Structure And Function Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$1,282,475.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
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.
The Structural Basis For Glutamate Transporter Function
Funder
National Health and Medical Research Council
Funding Amount
$373,144.00
Summary
Glutamate transporters are vacuum cleaners in the brain that suck the neurotransmitter glutamate into cells. When the glutamate vacuum breaks down or becomes blocked, glutamate levels outside cells increase, leading to cell death in the brain. This process underlies the damage in many brain diseases including Alzheimer’s disease and stroke. The aim of this project is to understand the mechanism of the glutamate vacuum cleaner so we can develop therapeutics to fix it when it breaks down.
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
Assembly And Misassembly Of Mitochondrial Respiratory Chain Complex I
Funder
National Health and Medical Research Council
Funding Amount
$520,520.00
Summary
Mitochondria are the powerhouses in our cells. They burn the carbon fuels we eat and store the energy by making ATP that is used for functions such as muscle contraction and triggering of nerves. Mitochondrial Complex I is a molecular motor that helps to make ATP. “Mitochondrial disease” is often seen when Complex I is not built properly and this results in early childhood death. In this project we will study how Complex I is built and how the mitochondria responds to assembly problems.
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.
Functional And Molecular Characterization Of A Novel Regulator Of Angiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$474,907.00
Summary
All cells in the body require blood vessels for the provision of nutrients and waste-removal. A deficiency of vessels prevents proper healing whereas an overabundance is a hallmark of diseases such as cancer and macular degeneration. This research will investigate a novel gene that is essential for new vessel growth. The project aims to understand the mechanism of how this gene functions. Ultimately, the research aims to inform therapeutic development for stimulating or inhibiting vessel growth.
Investigating The Interaction Of Precursor Inner Membrane Proteins With Translocase Components
Funder
National Health and Medical Research Council
Funding Amount
$585,274.00
Summary
Proteins are synthesised on ribosomes located in the cellular plasm, and then moved to their site of action by specialised transport systems. Import of proteins to the mitochondria involves translocase pores, which come equipped with receptors and chaperones. We are investigating the targeting and transfer of newly synthesised proteins of the MCF carrier family from the ribosomal machinery to the inner mitochondrial membrane, focusing on interaction with chaperones in the intermembrane space.
Discovery And Characterisation Of Novel Tick Evasins As Inhibitors Of Chemokine-mediated Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$654,847.00
Summary
An important aspect of inflammatory diseases is the migration of white blood cells into the affected tissues. This is controlled by a group of proteins called chemokines. Ticks, which live on mammalian hosts, produce proteins called evasins, which interact with host chemokines and thereby prevent inflammatory responses. This project will discover new tick evasins, study their chemokine interactions and investigate their ability to block inflammation in allergic asthma.
Imaging The Machinery Of Bacterial Locomotion At Atomic Resolution
Funder
National Health and Medical Research Council
Funding Amount
$360,732.00
Summary
Our aim is to a) understand and b) sabotage the machinery of locomotion in bacteria. The flagellar motor propels bacteria at 100s of revolutions per second through viscous media making this the most powerful motor known to man. Bacteria can sense their environment and make informed decisions to avoid hazards or find food. Understanding how this machinery works in atomic detail is expected to have implications for both the development of new antibacterials and in the area of nano-medicine.