Enhancing The Immune Response To Disordered Malaria Antigens
Funder
National Health and Medical Research Council
Funding Amount
$643,739.00
Summary
Half of the worlds population live at risk of malaria, and the disease kills half a million people a year, predominantly young children. Despite recent progress, a vaccine with the efficacy required to help control and ultimately eradicate malaria remains out of reach. This project studies an important class of proteins likely to form part of a future malaria vaccine, and will develop new ways to improve their effectiveness as vaccine components.
It is estimated that one quarter of people over the age of 65 suffer from some form of memory impairment, mostly in the form of AlzheimerÍs disease. The enormous economic and social costs of the disease and an aging population make it a major health problem. This work will lead to atomic structures of proteins centrally involved in the disease, thus increasing our understanding of the molecular mechanisms of the disease and form the basis for the design of drugs to combat it.
Resolving And Targeting The Complex Molecular Mechanisms Underlying GPCR Signalling
Funder
National Health and Medical Research Council
Funding Amount
$1,071,370.00
Summary
Receptors are located on the surface of all human cells to allow our cells to respond to their environment. Over 30% of prescription drugs act through particular receptors called GPCRs, however effective drugs without side effects are difficult to develop because we do not have a deep understanding of how GPCRs transmit complex signals. In this proposal we seek to resolve the atomic-level details of GPCR signalling to assist in the development of better drugs for a diverse range of diseases.
Rational Development Of Novel Analgesics For The Treatment Of Chronic Pain
Funder
National Health and Medical Research Council
Funding Amount
$595,945.00
Summary
Chronic pain is a major global health problem that currently affects over three million Australians. There are few drugs available for treatment of chronic pain and most have significant side-effects. Individuals lacking a particular type of ion channel known as Nav1.7 are completely insensitive to pain, but are otherwise normal. Block of this channel therefore appears to be an ideal avenue for pain relief. This project aims to produce selective Nav1.7 blockers that can be used as analgesics for ....Chronic pain is a major global health problem that currently affects over three million Australians. There are few drugs available for treatment of chronic pain and most have significant side-effects. Individuals lacking a particular type of ion channel known as Nav1.7 are completely insensitive to pain, but are otherwise normal. Block of this channel therefore appears to be an ideal avenue for pain relief. This project aims to produce selective Nav1.7 blockers that can be used as analgesics for treating chronic pain.Read moreRead less
A New Class Of Anti-Malarial Agents Targetting Apical Membrane Antigen
Funder
National Health and Medical Research Council
Funding Amount
$597,598.00
Summary
Malaria is a major global health problem that imposes a substantial burden on the world’s most vulnerable societies. The invasion of host cells by malaria parasites represents an attractive target for therapeutic intervention, and Apical Membrane Antigen 1 (AMA1) plays an essential role in this process. Agents that bind to a key interaction site on AMA1 prevent host cell invasion and thus represent starting points for the development of a new class of anti-malarial drugs.
Inhibitors Of Inducible Nitric Oxide Synthase (iNOS) Regulation As A Basis For Novel Anti-Infective Agents
Funder
National Health and Medical Research Council
Funding Amount
$643,735.00
Summary
The human enzyme iNOS generates reactive nitrogen species that are required for the intracellular killing of pathogens such as bacteria and parasites. Recently, we showed that the SPSB proteins are key regulators of this important enzyme, and that interfering with this regulation enhanced the anti-microbial actions of iNOS. This project will develop small molecule inhibitors of the SPSB-iNOS interaction for use as novel anti-infective agents in humans.
Roles Of The Nuclear Growth Hormone Receptor In Cell Proliferation And Survival
Funder
National Health and Medical Research Council
Funding Amount
$429,387.00
Summary
We have discovered that the cell surface receptor for growth hormone travels to the cell nucleus in dividing cells, including cancer cells. Given the role of growth hormone in promoting growth postnatally, we seek to uncover how the nuclear receptor promotes proliferation directly, and by gene splicing. We have identified strong candidates for its direct actions through proteomics, and a DNA binding site for the receptor. Here we will investigate its role in proliferation, gene splicing and DNA ....We have discovered that the cell surface receptor for growth hormone travels to the cell nucleus in dividing cells, including cancer cells. Given the role of growth hormone in promoting growth postnatally, we seek to uncover how the nuclear receptor promotes proliferation directly, and by gene splicing. We have identified strong candidates for its direct actions through proteomics, and a DNA binding site for the receptor. Here we will investigate its role in proliferation, gene splicing and DNA strand break repair after cell irradiation.Read moreRead less
Towards The Rational Design Of Calcium Sensing Receptor Allosteric Modulators For The Treatment Of Osteoporosis And Calcium Handling Disorders
Funder
National Health and Medical Research Council
Funding Amount
$741,390.00
Summary
Drugs that target the human calcium sensing receptor can be too strong or too weak, resulting in side effects or lack of efficacy. This proposal thus seeks to establish whether the strength of drug activity can be rationally altered and exploited to treat different disease states by fine-tuning CaSR activity in a disease-specific manner.
Cancer Risks From Low-dose Ionising Radiation Following Diagnostic Medical Procedures
Funder
National Health and Medical Research Council
Funding Amount
$750,579.00
Summary
Our study investigates cancer risk following exposure to low doses of ionising radiation from medical procedures. Our first major paper linked over 800,000 CT exposures to cancer outcomes in a cohort of almost 11 million young Australians, and found that CT exposure predicted an increased incidence of leukaemia and most solid cancers. In our ongoing work we will incorporate nuclear medicine and other diagnostic x-rays, and estimate radiation dose for individual procedures and to specific organs.
Determinants Of Tissue- And Ligand-Specific Responses At The Mineralocorticoid Receptor
Funder
National Health and Medical Research Council
Funding Amount
$668,485.00
Summary
The steroid hormone aldosterone controls salt balance and hence, blood pressure. It also has been shown to have a significant role in cardiac failure. Although drugs that block the aldosterone receptor are beneficial in the treatment of heart failure, they are limited by potassium retention in the kidney. In order to develop tissue-specific blockers of the aldosterone receptor, it is necessary to identify mechanisms by which the receptor can be activated and/or blocked in specific tissues.