Understanding Transcription Factor Interactions In Blood Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
All blood cells develop from the same parent cells, which are known as stem cells. Once the decision is made for a stem cell to develop into a particular type of blood cell, mechanisms must exist that ensure the cell only expresses the genes that are appropriate for that cell type. These mechanisms involve the action of proteins known as transcription factors, which specifically activate the expression of the correct genes. While deregulation of these control mechanisms often leads to diseases s ....All blood cells develop from the same parent cells, which are known as stem cells. Once the decision is made for a stem cell to develop into a particular type of blood cell, mechanisms must exist that ensure the cell only expresses the genes that are appropriate for that cell type. These mechanisms involve the action of proteins known as transcription factors, which specifically activate the expression of the correct genes. While deregulation of these control mechanisms often leads to diseases such as cancer, unfortunately our understanding of how networks of transcription factors combine to direct processes such as blood cell development is relatively poor. GATA-1 and PU.1 are essential for the normal development of erythroid and myeloid blood cell types, respectively, and the work in the present proposal is aimed at understanding some of the molecular details of how direct interactions between these two proteins modulate their activity. This information should prove useful in understanding other transcriptionally regulated systems and may eventually help provide a route to treating a number of classes of blood cancer.Read moreRead less
Improving The Bioavailability Of Peptide-based Therapeutics For The Treatment Of Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$341,123.00
Summary
Many diseases are controlled at the molecular level by proteins and their interactions with other proteins. Harmonin is a key protein in Usher syndrome, the most common form of deaf-blindness in humans, and harmonin has similarities to some proteins involved in Alzheimer’s disease. We seek to understand how harmonin works. The findings of this study may lead to new treatments for deaf-blindness and Alzheimer’s disease.
Regulation Of Caspase-1 Activation And Inflammation By PYD And CARD Proteins
Funder
National Health and Medical Research Council
Funding Amount
$364,549.00
Summary
Inflammatory diseases such as rheumatoid arthritis are among the largest contributors to health expenditure in Australia, and the impact of these diseases will increase dramatically over the next 15-20 years as the population ages. This research will reveal new insights into the regulation of caspase-1 activation and secretion of interleukin-1b, the primary cause of chronic and acute inflammation, and will enhance future approaches for development of treatments for inflammatory disease.
I am a structural biologist specialising in nuclear magnetic resonance spectroscopy who is primarily studying the properties and applications of proteins and peptides in drug design.
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