Redox Control Of The Immune Regulatory Protein, Indoleamine 2,3-dioxygenase
Funder
National Health and Medical Research Council
Funding Amount
$576,538.00
Summary
An enzyme called indoleamine 2,3-dioxygenase is important for controlling the immune system during normal and disease conditions including pregnancy, cancer, inflammation and infectious disease. Despite its importance little is known about how this enzyme is controlled. This project will provide important new insights into how this enzyme is regulated. Such fundamental scientific information can discover new ways in which to alter the enzyme's activity in order to modulate immune responses.
The dramatic increase in obesity and age-related metabolic disorders demonstrates the importance of gaining a better understanding of how cells and organisms regulate their energy stores. This project will identify novel molecular mechanisms that control the enzyme CaMKK2, which is a key regulator of whole-body energy metabolism. This will provide new opportunities to inform more effective strategies to tackle metabolic diseases, and improve health in an increasingly ageing population.
Charting The Interface Between Cellular Metabolic States And Gene Regulation
Funder
National Health and Medical Research Council
Funding Amount
$653,196.00
Summary
The research successes of Molecular Biology and Biochemistry have given us detailed pictures of the regulatory and metabolic states of cells and tissues, yet we know little about how these states affect each other. We hypothesise the existence of regulatory interactions between ribonucleic acids, enzymes and metabolites to connect gene expression and metabolism. We will employ novel RNA Biology methods to discover such regulatory interactions in medically important cellular contexts.
Targetting The CIB1-sphingosine Kinase Interaction In Oncogenesis
Funder
National Health and Medical Research Council
Funding Amount
$805,034.00
Summary
Sphingosine kinase is a protein involved in cancer development and progression. We have identified that the cancer-inducing activity of sphingosine kinase is controlled by another protein called CIB1 which itself appears involved in causing cancer by deregulating sphingosine kinase. In this study we will examine and target the interaction between sphingosine kinase and CIB1 as a potential therapeutic intervention in cancer.
Preventing The Evolution Of Transmissible Nitroimidazole Resistance In Mycobacterium Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$664,463.00
Summary
Tuberculosis kills more people than any other infectious disease. Unfortunately, the drugs available to us to treat TB are losing their efficacy due to the evolution of drug resistance. A new class of drugs, nitroimidazoles, has been developed, but there is a risk that the bacterium that causes TB will develop resistance to these compounds too. We will identify resistance mutations before they occur in the wild, to help identify them and find new compounds for which resistance cannot develop.
DsbA Foldases From Multidrug Resistant Pathogens As Targets For New Antimicrobials
Funder
National Health and Medical Research Council
Funding Amount
$743,401.00
Summary
Bacteria that cause common human infections, such as cystitis and diarrhoea, are now resistant to many antibiotics. If no action is taken, by 2050 antibiotic resistant infections will kill more people each year than cancer. This project aims to address this global public health crisis by characterising promising new bacterial targets and inhibitors designed to disarm multidrug resistant pathogens. Longer term this work could provide new infection therapies that are urgently needed.
Dissecting The Pathogenic Triad Of Enteric Pathogens: Assembly, Structure And Function Of Autotransporter Proteases
Funder
National Health and Medical Research Council
Funding Amount
$639,428.00
Summary
SPATEs are proteases secreted by many enteric bacteria that contribute to their pathogenic potential by damaging host tissues and evading the host immune response. We aim to study the structural basis of their assembly and biological function. The information we gain will assist the development of new diagnostics and improved therapies for enteric infections.
The Molecular Basis Of Cytochrome P450 Ligand Binding: Towards Predicting Enzyme Substrate Selectivity And Drug-drug Interaction Potential
Funder
National Health and Medical Research Council
Funding Amount
$558,447.00
Summary
Cytochrome P450 (CYP) enzymes play a pivotal role in the metabolism (i.e. chemical breakdown) of drugs, a process that is essential for their detoxification and elimination from the body. This project will combine advanced computational and experimental approaches to elucidate the molecular basis for the binding of drugs to CYP enzymes, which is crucial for the design of drugs with favourable metabolic properties and decreased propensity for harmful interactions with co-administered drugs.
Novel TB Drug Candidates Via The Inhibition Of Lipid I Biosynthesis
Funder
National Health and Medical Research Council
Funding Amount
$780,743.00
Summary
Tuberculosis (TB) is an enormous global health problem with a continuing impact in Australia. TB is now the leading killer of any infectious disease (1.8 million people per year) and the rapid emergence of drug resistant TB infections threatens to prevent efforts to control the disease. This project seeks to develop novel TB drug candidates that operate by preventing the construction of the cell wall by the bacterial agent that causes the disease.
Biochemical Investigation Of Ubiquitination By The Fanconi Anaemia Pathway
Funder
National Health and Medical Research Council
Funding Amount
$603,447.00
Summary
Fanconi anaemia is an inherited disorder with greatly elevated risk of leukaemia and cancers. The causal genes are ‘tumour suppressors’ that protect us from cancer by a complex function in repair of damage to our DNA. This study aims to understand how this DNA repair function protects us from cancer, and may influence some forms of new forms of cancer treatment.