Characterisation Of The Growth Receptor Bound 7 (Grb7) Protein And Protein And RNA Partners Involved In The Regulation Of Stress Granule Formation And Cell Migration.
Funder
National Health and Medical Research Council
Funding Amount
$643,958.00
Summary
This proposal is to investigate the Grb7 protein that occurs at very high levels in some types of cancer cells, including breast cancer cells. It is thought that Grb7 contributes to the progression of cancer by directly affecting the regulation of other genes. We will investigate the way in which this protein interacts with other proteins and RNA that could underlie the cancer growth and spread. A better understanding of the Grb7 protein will help to establish its potential as a novel drug targe ....This proposal is to investigate the Grb7 protein that occurs at very high levels in some types of cancer cells, including breast cancer cells. It is thought that Grb7 contributes to the progression of cancer by directly affecting the regulation of other genes. We will investigate the way in which this protein interacts with other proteins and RNA that could underlie the cancer growth and spread. A better understanding of the Grb7 protein will help to establish its potential as a novel drug target.Read moreRead less
C-Jun N-terminal Kinase Actions In The Response To Stress
Funder
National Health and Medical Research Council
Funding Amount
$480,127.00
Summary
All cells in our body sense and respond to stressful changes in our environment. We are focused on enzymes called JNKs that relay this information, and so form part of the key response pathways. JNKs are now being evaluated as new drug targets for the treatment of diseases including diabetes and stroke, but we know very little about how JNKs work in stressed cells. We will define new partners for the JNKs and in so doing reveal new information on the stress-activated events they regulate.
Harnessing The Human Postmortem Brain To Elucidate Changes In FK506 Binding Protein (FKBP5) In The Neuropathology Of Severe Psychiatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$392,052.00
Summary
The postmortem human brain is a unique source to search for the pathological basis of severe psychiatric disorders including major depression, bipolar disorder and schizophrenia. Postmortem tissues are however being underutilised. This project will apply a selection of powerful biochemical measuring techniques to postmortem human brain tissues to uncover the molecular pathways of severe psychiatric disorders, which is knowledge that can lead to better treatments, preventions and cures.
Characterisation Of TIA Proteins In RNA Recognition And Stress Granule Formation
Funder
National Health and Medical Research Council
Funding Amount
$566,966.00
Summary
Cells in our body need to be able to respond to stresses such as heat, hypoxia, chemical stress or infection. In this project we investigate the specialized TIA proteins that have the job of protecting RNA in stressed cells. We will investigate the way TIA proteins recognize particular mRNA and form temporary protective clusters. By better understanding this process we will gain insight into the way in which cells are susceptible to damage in diseases including neurodegenerative disease.
Interactions Between Advanced Glycation And Oxidative Stress In Diabetic Renal And Cardiac Complications
Funder
National Health and Medical Research Council
Funding Amount
$431,700.00
Summary
Kidney and heart disease are serious complications of diabetes. These complications are the major cause of disability and premature death in the western world. Studies from our group and others have shown that diabetic complications appear to be a consequence of a number of different processes. These pathways include a sugar dependent pathway of irreversible interactions between proteins such as collagen and sugar known as advanced glycation. The process of advanced glycation alters the body's a ....Kidney and heart disease are serious complications of diabetes. These complications are the major cause of disability and premature death in the western world. Studies from our group and others have shown that diabetic complications appear to be a consequence of a number of different processes. These pathways include a sugar dependent pathway of irreversible interactions between proteins such as collagen and sugar known as advanced glycation. The process of advanced glycation alters the body's ability to renew these protein, hence causing accelration of the ageing process. In fact, it is estimated that this process occurs almost fifty times faster in diabetes. These sticky complexes accumulate in tissues causing disruption ot the normal tissue structure. Our group has a drug which can act as scissors and cut the sticky sugar off the proteins allowing it to be turned over. Unfortunately this does not fix all of the damage. These AGE molecules are involved in a number of other harmful processes including the production of toxic oxygen derived molecules which are harmful byproducts of diabetes. While these oxygen 'radicals' have been implicated in heart attack and stroke their source has remained a mystery in diabetes. Previously, the only way to remove these molecules was to mop them up with antioxidants such as Vitamin E. Antioxidants work slowly and so some damage is already done before they 'detoxify' these oxygen radicals. We propose to use combinations of medicines to see if we can achieve more effective protection against these processes in experimental diabetes. This may provide new therapies for threatment of kidney and heart disease in diabetes.Read moreRead less
Structure-function Inter-relationships Of Small Heat-shock Chaperone Proteins
Funder
National Health and Medical Research Council
Funding Amount
$240,990.00
Summary
In vivo, most proteins only function over a narrow temperature or pH range. For example, if the solution containing a particular protein is heated (stressed), the protein will unfold, aggregate and potentially precipitate. The act of protein precipitation is an irreversible process that, in many cases, has deleterious consequences for cell viability. Protein precipitation is associated with a diversity of diseases, e.g. cataract and neurodegenerative diseases such as Alzheimer's, Creutzfeldt-Jak ....In vivo, most proteins only function over a narrow temperature or pH range. For example, if the solution containing a particular protein is heated (stressed), the protein will unfold, aggregate and potentially precipitate. The act of protein precipitation is an irreversible process that, in many cases, has deleterious consequences for cell viability. Protein precipitation is associated with a diversity of diseases, e.g. cataract and neurodegenerative diseases such as Alzheimer's, Creutzfeldt-Jakob and Parkinson's diseases. Nature has evolved cellular mechanisms to minimise protein misfolding, aggregation and precipitation which principally utilise a diverse group of controlling or regulatory proteins called molecular chaperones. Amongst the most important of these are the small heat-shock proteins (sHsps) which are found in all organisms. sHsps function by interacting in a very efficient manner with destabilised proteins to prevent their precipitation. Little is known, however, about the structure of sHsps nor the mechanism by which they perform their chaperone action. This proposal will address these fundamental aspects via the use of a variety of spectroscopic techniques, principally nuclear magnetic resonance (NMR) spectroscopy.Read moreRead less