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.
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.
Peptide Toxins From Animal Venoms Specifically Targeting Voltage-gated Sodium Channels As Novel Analgesics And Pesticides
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
This project aims to understand how certain animal toxins that cause analgesic and pesticidal effects in model animals interact with biological ion channels in atomistic detail using computational techniques. By understanding the detailed molecular interactions involved in the binding of the toxins to channels, toxin variants with improved potency and specificity may be designed as promising templates for novel analgesics and pesticides.
The Proteomics Of The Von Hippel-Lindau (VHL) Tumour Suppressor Protein
Funder
National Health and Medical Research Council
Funding Amount
$292,639.00
Summary
This project primarily intends to identify novel modifications to the von Hippel-Lindau (VHL) protein which plays a role in tumour suppression and blood vessel growth. It is the purpose of this project to characterise these changes to VHL and ultimately, understand what these changes mean to the function of VHL protein, and modulate them to ameliorate VHL disease.
Recent evidence suggests that the Siah proteins are involved in sensing low oxygen levels in cells, and subsequently activating processes to help the cell survive under these conditions. Low oxygen conditions occur in cancer and sites of inflammation, suggesting that inhibiting Siah may improve patient outcomes in diseases such as cancer and arthritis. We aim to perform a high throughput screen for drugs that inhibit Siah protein function and to test these in cancer cells.
Structural Characterisation Of SNARE Protein Complexes Involved In Insulin-regulated Glucose Transport
Funder
National Health and Medical Research Council
Funding Amount
$320,803.00
Summary
Insulin-regulated glucose transportation is defective in type 2 diabetes, a disease that is a major health problem worldwide and in some cases can lead to death. The aim of this work is to investigate the molecular structure and function of proteins critical to the transportation and delivery of glucose to muscle and fat cells, which will lead to the validation of new therapeutic targets and the development of new treatments for diabetes.