What Factors Affect Lesion Distribution In Multiple Sclerosis And Experimental Autoimmune Encephalomyelitis?
Funder
National Health and Medical Research Council
Funding Amount
$56,797.00
Summary
Multiple sclerosis (MS) is a common neurological disease which affects about 10,000 people in Australia. In MS, a persons own immune system starts to attack specific parts of their brain and spinal cord, causing lesions that prevent nerve impulses from passing from the brain to other parts of the body. The symptoms that people with MS develop can vary from one person to another, depending on where in the brain or spinal cord the lesions occur. Some parts of the brain and spinal cord seem to be m ....Multiple sclerosis (MS) is a common neurological disease which affects about 10,000 people in Australia. In MS, a persons own immune system starts to attack specific parts of their brain and spinal cord, causing lesions that prevent nerve impulses from passing from the brain to other parts of the body. The symptoms that people with MS develop can vary from one person to another, depending on where in the brain or spinal cord the lesions occur. Some parts of the brain and spinal cord seem to be much more susceptible to this attack than others, and the question that this study will address is why do lesions occur where they do in MS? Some preliminary results strongly suggest that there is a link between carrying particular genes that control immune responses, having immune cells that can attack one particular protein in the nervous system called PLP, and developing lesions in parts of the brain that control balance. This will be investigated further, and we will also look for other links between immune cells that can attack other proteins and development of lesions in particular areas. If such links can be identified, they would be very important for improved diagnosis of MS and it would enable more specific treatments for MS to be developed. We will also use experimental models of MS to investigate the exact components within the nervous system and within the immune system that play a role in directing the attack to particular sites.Read moreRead less
Role Of Hsp40 And Hsp70 In Huntingtin Misfolding, Oligomerization And Inclusion Assembly
Funder
National Health and Medical Research Council
Funding Amount
$590,103.00
Summary
Huntington disease results from a mutation that causes the Htt protein to become abnormally sticky and form toxic clusters in neurons. Cells have natural defences to clustering with proteins called chaperones, which are exciting therapeutic targets. This project will examine how chaperones defend against toxic Htt clustering with cutting-edge imaging technologies. The knowledge gained will aid in designing therapeutic strategies that stimulate the defence processes and suppress the clusters.
Developing Novel Molecules That Target Hormone Receptors As An Alternative Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$459,867.00
Summary
A promising class of cancer drugs target heat shock protein 90 (Hsp90) and prevent Hsp90 from maintaining its ~100 proteins involved in cell growth. However, all current Hsp90 chemotherapeutics non-selectively target proteins maintained by Hsp90, and induce a cell rescue mechanism involving Hsp70. We describe the development of a novel molecule that will selectively control cell growth and prevent cell rescue via a unique Hsp90 regulated mechanism.
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.
Directed Molecular Evolution Of G Protein-coupled Receptors For Stable And Functional Expression In Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$383,479.00
Summary
Approximately half of all prescription drugs on the market act on G protein coupled receptors (GPCRs). The mechanisms underlying GPCR function are mainly unknown due to a lack of structural information. No solved structures exist for any of the estimated 800 human GPCRs, making it difficult to design new drugs. By applying advanced protein engineering techniques I aim to produce human GPCRs in bacteria to ultimately acquire structural information, which will enable novel drug development.
Disrupting Mucin-mucin Interactions To Treat Respiratory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$480,531.00
Summary
Diseases like asthma, emphysema and cystic fibrosis all feature the overproduction of mucus in the lungs that make it very difficult for patients to breathe and increases their susceptibility to infections. Few therapies are available for thinning this mucus, which is made thick by a network of linkages between proteins. We are studying these linkages and developing methods to break them up. This research could yield new mucus-thinning drugs to treat lung diseases.
Mechanisms Regulating Mitochondrial Outer Membrane Permeabilisation During Programmed Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$306,562.00
Summary
Apoptosis is a form of cell suicide that is vital in human development and health by removing damaged or unwanted cells in a regulated manner. Disturbances in this pathway are known to be the cause of cancers and other diseases. This research will investigate how the pivotal step in cell death, termed mitochondrial outer membrane permeabilisation (MOMP) is regulated.