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Circuit Breaker: Investigating The Regulatory Circuits Controlling Expression Of Drug Efflux Pumps In The Nosocomial Pathogen Acinetobacter Baumannii
Funder
National Health and Medical Research Council
Funding Amount
$515,244.00
Summary
Hospital-acquired infections caused by drug resistant pathogenic bacteria cost billions of dollars and increase patient pain and morbidity. This research will study the genes controlling multidrug efflux pumps in a major hospital-acquired bacterial pathogen, Acinetobacter baumannii. These efflux pumps make the bacteria resistant to antimicrobials by pumping them out of the cell. The results will allow us to better track drug resistant strains and will inform treatment options.
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.
Membrane Trafficking Of BACE1 And Amyloid Precursor Protein In Primary Neurons And The Production Of Abeta Amyloid Peptides
Funder
National Health and Medical Research Council
Funding Amount
$705,984.00
Summary
The development of Alzheimer’s disease results from the generation of toxic peptides by the cleavage of a membrane protein by an enzyme called BACE. A key feature of which regulates the generation of toxic peptides involves the movement of BACE between compartments in the cell by a process known as membrane transport. Our recent work has identified the itinerary of BACE in the cell. The studies here will reveal the molecular machinery of the BACE pathway in neurons. This fundamental informati
Membrane Trafficking Of The ?-secretase, BACE1, And The Generation Of Alzheimer's Disease A? Amyloid Peptides
Funder
National Health and Medical Research Council
Funding Amount
$465,704.00
Summary
Alzheimer’s disease results from the production of toxic neuropeptides by the action of an enzyme called BACE. The generation of toxic peptides requires the movement or trafficking of BACE between different cell compartments. This research will reveal the molecular machinery of the BACE transport pathway. This new knowledge will provide a strategy to develop drugs to inhibit BACE activity and the production of the toxic peptide, which would be of significant benefit to patients and families.
Dissecting A Serial Killer: Investigating The Degranulation Pathways In Cytotoxic Lymphocytes
Funder
National Health and Medical Research Council
Funding Amount
$604,459.00
Summary
When cells of the human body become cancerous or infected with virus, the body's immune system engages cytotoxic lymphocytes, known as "killer cells", that secrete an auxiliary of toxic proteins to eliminate these cells. The aim of this study is to investigate the mechanisms by which these critical immune cells accomplish this task. Importantly, humans who are genetically lacking in critical constituents of the cytotoxic lymphocyte are less able to fight off a viral infection and may be at a hig ....When cells of the human body become cancerous or infected with virus, the body's immune system engages cytotoxic lymphocytes, known as "killer cells", that secrete an auxiliary of toxic proteins to eliminate these cells. The aim of this study is to investigate the mechanisms by which these critical immune cells accomplish this task. Importantly, humans who are genetically lacking in critical constituents of the cytotoxic lymphocyte are less able to fight off a viral infection and may be at a higher risk of developing cancer.Read moreRead less
The proposed research project involves a fundamental biochemical and biophysical investigation of a protein (ABCA4) intimately involved in the visual process. The precise role of ABCA4 in vision has not yet been elucidated, although evidence suggests a role as a lipid translocase in the retinal regenerative pathway. Our primary objective is to provide direct evidence for this putative role.
Determining Fundamental Mechanisms Compromised In Kir-linked Disease States
Funder
National Health and Medical Research Council
Funding Amount
$600,040.00
Summary
The human nervous system and organs are reliant on precisely controlled transmission of electrical currents through sodium and potassium channels. Their core functions are compromised when currents fail to switch on and off normally. Faulty potassium channels are implicated in diabetes, epilepsy and heart failure. This project re-examines the mechanisms controlling potassium channels, with a view to scientific and therapeutic discrimination between the different classes present in human cells.
Exploring The Role Of Arrcd4 In Extracellular Vesicle Biogenesis And Its Implications In Tissue Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$678,742.00
Summary
Most cells in the body release small packages known as extracellular vesicles (or EVs in short), which carry proteins and other cellular material. EVs transport important cellular messages required for the everyday function of cells and play crucial roles both in normal wellbeing and disease. This proposal will investigate how EVs are formed, how they select their protein content and how they contribute to the maturation of some cell types in the body.
Novel Insights Into The Molecular Mechanisms Of Manganese Recognition And Acquisition By Pathogenic Bacteria.
Funder
National Health and Medical Research Council
Funding Amount
$843,035.00
Summary
Streptococcus pneumoniae is the world’s foremost bacterial pathogen. In Australia, bacterial infections are responsible for more than 9000 deaths every year, and the economic burden associated with treating diseases arising from pneumococcal infections is more than $4 billion annually. This proposal aims to define the molecular basis of how bacteria scavenge manganese from the host environment. This knowledge will provide the foundation for next generation antimicrobial therapeutics.
Modifying Brain Excitabilty By Upregulating The KCC2 Chloride Transporter
Funder
National Health and Medical Research Council
Funding Amount
$535,662.00
Summary
Brain activity depends upon the fine balance between neuronal excitation and inhibition. When this balance is lost, debilitating seizures can result, such as occurs in epilepsy. We have developed a new gene manipulation approach to enhance neuronal inhibition and prevent seizures in mice. We will examine the physiological mechanisms underlying this effect, and we propose that we can also use this genetic switch to stop the progression into epilepsy that occurs following a brain trauma.