characterisation Of The DBHS Proteins In Telomerase Assembly
Funder
National Health and Medical Research Council
Funding Amount
$686,246.00
Summary
Telomerase is an enzyme that is active in over 90% of cancers. Telomerase activity allows cancer cells to divide an indefinite number of times. We have identified a novel role for the DBHS protein family in regulating telomerase activity. We aim to investigate the mechanisms by which these proteins function to assemble and transport telomerase to its site of action in the cell. We then aim to develop chemical inhibitors of these proteins, and test their utility in preventing cancer cell growth.
Validating CaMKK2 As A Rational Treatment Target For Bipolar Disorder
Funder
National Health and Medical Research Council
Funding Amount
$688,175.00
Summary
Bipolar disorder is a disabling, chronic mental illness that profoundly impairs the ability of affected individuals to function in daily life. Existing treatments for bipolar disorder are inadequate and lack the necessary efficacy and tolerability required for long-term therapy. This project will validate the enzyme, CaMKK2, as a rational treatment target for bipolar disorder, which will guide the development of more effective and safer drugs to improve patient outcomes.
Repurposing And Re-optimising Drugs That Disrupt Glycoprotein Folding To Treat COVID-19
Funder
National Health and Medical Research Council
Funding Amount
$1,199,874.00
Summary
As of June 2020, COVID-19 has infected over 7.3 million people and killed over 413,000 in the six months since it emerged. It has pushed many healthcare systems and economies to breaking point. We recently discovered that a known drug is effective at stopping the virus under laboratory conditions. This research will determine exactly how the drug works, evaluate it's potential in pre-clinical models, and re-optimise the drug's antiviral properties to ensure that we can prevent future pandemics.
ER Stress-Unfolded Protein Response A Critical Metabolic Pathway For Airway Remodelling In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$789,475.00
Summary
Airway remodelling in asthma is associated with poor clinical outcomes and is not prevented by current treatments. We have found endoplasmic reticulum stress (ERS) and associated unfolded protein response (UPR), a crucial process involve in cellular protein folding, play a key role in airway remodelling in asthma. This study will investigate whether inhibition of ERS prevents goblet cell metaplasia, mucus hypersecretion and fibrosis and can be used as a therapeutic strategy for severe asthma.