The Molecular Basis For Manganese Uptake By Pathogenic Bacteria.
Funder
National Health and Medical Research Council
Funding Amount
$632,949.00
Summary
Bacterial antimicrobial resistance is an increasing threat to human health. At this point in time, there is an urgent, fundamental need for the development of new antimicrobial strategies. Bacterial infection involves a constant tug-of-war between the pathogen and the human host for the essential nutrients of life, including trace metal nutrients such as Mn. This project seeks to understand the machinery for Mn uptake by pathogenic bacteria as a target for novel antibacterial design.
STRUCTURE, FUNCTION AND REGULATION OF F-TYPE ATP SYNTHASES
Funder
National Health and Medical Research Council
Funding Amount
$544,660.00
Summary
ATP synthase is the molecular machinery that converts energy derived from nutrients or photosynthesis into the universal biological energy carrier ATP (adenosine triphosphate). This is one of the most fundamental processes of life and is conserved from bacteria to plants to humans. Understanding how bacterial and mitochondrial ATP synthases work in molecular detail will have wide-ranging implications for both medicine (in understanding metabolic disorders, controlled cell death and aging) and th ....ATP synthase is the molecular machinery that converts energy derived from nutrients or photosynthesis into the universal biological energy carrier ATP (adenosine triphosphate). This is one of the most fundamental processes of life and is conserved from bacteria to plants to humans. Understanding how bacterial and mitochondrial ATP synthases work in molecular detail will have wide-ranging implications for both medicine (in understanding metabolic disorders, controlled cell death and aging) and the design of new antibacterial agents.Read moreRead less
Peripheral Membrane Proteins In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$469,151.00
Summary
Peripheral membrane proteins are critical for processes such as cell transport, signaling, neurosecretion and development. As such, their dysfunction can lead to many debilitating diseases including cancer, inflammation and neurodegeneration. This project will establish fundamental new knowledge about how peripheral membrane proteins regulate cell function, how their perturbation or mutation results in human disease, and will inform efforts to target them for future therapeutic outcomes.
A Targeted Nutrient-depletion Approach To Tackle Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
Prostate cancer is the most prevalent male specific cancer, and has a similar incidence to breast cancer in women. We are studying the role of protein pumps that control the amount of nutrients taken into and out of cancer cells. We are aiming to structurally determine LAT1 and LAT3, two nutrient pumps important for cancer progression, and to use these structures as a platform for drug design where the intention is to drugs 'starve’ the cancer by restricting nutrient uptake.
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.
Determining The Molecular Basis Of Tumour Cell Multidrug Resistance: Structural And Functional Analysis Of Breast Cancer Resistance Protein
Funder
National Health and Medical Research Council
Funding Amount
$325,396.00
Summary
Around 40% of human tumours develop resistance to chemotherapeutic drugs; a trait most commonly acquired by the increased expression of membrane proteins that remove a broad spectrum of molecules from the cell. This project aims to determine the structure of the human breast cancer resistance protein (BCRP), a protein of particular importance in this process. The structure of BCRP will provide a scaffold for the design of drugs aimed at inhibiting chemotherapy drug resistance.
The Molecular Basis Of G Protein Coupled Transport
Funder
National Health and Medical Research Council
Funding Amount
$495,938.00
Summary
G proteins are molecular switches in all organisms, turning fundamental processes on and off . Defects in the functions of these switches can lead to severe diseases, such as cancer. Crucial details regarding the mechanism by which these switches are turned to on are still missing. This proposal will use a bacterial model system, with aims to provide structural and functional detail on the molecular mechanism of the switch in G proteins, and to extend this model to mammalian systems.
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.
Antibiotic resistant bacteria cause life-threatening diseases and represent a major public health problem. Globally, drug-resistant infections currently cause over 500,000 deaths annually and this figure is projected to exceed 10 million by 2050. Venom peptides are a new avenue of antibiotic discovery. This proposal aims to define how these peptides interact with the cellular power generator, ATP synthase, to provide a basis for exploiting their potential to treat bacterial infections.
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.