Understanding Age-related Protein Aggregation. The Mechanism Of Cataract And Its Prevention
Funder
National Health and Medical Research Council
Funding Amount
$709,333.00
Summary
Cataract arises from clouding of the eye lens due to the aggregation of crystallin proteins whose high concentration and close packing facilitate lens transparency. This proposal will investigate crystallin structure and interactions to understand the reasons for cataract formation and its prevention via the design of aggregation inhibitors. The results will facilitate the development of drugs to prevent cataract and other related protein aggregation diseases, e.g. Alzheimer’s and Parkinson’s.
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
Protein Homeostasis, Protein Aggregation And Amyotrophic Lateral Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$428,065.00
Summary
There is a desperate need for biomarkers and therapeutics for Motor Neurone Disease (MND). Mutations in a growing list of genes are implicated as a cause of MND, although the way these cause MND remains a mystery. I aim to build a uniquely positioned research team that approaches this problem from a protein centric view and incorporating strategic collaborative efforts to the understanding of the pathogenesis of MND; the longterm goal of which is translation to biomarkers and therapeutics.
Prion-like Behaviour In Immunity: Super-sized Signalling Platforms?
Funder
National Health and Medical Research Council
Funding Amount
$611,995.00
Summary
Prions have been mostly associated with pathologies but recent discoveries show that prion-like behaviour may be beneficial, enhancing our immune response for example. To test this, we want to systematically explore all human proteins involved in the defence against pathogens, find new prion-like trends and probe their role in the innate immune response.
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.
The Ghost In The Machine: Understanding How Haemostasis Is Regulated By Allosteric Disulphide Bonds
Funder
National Health and Medical Research Council
Funding Amount
$898,008.00
Summary
Genes encode proteins, which are the machinery of life. All life forms make proteins that contain bonds between pairs of cysteine amino acids called disulphide bonds. Prof Hogg has discovered a type of disulphide bond, the allosteric disulphide, which controls how proteins work by breaking or forming in a precise way. His research aim is to define how haemostasis is controlled by allosteric disulphides. Haemostasis gone wrong leads to heart attack and stroke.
Most diseases are much more common in the elderly. The reasons are poorly understood. We have evidence that the most common eye diseases, cataract and presbyopia, are due to the fact that the large molecules that make up the lens do not turnover. In lenses of older people proteins, which make up the bulk of the transparent tissue, become degraded. It turns out that very long lived proteins are quite common in the body. This proposal seeks to determine what role degradation of these ancient prote ....Most diseases are much more common in the elderly. The reasons are poorly understood. We have evidence that the most common eye diseases, cataract and presbyopia, are due to the fact that the large molecules that make up the lens do not turnover. In lenses of older people proteins, which make up the bulk of the transparent tissue, become degraded. It turns out that very long lived proteins are quite common in the body. This proposal seeks to determine what role degradation of these ancient proteins has in other diseases of aging.Read moreRead less
Characterization Of Haemopoietic Lineage Determining Genes
Funder
National Health and Medical Research Council
Funding Amount
$631,021.00
Summary
Haemopoiesis is the process by which blood cells develop from stem cells. This process is tightly regulated and is dependant upon the appropriate expression of genes at each developmental stage within various lineages. Our work focuses on two genes (Mlf1 and Hls5) that are involved in determining lineage commitment and affect the expression of key hemopoietic regulators. If these genes are aberrantly expressed leukemias and other blood disorders can develop.
Modulating Sphingolipid Signalling To Enhance Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$698,447.00
Summary
Impaired wound healing is a major problem for diabetics, who often suffer with chronic unresolved wounds with serious effects on their quality of life and mortality. We have recently discovered a new pathway involving sphingolipids that shows great promise to improve wound healing in diabetics. In this project we will examine the targeting of this pathway, using existing and newly developed agents, to improve wound healing in advanced pre-clinical models of diabetes.