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.
Throughout our lives cells must die and be replenished. One way multicellular organisms remove unwanted cells is through a process called programmed cell death. This process eliminates redundant, damaged or infected cells by a program of cell suicide. We are studying the underlying molecular mechanisms of this cell suicide in order to design new pharmaceuticals to treat illnesses caused by a disruption in programmed cell death. The fine balance between living and dying cells must be maintained a ....Throughout our lives cells must die and be replenished. One way multicellular organisms remove unwanted cells is through a process called programmed cell death. This process eliminates redundant, damaged or infected cells by a program of cell suicide. We are studying the underlying molecular mechanisms of this cell suicide in order to design new pharmaceuticals to treat illnesses caused by a disruption in programmed cell death. The fine balance between living and dying cells must be maintained and if this balance is lost then disease may result. A reduced level of cell death may result in cancers while too many dying can contribute to degenerative diseases such as Alzheimer's disease and stroke. Currently many of these diseases do not have effective treatments. We will determine the three-dimensional structures of key proteins involved in programmed cell death and use this information to design drugs that can interfere with the molecular processes involved in signalling cell death. Such drugs may prove useful new therapies in a wide range of diseases caused by a breakdown in the biochemical paths to cell death.Read moreRead less
Glycosyltransferase Effectors Of Enteropathogenic E. Coli And Salmonella
Funder
National Health and Medical Research Council
Funding Amount
$320,891.00
Summary
This project aims to characterise the mechanisms of disease caused by bacterial pathogens including Salmonella and enteropathogenic E. coli. These pathogens cause a significant amount of diarrhoeal disease and mortality worldwide particularly in infants and in countries where water sanitation is poor. I aim to investigate the specific mechanisms the bacteria employ to manipulate and avoid our immune response during infection in order to better understand and combat diarrhoeal disease.
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.
Assembly And Function Of Two Interacting Oncogenic Scaffolds
Funder
National Health and Medical Research Council
Funding Amount
$705,585.00
Summary
Aberrant signaling by the protein kinase superfamily is a known driving force for many cancers and inflammatory diseases. Recently, a subset of kinase-like proteins, termed pseudokinases, have emerged as crucial regulators of kinase signalling pathways. This proposal focuses on elucidating the scaffolding function and assembly of two pseudokinases, termed SgK223 and SgK269, which display oncogenic properties and aims to understand how their signalling abilities are subverted in a disease state.
Alzheimer’s disease (AD), is the most common form of dementia, accounting for between 50-70% of all cases. There is general agreement that current treatments for AD/dementia are inadequate so new treatment strategies are desperately needed. I am addressing these challenges by developing new technologies to generate next generation treatments for AD.
The Role Of Copper In Ubiquitin-dependent Protein Degradation In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$588,622.00
Summary
Ubiquitin’s are small proteins that tag other proteins in a process known as “Ubiquitination”. Often this is to target them for degradation once they are no longer needed i.e. to take out the rubbish. This process is disrupted in Alzheimer’s disease (AD), which may contribute to the disease. This project aims to find out if copper, an essential metal for life, is required for this process. Drugs that are designed to deliver copper to brain cells have been effective in small AD clinical trials.
The regulation of signalling molecules in Saccharomyces Cerevisiae by inositol polyphosphate 5-phosphatases. Phosphoinositide signalling molecules regulate the actin cytoskeleton, secretion, vesicular trafficking and cell growth and death. We have identified, cloned and characterised a family of signal terminating enzymes called inositol polyphosphate 5-phosphatases (5-phosphatases) that regulate phosphoinositide signalling molecules. We have cloned and characterised four distinct 5-phosphatases ....The regulation of signalling molecules in Saccharomyces Cerevisiae by inositol polyphosphate 5-phosphatases. Phosphoinositide signalling molecules regulate the actin cytoskeleton, secretion, vesicular trafficking and cell growth and death. We have identified, cloned and characterised a family of signal terminating enzymes called inositol polyphosphate 5-phosphatases (5-phosphatases) that regulate phosphoinositide signalling molecules. We have cloned and characterised four distinct 5-phosphatases in the yeast Saccharomyces Cerevisiae and demonstrated by both deletion and overexpression studies that these enzymes regulate the actin cytoskeleton, endocytosis and secretion. This research proposal aims to investigate the signalling complexes the 5-phosphatases form with specific actin binding and or regulatory proteins, investigate the complex interactions of phosphoinositide lipid phosphatases and the roles they play in regulating secretion from the endoplasmic reticulum and finally characterize a novel 5-phosphatase that we have recently identified. Collectively the outcome of these studies will provide novel information about the functionallly significant signalling pathways regulated by this important enzyme family.Read moreRead less
The role of PtdIns(4,5)P2 in cellular responses in Saccharomyces cerevisiae. This grant application falls under the criteria of frontier technologies in genomics/phenomics and complex systems. We are characterizing a highly conserved network of signaling molecules regulated by complex large families of enzymes that regulate the bending of membranes, and cellular events including cell division in plants, yeast and mammalian cells. We have developed cutting edge novel technologies to localize sign ....The role of PtdIns(4,5)P2 in cellular responses in Saccharomyces cerevisiae. This grant application falls under the criteria of frontier technologies in genomics/phenomics and complex systems. We are characterizing a highly conserved network of signaling molecules regulated by complex large families of enzymes that regulate the bending of membranes, and cellular events including cell division in plants, yeast and mammalian cells. We have developed cutting edge novel technologies to localize signaling on specific intracellular membranes and visualise the role cellular lipids play in forming tubules in cells. This project will result in the presentation of Australian research at international forums and support the training of PhD students.Read moreRead less