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Understanding Cell Signalling As A Basis For New Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$863,910.00
Summary
This fellowship will capitalise on my extensive expertise in determining the three-dimensional atomic structures of proteins to uncover fundamental biological mechanisms in cancer and Alzheimer’s disease as a basis for discovering new drugs to combat these devastating diseases.
Life needs energy. We breathe and eat to make the universal biological fuel adenosine triphosphate (ATP). We turn over our own body weight in ATP every day and imbalances in this process lead to severe disorders such as obesity, diabetes and heart disease as well as to ageing. For any real breakthroughs we need to understand the machinery behind biological energy conversion in molecular detail and this is what my laboratory is aiming to achieve.
My research is aimed at understanding how the structure and dynamics of proteins dictates their function. I use X-ray crystallography to determine the shapes of proteins. Proteins are not static, however - they move in complicated ways, and often their motion is critical to their function (molecular motors, for example). It is very difficult to 'watch' this movement in the lab, so I use computer simulation to try to understand how proteins move.
The blood system is made up of different types of blood cells (red cells, white cells, platelets etc). The correct number of each type of cell is controlled by chemical messengers called cytokines. Because overactive cytokine signalling can lead to inflammatory disease and leukemia it is tightly controlled by the other molecules in the body. This project aims to determine the exact mechanism whereby this is achieved with the aim of developing therapies to treat inflammatory disease and leukemia.
Structural Studies Of The Molecular Machinery Regulating Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$638,517.00
Summary
Our bodies use a process called Programmed Cell Death to remove unwanted or dangerous cells. This work aims to understand the machinery that regulates this process at the molecular level. These insights will inform the development of drugs aimed at either initiating cell death when required, for example in cancer, or at inhibiting it when excessive cell death causes disease.
Integrated Approaches To Targeting G Protein-coupled Receptors: Translational Studies Of Novel Drug-receptor Paradigms
Funder
National Health and Medical Research Council
Funding Amount
$851,980.00
Summary
This Fellowship focuses on one of the largest family of proteins found in the human body, the so-called ‘G protein-coupled receptors ‘ (GPCRs). GPCRs control how each of our cells communicates with one another, and have been implicated in virtually all diseases. This proposal will study new mechanisms of targeting drugs to GPCRs that can overcome current drug discovery bottlenecks and lead to new ways of treating neuropsychiatric, cardiovascular, inflammatory and metabolic diseases.
Development Of Membrane Protein Structural Biology In Australia
Funder
National Health and Medical Research Council
Funding Amount
$601,484.00
Summary
Membrane proteins are key components of all living organisms, constituting more than 30% of cellular proteins and representing more than 50% of all drug targets. Despite their medical importance our knowledge of membrane proteins is still extremely limited and requires further technological advances. This work will firmly establish membrane protein crystallography in Australia and provide a basis for training of new researchers in this important field.
Structure-based And Fragment-based Approaches To Developing New Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$763,409.00
Summary
Two powerful and complementary approaches to developing new drugs will be combined to target proteins that play key roles in malaria and other parasite and bacterial infections with the aim of developing new therapeutics. In addition, the potential of peptide toxins to treat autoimmune diseases such as multiple sclerosis, as well as chronic pain and other conditions, will be exploited to develop new drugs.