Alzheimer's, Huntington's and Parkinson's diseases involve the formation of protein aggregates, termed amyloid. The formation of amyloid leads to cell death and neurodegeneration. The most important cellular events perturbed by the formation of amyloid aggregates are unclear. Recent evidence suggests that sterols (including cholesterol) have an important role in cellular toxicity. This study will examine the molecular basis for this, enhancing our understanding of the amyloid diseases and could ....Alzheimer's, Huntington's and Parkinson's diseases involve the formation of protein aggregates, termed amyloid. The formation of amyloid leads to cell death and neurodegeneration. The most important cellular events perturbed by the formation of amyloid aggregates are unclear. Recent evidence suggests that sterols (including cholesterol) have an important role in cellular toxicity. This study will examine the molecular basis for this, enhancing our understanding of the amyloid diseases and could suggest novel therapeutic avenues.Read moreRead less
Pathogenic And Adaptive Molecular Interactions With Mutant Huntingtin Exon 1
Funder
National Health and Medical Research Council
Funding Amount
$727,117.00
Summary
This project aims to determine how the gene mutation that causes Huntington’s disease (HD) damages cells in the brain. The diseased gene creates a protein that is abnormally sticky, which causes it to form clumps. Our goal is to determine the components of the cell that are disrupted and damaged as clumping happens. Understanding this link will enable therapeutics to be logically designed in efforts to prevent harm to the brain, potentially before symptoms are evident.
HtrA4-induced Endothelial Dysfunction In Early-onset Preeclampsia
Funder
National Health and Medical Research Council
Funding Amount
$86,073.00
Summary
Preeclampsia (PE), a life-threatening disorder of pregnancy, is characterized by a sudden increase in blood pressure in association with wide-spread endothelial dysfunction. Placenta-derived factors are believed to cause PE development. Our recent studies have identified that HtrA4, a placenta-specific serine protease may contribute to endothelial dysfunction. This study will investigate the mechanisms of HtrA4-induced endothelial dysfunction.
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.
Mechanisms Of Gene Regulation - Structure, Function And Design
Funder
National Health and Medical Research Council
Funding Amount
$697,209.00
Summary
The human genome contains at least 20000 genes. The activity of these genes must be tightly controlled throughout an individual’s life and problems with the regulation of genes lie at the heart of many common and serious diseases, including most forms of cancer. My program of research is focused on understanding the mechanisms underlying gene regulation and on the design of new reagents that could be used to manipulate the activity of genes that behave aberrantly in disease states.
Design And Engineering Of Adnectins For Diagnosis And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$803,152.00
Summary
This project aims to engineer a naturally-occurring human protein, called an adnectin, to produce molecules that are able to bind specific targets in the human body, and as such may be used in the diagnosis and therapy of a range of diseases.
Investigation Of Neuregulin Precessing By Beta-site APP Cleaving Enzyme And Gamma Secretase In Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$46,715.00
Summary
Schizophrenia (SCZ) is a complex psychiatric disorder that appears in male and female around adulthood. To date there is no clear pathological symptoms to identify SCZ individuals and place them in a specific group. Some proteins are genetically associated with this disease. I will investigate how some of these proteins disturb the function of the brain in human. My recent published data shows decrease of one of the proteins in the brain of SCZ group. My project may help develop novel and more s ....Schizophrenia (SCZ) is a complex psychiatric disorder that appears in male and female around adulthood. To date there is no clear pathological symptoms to identify SCZ individuals and place them in a specific group. Some proteins are genetically associated with this disease. I will investigate how some of these proteins disturb the function of the brain in human. My recent published data shows decrease of one of the proteins in the brain of SCZ group. My project may help develop novel and more selective therapies with less side-effects.Read moreRead less
The proposed research project involves a fundamental biochemical and biophysical investigation of a protein (ABCA4) intimately involved in the visual process. The precise role of ABCA4 in vision has not yet been elucidated, although evidence suggests a role as a lipid translocase in the retinal regenerative pathway. Our primary objective is to provide direct evidence for this putative role.
Generating An Effective Vaccine Response Against The Intrinsically Unstructured Malaria Antigen Merozoite Surface Protein 2
Funder
National Health and Medical Research Council
Funding Amount
$678,774.00
Summary
The malaria surface protein MSP2 is a promising candidate for inclusion in a malaria vaccine, having shown evidence of protection in phase IIb studies. Our goals are to identify the structural basis for the differential induction of human immune responses to native and recombinant MSP2 and to utilise this information to generate an MSP2 vaccine able to evoke a more effective anti-malarial response.
How Do BET Bromodomain Proteins Regulate Gene Expression?
Funder
National Health and Medical Research Council
Funding Amount
$586,791.00
Summary
This project is aimed at defining the biochemical mechanisms of action of a class of gene regulatory proteins (BET proteins) that are currently considered to be exciting drug targets for a range of diseases, predominantly cancer. A better understanding of the means by which BET proteins regulate gene expression will be important for the rational design and application of drugs that selectively target the proteins.