GPR88 As A Novel Target For Fronto-striatal Dysfunction In Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$606,966.00
Summary
GPR88 is a protein that is specifically found in the striatum, one of the main brain regions involved in schizophrenia. Studies in mice have showed that GPR88 may have a role in learning and memory; our early studies show that GPR88 controls the activity of a population of cells in the striatum. This project will determine the mechanism by which GPR88 controls the function of the striatum and how this translates into regulating brain circuitry and learning and memory relevant to schizophrenia.
Translating Membrane Proteins Into Therapeutics; From Bedside To Bench
Funder
National Health and Medical Research Council
Funding Amount
$9,466,000.00
Summary
Membrane proteins are the principal gatekeepers for control of cellular response, with G protein-coupled receptors (GPCRs) the largest family of cell surface proteins. These proteins are critically important for pathophysiological control, and are a major target for drug discovery. Nonetheless drug attrition due to lack of clinical efficacy remains high. We are combining cell biology, clinical management and drug discovery science to enable more effective therapeutic translation.
Positive Allosteric Modulation Of Metabotropic Glutamate Receptor 5; A Novel Approach For The Treatment Of Schizophrenia And Cognitive Disorders
Funder
National Health and Medical Research Council
Funding Amount
$348,428.00
Summary
The metabotropic glutamate receptor subtype 5 (mGluR5) has emerged as an exciting new target for the treatment of schizophrenia and cognitive disorders. We will investigate novel drug-binding sites on these receptors with the aim to discover new therapeutics. These studies also aim to definitively characterize mGluR5 activity following treatment with novel compounds to improve our understanding of the normal function of these important receptors.
Physiological And Neurochemical Mechanisms Of Executive Control
Funder
National Health and Medical Research Council
Funding Amount
$285,500.00
Summary
This study will examine how manipulating brain chemistry influences our ability to inhibit behaviour and monitor our own performance errors. We will determine the response of the brain using the physiological techniques of event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI). The first technique allows us to determine how drugs influence the timing of neural events, while the second technique allows us to determine where in the brain these drugs act.
The Role Of Cellular Microdomains In G-protein Coupled Receptor Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$385,297.00
Summary
Molecules communicate with cells by attaching to proteins called receptors on the outside of cells, and triggering a series of events inside the cell. These events initially include the assembly of multiple proteins at the cell surface. This project will examine the formation of receptors and other proteins into these ‘communication complexes’. This will provide novel targets for more selective drug development.
Modification Of The Microbiome And Utilisation Of Microbial Products As Novel Treatments For COPD
Funder
National Health and Medical Research Council
Funding Amount
$1,226,338.00
Summary
Smoking leads to lung inflammation that causes emphysema - a major health problem in Australia. Emphysema progressively declines even if smoking stops and there are no treatments. Recently changes in gut microbes have been linked to inducing or protecting against inflammation in the gut and lung. Thus we may be able to control inflammation by modifying these gut microbiomes. We may be able to ingest specific microbes or use specific antibiotics or other factors as new treatments for emphysema.
Relaxin Signalling In The Endometrium And The Regulation Of Early Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$466,125.00
Summary
Relaxin is a hormone, that is made in the ovary and the uterus, and plays a very important role in supporting the growth and development of the uterus so that the young embryo can implant properly. In fact, early pregnancy loss is associated with altered levels of relaxin in the blood. Very little is known about how relaxin works in the uterus. This project aims to address this important function, and makes use of cultured uterine cells prepared from tissues taken from women undergoing hysterect ....Relaxin is a hormone, that is made in the ovary and the uterus, and plays a very important role in supporting the growth and development of the uterus so that the young embryo can implant properly. In fact, early pregnancy loss is associated with altered levels of relaxin in the blood. Very little is known about how relaxin works in the uterus. This project aims to address this important function, and makes use of cultured uterine cells prepared from tissues taken from women undergoing hysterectomy for fibroids or similar illnesses. When these cells are grown in culture, we can mimic in vitro many of the events that occur in early pregnancy, causing the cells to differentiate and grow just as they would in vivo. Relaxin appears to exert its important effects on these cells by causing the concentration of the second messenger cAMP in the so-called stromal cells to increase greatly and in a sustained manner. It is this cAMP which is then responsible for many of the changes which are essential for healthy pregnancy. A knowledge of the molecular mechanisms behind these effects would help us firstly to understand how the uterus becomes receptive to an implanting embryo, and may explain why some women lose their babies in early pregnancy, or develop some of the negative symptoms associated with placental development such as growth restriction and preeclampsia. Relaxin appears to stimulate cells through the mediation of a new type of cell surface receptor, called LGR7. Whilst structurally this receptor looks like those for many other hormones, belonging to the group of so-called G-protein coupled receptors, it does not behave like these in natural uterine cells. Instead it appears to make use of completely new signaling pathways inside the cells. This project aims to unravel and understand these new pathways, thus providing information not only of importance for diagnosis and treatment of early pregnancy problems, but also of relevance for all other similar receptors.Read moreRead less
Understanding New Drug Paradigms At M1 Muscarinic Receptors.
Funder
National Health and Medical Research Council
Funding Amount
$334,053.00
Summary
The M1 muscarinic receptor is a brain protein that plays vital roles in memory, and has been implicated in Alzheimer�s and schizophrenia. However, this protein remains poorly targeted by current medications. The current proposal will investigate the mechanisms of action of a new class of more selective M1 receptor drugs. Our studies will generate valuable information that is directly relevant to the pharmaceutical industry and academic drug discovery.