Development Of Resonance Energy Transfer Technologies To Detect GPCR Heterodimer Complexes In Living Cells
Funder
National Health and Medical Research Council
Funding Amount
$205,555.00
Summary
G-protein coupled receptors are proteins at the surface of most cells in the body. They bind to drugs, transmitting signals into cells that change what cells are doing. Recent research indicates that different types of these proteins can interact with each other and when one of these protein combinations binds a drug, it acts differently to when the proteins act separately. The aim of our project is to find out which protein combinations exist and to find drugs that bind to them specifically.
Discovery And Mechanisms Of Host Cell Factors In HIV Uncoating
Funder
National Health and Medical Research Council
Funding Amount
$635,098.00
Summary
HIV entry into the host cell involves release of its capsid, a protein shell protecting the viral genome. The capsid hijacks host proteins to cloak itself from cellular defenses while the cell has evolved sensors that can block viral infection. This proposal aims to discover proteins involved in this arms race between host and virus and decipher how they control capsid disassembly. This insight will help design new drugs against HIV infection and new ways to deliver genes for gene therapies.
Structural And Drug Discovery Studies Of Medically Important Protein Complexes
Funder
National Health and Medical Research Council
Funding Amount
$438,577.00
Summary
My research is focused on structural studies of medically important biological systems, where specific protein complex formation contributes to human illnesses. I use X-ray crystallography to visualize the whole complex at atomic resolution as well as to determine whether binding partners have undergone changes in shape upon complex formation. This structural information then helps me in drug design with goals to either disrupt or modulate the complex.
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.
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.
Structure Determination Of Fms And Kit Kinases And Their Inhibtors For Directed Drug Design
Funder
National Health and Medical Research Council
Funding Amount
$373,250.00
Summary
Tyrosine kinases are a large and important family of enzymes that play a fundamental role in the control and communication between cells. When damaged or uncontrolled, these enzymes can contribute to the development of diseases such as cancer and immune related disorders. This proposal aims to develop therapeutics targeted at the tyrosine kinases using a combination of the Structure Biology expertise at Monash University and the drug discovery platform technologies of Cytopia Pty Ltd. Promising ....Tyrosine kinases are a large and important family of enzymes that play a fundamental role in the control and communication between cells. When damaged or uncontrolled, these enzymes can contribute to the development of diseases such as cancer and immune related disorders. This proposal aims to develop therapeutics targeted at the tyrosine kinases using a combination of the Structure Biology expertise at Monash University and the drug discovery platform technologies of Cytopia Pty Ltd. Promising drug candidates already identified by Cytopia will be analysed at their site of action using X-ray crystallography. This information will enable a rational process of modification and improvement of the candidate drugs. The development of a range of therapeutics for Phase I clinical trials will be of enormous benefit to Australia�s medical industry and pubic health.Read moreRead less
Structure Based Drug Design Of Inhibitors Of The Cholesterol-dependent Cytolysins And Respiratory Syncytial Virus Fusion
Funder
National Health and Medical Research Council
Funding Amount
$377,039.00
Summary
The aim of this work is to determine the three-dimensional atomic structures of proteins that play a role in infection by human pathogens. The structures will provide the basis for developing compounds that interfere with the function of these proteins and hence have potential as drugs to fight infection. The proteins being studied are required for the invasion of human tissues by pathogens; one group are toxins produced in bacterial infections such as pneumonia and meningitis while the other pr ....The aim of this work is to determine the three-dimensional atomic structures of proteins that play a role in infection by human pathogens. The structures will provide the basis for developing compounds that interfere with the function of these proteins and hence have potential as drugs to fight infection. The proteins being studied are required for the invasion of human tissues by pathogens; one group are toxins produced in bacterial infections such as pneumonia and meningitis while the other proteins to be studied are used by viruses to infect human cells.Read moreRead less
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.