Relaxin Receptor Structural Determination To Aid Therapeutic Development
Funder
National Health and Medical Research Council
Funding Amount
$1,249,114.00
Summary
The receptor for the peptide hormone relaxin, RXFP1, is being targeted by numerous drug companies for the treatment of cardiovascular disease. However, the lack of molecular detail of how relaxin binds and activates RXFP1 is hindering new drug development. We will determine the structure of the complex of relaxin bound to RXFP1 and the mechanism by which this activates cells. The knowledge gained will aid in the design of new drugs targeting RXFP1 for the treatment of cardiovascular disease.
Plasmodium falciparum is the most lethal malaria parasite that infect humans. Our work will reveal how this malaria parasite governs host tropism, fertilization and immune evasion by using the 6-cysteine family of proteins which are abundantly expressed on its surface. This proposal will explore novel ways using the smallest types of antibodies, called nanobodies, to block the function of these proteins and therefore prevent malaria infection.
Finely Tuned Glutamate Receptor Inhibitors As Novel Therapeutics For Neurodegenerative Disorders
Funder
National Health and Medical Research Council
Funding Amount
$1,168,829.00
Summary
Neurodegenerative disorders are among the leading causes of death and disease burden. New drugs are needed to treat both symptoms and disease progression. This project aims to understand the properties of different drug-like compounds to inhibit proteins on the surface of brain cells (glutamate receptors) to impact disease progression and symptoms in a preclinical disease models. The project will yield a better understanding of how best to target glutamate receptors for therapeutic effect.
Precision Molecular Diagnostics Of Single Cells By Imaging Flow Cytometry
Funder
National Health and Medical Research Council
Funding Amount
$875,110.00
Summary
We have invented a highly sensitive, new method to count and evaluate chromosomes inside cancer cells. With this world-first method we can detect abnormal chromosomes when fewer than 1 cell in 1,000 is affected. We will refine the method for assessment of blood cancers and chromosome disorders such as trisomy 21 (Down Syndrome), and commence pre-clinical testing. This is a critical step towards translating this methodology into a validated test to significantly benefit human health.
Developing Novel Agents To Prevent Tumour Recurrence In Glioblastoma
Funder
National Health and Medical Research Council
Funding Amount
$1,089,561.00
Summary
Glioblastoma is a form of brain cancer that is currently incurable. We have discovered that switching-off an enzyme called KDM4 (using 'KDM4 inhibitors') improves chemotherapy outcomes with new drugs also discovered in our laboratory. This project will examine a novel drug combination treatment for glioblastoma patients and generate evidence for initiation of clinical trials. This could initiate a novel therapy that could significantly extend patients' lives.
Developing Novel Peptide-based Therapeutics And Technologies To Mitigate Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$1,161,383.00
Summary
Fibrosis (tissue scarring) is an unmet medical problem that adversely affects both human health and medical devices. It causes organ (e.g. heart, kidney) failure leading to death. Fibrotic encapsulation causes medical device (e.g. surgical mesh) failure. Our team has discovered a peptide, B7-33, that mitigates fibrosis in the short-term. Our IDEAS grant aims to develop long-acting B7-33 therapies and, to employ long-acting B7-33 mimetics in anti-fibrotic compositions for surgical meshes.
Development Of Novel Anti-malaria Drugs That Block Parasite Invasion
Funder
National Health and Medical Research Council
Funding Amount
$1,035,623.00
Summary
Malaria is a devastating parasitic disease that kills over 400,000 people a year. Antimalarial drugs play a crucial role in helping eradicate malaria but of great concern is that parasites are becoming resistant to current drugs. We are developing drugs that prevent parasites from invading and proliferating in human blood which causes malaria. We are also discovering how the drugs work with the aim of greatly improving their performance towards clinical uptake.
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.
New Therapeutic Approaches For Genetic Skeletal Disorders
Funder
National Health and Medical Research Council
Funding Amount
$961,150.00
Summary
Genetic skeletal disorders are a significant disease burden with limited therapeutic options. We will use mouse models of cartilage and bone disorders and human induced pluripotent stem cell derived bone and cartilage 'disease in a dish' models to test repurposed FDA-approved drugs and new drug candidates as novel therapeutic strategies.
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.