Unraveling The Dynamic Munc18a:Syntaxin1 Interaction Required For Neurotransmission
Funder
National Health and Medical Research Council
Funding Amount
$674,591.00
Summary
Membrane trafficking, the topic of the 2013 Nobel prize in Medicine, is required for delivery of cellular cargo. This research will investigate the interactions and structures of proteins from the neuronal membrane trafficking system. Understanding how this system operates will expand our knowledge of processes fundamental to learning and memory and may ultimately lead to development of selective therapeutics for treating a range of diseases.
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.
Characterization Of The Type IX Secretion System In Porphyromonas Gingivalis
Funder
National Health and Medical Research Council
Funding Amount
$831,656.00
Summary
Periodontitis is associated with the keystone pathogen Porphyromonas gingivalis. We have identified a novel protein secretion machine comprised of at least 12 components in P. gingivalis which transports the bacterium's major virulence factors to the cell surface and attaches them to the outer membrane. We aim to determine the spatial arrangement and specific role of each of these 12 components and thereby provide targets for future treatments against this disease.
Function And Molecular Mechanism Of Histidine-rich Glycoprotein In Necrotic Cell And Pathogen Clearance
Funder
National Health and Medical Research Council
Funding Amount
$525,957.00
Summary
This research proposal is to investigate the molecular mechanism and function of a blood serum protein, histidine-rich glycoprotein (HRG), in protecting against tissue injury caused by inflammation and infection. HRG has been implicated in controlling important aspects of tissue injury by aiding removal of dead cells and pathogens. Understanding the role of HRG in these disease settings may allow the development of approaches for the treatment of inflammatory, autoimmune and infectious disease.
Coupling The Cell Cortex To Membranes: Structural Basis For The Activation And Control Of Ezrin
Funder
National Health and Medical Research Council
Funding Amount
$587,548.00
Summary
Cells are dynamic: they change shape, communicate with each other and import/export signalling molecules. These dynamic processes are controlled via the interaction of the cell membrane with the underlying actin cytoskeleton and they are important for health, for example, they are critical for proper immune cell function. The goal of this project in to unravel the control of membrane dynamics by defining the interactions between the cell membrane and the proteins: ezrin and RhoA.
How Do BET Bromodomain Proteins Regulate Gene Expression?
Funder
National Health and Medical Research Council
Funding Amount
$586,791.00
Summary
This project is aimed at defining the biochemical mechanisms of action of a class of gene regulatory proteins (BET proteins) that are currently considered to be exciting drug targets for a range of diseases, predominantly cancer. A better understanding of the means by which BET proteins regulate gene expression will be important for the rational design and application of drugs that selectively target the proteins.
Endosomal Sorting Of Amyloid Precursor Protein In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$858,643.00
Summary
Alzheimer's Disease is a progressive neurological disorder and is the most common cause of dementia. Effective treatments are desperately needed, but none are currently available. The toxic amyloid peptide A? is central to disease pathology and is derived from breakdown of the Alzheimer’s amyloid precursor protein (APP). In this project we will examine the interactions between APP and the molecular machinery that controls its location in the cell and subsequent degradation.
Biochemical Reconstitution Of The Ubiquitin Ligase Pathway Defective In Fanconi Anaemia
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
Fanconi Anemia (FA) is characterised by loss of vital blood cells but also 700x risk of developing leukaemia and other cancers. FA is caused by an inherited defect in one of 15 different genes that provide a signal and repair mechanism protecting cells from cancer causing mutations. By reconstructing this signaling mechanism in the test tube we will determine how it contributes to cancer protection, and highlight potential strategies for treatment of FA and leukaemia in the general population.
SULT4A1 is not a sulfotransferase, but a sulfotransferase inhibitor. It forms high affinity heterodimers with other sulfotransferases via a conserved dimerisation site in its carboxyl terminus attenuating catalytic activity. Consequently, it is important for the metabolism of numerous important molecules including estrogens, thyroid hormones, neurotransmitters and many therapeutic agents.
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.