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.
Targeting PD-1 Expressing T-peripheral Helper (Tph) Cells And Dysregulated Checkpoint Molecules: Improving Outcomes In Rheumatoid Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$597,168.00
Summary
Rheumatoid arthritis is a chronic disease, causing pain, swelling and irreversible deformity of the joints. We propose to investigate the immune cell environment that drives this disease. In particular, we will focus on a new type of cell called Tph cells and related immune pathways. We will also study how they may be used as therapeutic targets or as markers to monitor disease activity. Our findings may translate into clinical practice and form a basis for new therapeutic strategies.
Sickle Cell Disease was the first molecular disease described in man, and is the most prevalent. In some African countries, India and the Middle East, up to 20% of the population carry the sickle gene mutation. In developing countries, 90% of children die before 5 years of age. In developed countries, patients suffer a lifetime of chronic pain and die ~20 years early. We will employ new gene editing approaches to repair the mutation or recruit fetal hemoglobin to cure SCD in human samples.
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.
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.
Presentation Of Metabolite Antigens By MR1 Molecules: A Fundamental System Of Immune Priming
Funder
National Health and Medical Research Council
Funding Amount
$883,832.00
Summary
Our immune system constantly monitors our body for disease-causing microbes, such as bacteria that cause illnesses like pneumonia or tuberculosis. Our cells have a molecular alarm-system called 'MR1' which alerts white blood cells that an infection by microbes is occurring, however this process is not well understood. This grant will allow me to discover the cells and molecular pathways that govern the MR1 alarm system, which may lead to new treatments against common diseases in our community.