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.
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.
Structure, Function And Dynamics Of ATP Synthases And Rotary Proton Pumps
Funder
National Health and Medical Research Council
Funding Amount
$923,020.00
Summary
ATP synthase is the molecular machinery that converts energy derived from nutrients or photosynthesis into the universal biological fuel source ATP (adenosine triphosphate). This is one of the most fundamental processes of life and is conserved from bacteria to plants to humans. Understanding how ATP synthase and its relatives work in molecular detail is expected to have wide-ranging implications for both medicine (in understanding metabolic disorders) and the design of new antibacterial agents.
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.
Molecular Basis For Stress-induced Gene Regulation—a Model System To Understand Transcriptional Deregulation In Cancer And Neurological Disease
Funder
National Health and Medical Research Council
Funding Amount
$384,076.00
Summary
Deregulated gene transcription plays a critical role in cancer formation. It is therefore important to understand the molecular basis of gene transcription and how tumour cells hijack the process. In this Project, we will study the molecular basis of stress-inducible gene expression. This is particularly important for understanding the molecular basis of cancer as stress-inducible genes are activated by transcription factors implicated in breast, colon, lung, and prostate cancers.
Structural Characterisation Of The Co-inhibitory Complex Formed By The Tumour Suppressor PTEN And The Metastatic Factor PREX2
Funder
National Health and Medical Research Council
Funding Amount
$563,602.00
Summary
Metastasis is a major cause of cancer mortality. Characterisation of key proteins that regulate metastasis is therefore a priority. PTEN and PREX2 are enzymes that play key roles in metastasis in melanoma, and other cancers. We will determine the structural basis of PTEN:PREX2 co-inhibition, and determine how cancer-associated PREX2 mutations dysregulate this inhibitory complex. This study will provide the necessary knowledge for future drug development programs targeting PTEN:PREX2 in cancer.
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.
Structural And Functional Characterisation Of The Oncogene P-Rex1
Funder
National Health and Medical Research Council
Funding Amount
$623,447.00
Summary
The spread of cancer to other parts of the body (metastasis) is a major cause of mortality. The characterisation of proteins that regulate metastasis is therefore a priority. P-Rex1 plays a crucial role in promoting metastasis in breast and other cancers. We will determine the structural basis of P-Rex1 activity, and investigate how its dysregulation promotes aberrant cell growth. This study will provide the knowledge to build future drug development programs targeting P-Rex1 in cancer.
Structural Characterisation Of Long Non-Coding RNA Bound Histone Modification Complexes
Funder
National Health and Medical Research Council
Funding Amount
$320,891.00
Summary
Cancer is a disease associated with genetic and epigenetic changes of DNA. Epigenetics involves external changes to the DNA, switching processes “on” and “off”, to regulate gene expression. This project aims to provide powerful insight into key processes involved in epigenetic-based carcinogenesis, and thereby lay the foundation for producing novel cancer diagnostic markers and molecular based therapies.
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.