Transcriptional Regulation Of Nociceptor Function And Extreme Genetic Pain Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,007,462.00
Summary
Disorders involving untreatable pain have a devastating impact on a patient’s quality of life. To better treat these conditions, we require a basic understanding of how sensory neurons work. In this study we will define the genetic network involved in regulating pain-sensing neurons. We will then search the genome of pain patients looking for coding mutations within this pain transcriptional network, and we will prove these mutations are causative in fly and mouse systems.
Promoting Regrowth Of Nerve Fibres Into The Epidermis During Diabetic Neuropathy By LRP Agonists
Funder
National Health and Medical Research Council
Funding Amount
$427,102.00
Summary
Nerve damage can develop post injury or disease and is often very debilitating, slow to heal and can cause increased pain. Our work aims to examine a new class of molecules that we show can activate selected fat-receptors on nerve cells to guide the growth of regenerating nerves. We will determine how these receptors function with the aim of developing a novel class of therapeutics directed at healing nerve damage.
Enhanced Sensory Perception Via Jitter Reduction And Neural Synchronisation Evoked By Subsensory Electrical Noise Stimulation – Restoring Sensitivity In Peripheral Neuropathy
Funder
National Health and Medical Research Council
Funding Amount
$318,473.00
Summary
The elderly and patients with diabetes are at high risk of losing sensation in their feet and currently no treatment for this condition exists. This loss of feeling leads to falls, fractures and foot ulcers, which in many cases end with amputation. We have developed a new subsensory stimulation technique which for the first time restores lost sensation. Development of this novel treatment is made possible by a multi-disciplinary team of engineers, neuroscientists, physiologists and podiatrists.
SENSORIMOTOR AND AUTONOMIC DYSREGULATION IN HEREDITARY SENSORY AND AUTONOMIC NEUROPATHIES
Funder
National Health and Medical Research Council
Funding Amount
$50,406.00
Summary
Specific genetic mutations can lead to widespread changes in the body. Here we are looking at the congenital Hereditary and Sensory Autonomic Neuropathies, the most common of which primarily affects Eastern European Jews. Affected individuals have difficulty walking and controlling their blood pressure, and also have an indifference to pain. This series of experiments aims to increase our understanding of the underlying neurophysiological disturbances.
Investigating The Interaction Of Precursor Inner Membrane Proteins With Translocase Components
Funder
National Health and Medical Research Council
Funding Amount
$585,274.00
Summary
Proteins are synthesised on ribosomes located in the cellular plasm, and then moved to their site of action by specialised transport systems. Import of proteins to the mitochondria involves translocase pores, which come equipped with receptors and chaperones. We are investigating the targeting and transfer of newly synthesised proteins of the MCF carrier family from the ribosomal machinery to the inner mitochondrial membrane, focusing on interaction with chaperones in the intermembrane space.
Nerve Excitability Assessment: A Novel Biomarker For The Early Detection Of Diabetic Neuropathy.
Funder
National Health and Medical Research Council
Funding Amount
$375,203.00
Summary
Australia has one of the highest rates of diabetes in the world. Diabetes may be complicated by the development of nerve damage, causing weakness and pain in the upper and lower limbs. The cause remains unclear and there are no tools available for its early detection. This study will provide further information about the cause of diabetic neuropathy and will investigate more sophisticated means for its early detection.
Expanding Diagnostic Approaches For Lynch Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$1,269,355.00
Summary
Currently, there are ~1,000 families who have attended Family Cancer Clinics across Australia who have the hallmarks of having Lynch syndrome, a hereditary bowel cancer syndrome, but who have no gene defect identified, i.e. their cancer is unexplained. Clinicians are challenged by these “Lynch-like” patients as their family cancer risk is unknown. Our research has identified new gene defects in Lynch-like patients. Our aim is to optimise clinical testing approaches for Lynch-like patients.
HEREDITARY ENDOCRINE CANCER: A MODEL BASED ON PHAEOCHROMOCYTOMA- PARAGANGLIOMA SYNDROMES
Funder
National Health and Medical Research Council
Funding Amount
$875,894.00
Summary
Phaeochromocytomas and paragangliomas are tumours remarkable for their very high heritability. They have a high burden of disease themselves, and their associated hereditary syndromes include risks for other malignancies. Our study will rationalize the pathological approach to diagnosing these hereditary syndromes, find new therapeutic targets for metastatic disease, and provide a template for other cancers with high heritable component.
Intrinsic Hearing Protection Mechanisms: A Pathway To Prevention Of Noise-induced Hearing Loss
Funder
National Health and Medical Research Council
Funding Amount
$625,900.00
Summary
Noise-induced hearing loss (NIHL) is a significant contributor to the total burden of disease. We recently determined that when the ear is exposed to sustained noise, the cochlea is protected from damage by activation of a specific (P2X2) receptor, evident as reversible hearing adaptation. This study will determine the downstream signalling from this receptor. This will support assessment of vulnerability to NIHL and contribute to development of hearing therapeutics.
Nodal Function In Peripheral Neuroinflammatory Disorders: Target Antigens, Functional Significance And Treatment Response
Funder
National Health and Medical Research Council
Funding Amount
$605,172.00
Summary
Inflammatory neuropathies are autoimmune disorders which produce severe disability and represent a costly burden to the healthcare system, but the causes remain unknown. Recent evidence from our team suggests that antibodies against parts of the peripheral nerve at the node of Ranvier are involved. The project aims to identify these specific targets and monitor treatment responsiveness, stabilise nerve function and prevent persistent disability.