Chronic Lymphocytic Leukemia (CLL) is a very common blood cancer. Leukaemic tumour cells actively shut down key immune defences in patients who are very prone to severe infections. Current chemotherapies further immuno-compromise CLL patients and over a quarter will die from an infection despite having responded to cancer treatments. We propose that restoring key immune functions in CLL is key to improve resistance to infection and restore natural anti-cancer immunity.
Exploiting The Cross Talk Between Tuft Cells And Group 2 Innate Lymphoid Cells For Tissue Homeostasis And Disease
Funder
National Health and Medical Research Council
Funding Amount
$831,162.00
Summary
The project investigates the cellular cross talk within the gastric mucosa between tuft cells, a rare epithelial cell type, and tissue-resident group 2 innate lymphoid cells (ILC2). The tuft cell/ILC2 axis is driven by the two cytokines interleukin (IL)-25 and IL-13 and is required for tissue homeostasis but turns pro-tumourigenic in the context of chronic inflammation. Our investigation will dissect the underlying mechanisms using a combination of mouse models, immunology and bioinformatics.
Neural Control Of Renin Expression By MicroRNA In Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$805,972.00
Summary
We identified that mice bred to have high blood pressure have an overactive nervous system that affects a gene that controls a hormone in the kidney that increases blood pressure. The proposal will determine the effects of a novel treatment to alter the gene to reverse the changes in the kidney and thereby normalizing blood pressure. This will lead to new therapy and reduce the major risk factor of cardiovascular disease.
A Pharmacological Approach To Define The Contribution Of Nav1.7 To Pain Pathways
Funder
National Health and Medical Research Council
Funding Amount
$501,467.00
Summary
Chronic pain is a debilitating condition that affects the life of one in five Australians and has significant socioeconomic impact. Currently available pain killers often do not work, or have intolerable side effects. We have discovered the most selective blocker for a specific type of sodium channel that is a known pain target and will use this novel molecule to gain insight into the mechanisms of pain and to develop new pain killers.
Characterisation Of Eurl, A Novel Gene Implicated In The Etiology Of Abnormal Brain Development And Intellectual Disability
Funder
National Health and Medical Research Council
Funding Amount
$597,541.00
Summary
Intellectual disability affects around one per cent of Australians, and can arise from genetic abnormalities during fetal life, such as through abnormal regulation of gene expression. We have identified a novel gene, known as eurl, which controls brain assembly as well as the ability of neurons to form functional connections within the brain. We will investigate how this novel gene controls brain development, and characterise eurl as a potential therapeutic target for learning and memory.
Imaging The Activation Of Sensory Nerve Endings That Detect Pain In The Colorectum
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
Within the gastrointestinal tract are sensory nerve endings that detect painful stimuli. In this project a new technique has been developed that allows us to monitor and record the activation of the particular sensory nerve endings that detect painful stimuli. This project will determine how these sensory nerve endings detect pain and how drugs might be used to relieve these unpleasant sensations arising from the gut wall.
Role Of The Paraventricular Hypothalamus In Angiotensin Induced Neurogenic Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$447,014.00
Summary
Hormones released from the kidney are important for setting the level of blood pressure. We have discovered that very low levels of the peptide angiotensin in the blood also leads to activation of specific parts of the brain that drive to increase the nervous system activity to blood vessels and therefore increases blood pressure further. This study will explore the chemical signals in the brain mediating this increase in blood pressure.
Hypothalamic Oxexin-synthesizing Neurons Regulate The Ultradian Basic Rest-Activity Cycle (BRAC); Studies In Transgenic Rats And Mice
Funder
National Health and Medical Research Council
Funding Amount
$588,418.00
Summary
In the hypothalamus region of the brain there is a group of neurons that synthesize a neuropeptide messenger called orexin. In humans, malfunction of orexin neurons results in narcolepsy (abnormal sleepiness) and in disordered metabolism resulting in obesity. Our experiments, conducted in genetically-modified rats and mice, will elucidate the manner in which the orexin neurons integrate our behaviour (eg eating) with our physiological state (eg body and brain temperature, arterial blood pressure ....In the hypothalamus region of the brain there is a group of neurons that synthesize a neuropeptide messenger called orexin. In humans, malfunction of orexin neurons results in narcolepsy (abnormal sleepiness) and in disordered metabolism resulting in obesity. Our experiments, conducted in genetically-modified rats and mice, will elucidate the manner in which the orexin neurons integrate our behaviour (eg eating) with our physiological state (eg body and brain temperature, arterial blood pressure).Read moreRead less
Reduced Baroreceptor Reflex Control Of Heart Rate In Chronic Renal Failure
Funder
National Health and Medical Research Council
Funding Amount
$490,288.00
Summary
People with kidney disease are more likely to die of heart disease than their ailing kidneys. One reason is because their hearts do not respond properly to changes in blood pressure, as the nerve circuits controlling the heart become dysfunctional. We will examine where and why components of this circuit are unable to respond to changes in blood pressure. This will help guide new treatments to reduce the incidence of heart disease and risk of death associated with kidney disease.
Hypothalamic Orexin Neurons And The Medullary Sympathoadrenal Centre: A Key Role In Glucose Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$577,957.00
Summary
Hypoglycaemia or low blood sugar is a major side-effect of the treatment of diabetes. Exposure to hypoglycaemia results in changes in the brain (neuroplasticity) that reduce the awareness of hypoglycaemia, often with serious consequences. Hypoglycaemia triggers the production of several hormones including adrenaline which restore normal blood glucose. This process is incompletely understood. This research project will identify key components of the neurocircuitry that controls blood sugar.