Targeting TRPV4 Activation Mechanisms To Reveal Novel Pain Therapies
Funder
National Health and Medical Research Council
Funding Amount
$580,938.00
Summary
Pain nerves sense painful chemical and physical stimuli, by opening protein "ion channels" which let small electric currents traverse the cell membrane. This pain signal is transmitted to the spinal cord and then the brain, where it is perceived as pain and elicits a reaction. But we don't know how the ion channels open. This project will investigate how receptors for painful substances open ion channels to cause pain. Understanding this mechanism will help us to make new drugs to treat pain.
Legionella bacteria are the major cause of Legionnaire’s Disease, a common form of acute pneumonia. Here we will study how the bacteria avoid killing in human cells by establishing an intracellular niche that is sequestered from the normal host cell defence pathways. In particular we hope to understand how the bacteria regulate a major protein modification pathway called ubiquitination.
Role Of The Microglial Adaptor Molecule TYROBP In Alzheimer’s Disease Pathology
Funder
National Health and Medical Research Council
Funding Amount
$469,433.00
Summary
Immune activation characterizes Alzheimer’s disease (AD) brains; however, how it impacts AD progression is not understood. Our previous studies in AD brains identified the immune molecule TYROBP, pointing at both beneficial and detrimental effects triggered by this molecule. Here, we aim to understand in detail how TYROBP is involved in AD and how we can enhance its beneficial effects and decrease its unintended actions.
Elucidating The Role Of Epididymosomes In The Transfer Of Fertility-modulating Proteins And Regulatory Classes Of RNA To Maturing Spermatozoa
Funder
National Health and Medical Research Council
Funding Amount
$539,425.00
Summary
Sperm dysfunction represents a major underlying aetiology associated with male infertility. This proposal seeks to understand the mechanisms responsible for driving the functional maturation of spermatozoa and how these mechanisms are perturbed in response to environmental stressors.
Interferon Mediated Control Of Legionella Infection
Funder
National Health and Medical Research Council
Funding Amount
$628,848.00
Summary
Bacterial lung infections are a serious cause of illness and death in humans. To fight infection the body activates the immune system using a network of signalling molecules. We are studying exactly how one of these signalling molecules called interferon controls the infection. Interferon induces the killing of bacteria that are replicating inside human lung cells. How interferon drives bacterial death is not known and this will be studied in this proposal.
Manipulation Of Clathrin-mediated Trafficking By Coxiella
Funder
National Health and Medical Research Council
Funding Amount
$667,857.00
Summary
This research will uncover how Coxiella causes the serious infectious disease Q fever by commandeering human cells and replicating to high numbers within a specialised vacuole. We will investigate virulence factors of Coxiella, learning how and why they target an essential human vesicular trafficking process. Our innovative approach and unique expertise will elucidate interaction between this pathogen and the human cell, providing fundamental knowledge towards public health outcomes.
Phosphoinositide 3-kinase Signalling And Skeletal Muscle Mass.
Funder
National Health and Medical Research Council
Funding Amount
$597,598.00
Summary
Maintenance of skeletal muscle mass is essential for human health and locomotion. In ageing and cancer, loss of muscle mass leads to severe weakness and immobilization causing morbidity and mortality. This grant aims to characterise a novel gene that when deleted in mice leads to significant muscle damage. The molecular pathways within the cell that lead to the observed muscle damage will be investigated and this may provide insights into the pathways that control muscle damage and its regenerat ....Maintenance of skeletal muscle mass is essential for human health and locomotion. In ageing and cancer, loss of muscle mass leads to severe weakness and immobilization causing morbidity and mortality. This grant aims to characterise a novel gene that when deleted in mice leads to significant muscle damage. The molecular pathways within the cell that lead to the observed muscle damage will be investigated and this may provide insights into the pathways that control muscle damage and its regenerationRead moreRead less
Many of the most serious diseases of Western societies including obesity, Type 2 diabetes, cancer growth and metastasis and cardiovascular disease have metabolic dimensions. The enzyme AMPK regulates cellular and whole body energy homeostasis by coordinating metabolic pathways to balance energy demand with nutrient supply. We are studying the structure and function of AMPK with the aim of better treating metabolic diseases.
How The Intracellular Pathogen Coxiella Burnetii Manipulates Host Small GTPases To Facilitate Disease
Funder
National Health and Medical Research Council
Funding Amount
$534,510.00
Summary
This study explores how the bacterium Coxiella burnetii causes the serious infectious disease Q fever. Coxiella is a potential biological weapon because it is stable in the environment and few organisms are required to cause disease. Coxiella is able to manipulate human cells to replicate in a unique location within the cell but little is known about how they do this. Here we will study the host proteins that are important during infection and how Coxiella manipulates these factors to facilitate ....This study explores how the bacterium Coxiella burnetii causes the serious infectious disease Q fever. Coxiella is a potential biological weapon because it is stable in the environment and few organisms are required to cause disease. Coxiella is able to manipulate human cells to replicate in a unique location within the cell but little is known about how they do this. Here we will study the host proteins that are important during infection and how Coxiella manipulates these factors to facilitate intracellular replication.Read moreRead less
Defining Pathogenic Mechanisms Of Intracellular Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$494,691.00
Summary
This study explores how the bacterium Coxiella burnetii causes the serious infectious disease Q fever. Coxiella is a potential biological weapon because it is very stable in the environment and few organisms are required to cause disease. Coxiella is able to commandeer human cells to replicate in a specialized vacuole but little is understood about how they do this. We will examine the virulence factors of Coxiella and investigate how they allow the bacteria to replicate inside human cells.