A Novel Role For Proteolysis In Promoting Inner Ear Cell Injury And Hearing Loss
Funder
National Health and Medical Research Council
Funding Amount
$972,818.00
Summary
Nearly 40% of hearing loss is attributable to traumatic noise exposure. This project will test a new idea that cells in the inner ear are damaged and die via noise-induced proteolysis, and investigate whether a similar mechanism operates during age-related hearing loss. It will open new avenues for therapies to preserve hearing where trauma is unavoidable, or has occurred through accident or incident.
Investigating The Role Of SERPINB6 In Cochlear Function And Deafness
Funder
National Health and Medical Research Council
Funding Amount
$570,803.00
Summary
In 2010 a novel genetic mutation was identified that causes progressive hearing loss in humans, however, it was not established why this mutation leads to the disease. We propose that the mutation renders cells of the inner ear more susceptible to death caused by noise trauma. We will investigate this in a mouse model of the human condition. This could lead to the development of therapies that prevent hearing loss.
Mechanisms Responsible For Pancreatic Beta Cell Death And Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Diabetes is the fastest growing chronic disease both in Australia and worldwide. Current treatments are lacking effectiveness. Therefore, there is an urgent need to revolutionise diabetes therapy. Diabetes is caused by the failure of cells within the pancreas to produce sufficient insulin, resulting in uncontrolled blood sugar levels. This research proposal aims to investigate the processes and factors leading to this phenomenon in order to develop new strategies to overcome them.
Cancer is constantly being suppressed in our bodies by a process that stops damaged cells from growing: 'senescence'. The mechanism that translates the damage stimuli into this state of permanent cell arrest is only partially known. We have identified a protein that appears to drive this restraint. The possibility of manipulating this process to prevent and cure cancer makes it in important target to study.
Targeting Chromosomal Instability By Metabolic Stress
Funder
National Health and Medical Research Council
Funding Amount
$612,652.00
Summary
The most intractable cancers gain and lose DNA as they grow, making them highly variable and drug resistant. We have found that mild disruptions to their use of energy can specifically kill cells with this kind of genetic instability. In this project we will characterize the mechanism by which metabolic stress affects cell division and the survival of genetically unstable cells. Our objective is to find treatments with no effects on normal cells that eliminate unstably dividing cancer cells.
Regulation Of Mitochondrial Fission, Fusion And Distribution
Funder
National Health and Medical Research Council
Funding Amount
$480,128.00
Summary
Mitochondria are subcellular compartments that produce most of the energy for our bodies, in the form of ATP. They were once thought of as small bean-shaped organelles floating around in our cells, but it is now known that mitochondria instead form networks of tubules that undergo changes in their shape through both fission and fusion events. Mitochondria are transported along microtubules that act as highways in the cell so that they can be distributed to areas that require ATP or other special ....Mitochondria are subcellular compartments that produce most of the energy for our bodies, in the form of ATP. They were once thought of as small bean-shaped organelles floating around in our cells, but it is now known that mitochondria instead form networks of tubules that undergo changes in their shape through both fission and fusion events. Mitochondria are transported along microtubules that act as highways in the cell so that they can be distributed to areas that require ATP or other specialist functions such as uptake and release of calcium. In specialist cells, mitochondria are organised even further. Sperm cells contain mitochondria packed around the mid-piece of the flagellum so that ATP can be utilised directly for swimming. Proper mitochondrial distribution also appears to be required for nerve cell development and function while in pancreatic cells they sit at the cell's edge and help regulate the secretion of insulin into the bloodstream. While we now realise the great importance of mitochondria to the cell, we are only beginning to work out how these organelles undergo the drastic morphological changes which are essential for cellular function. Of the few known components involved in shaping mitochondria, some have been found to be essential to life and their gene mutations are linked to neurological disorders, while others appear to be recruited in the activation of cell death pathways. In this application, we plan to identify and characterise the proteins involved in movement and shaping of these organelles. Understanding the fundamental mechanisms of mitochondrial dynamics will provide valuable insights into mitochondrial segregation and specialisation in cells and their defects that lead to disease.Read moreRead less
The role of a novel protein, interferon epsilon, in reproductive tract immunity. This project aims to develop a world-first description of a new protein that has a protective role against female reproductive tract infections. This unique protein, called interferon epsilon, was discovered in our laboratory. This project will facilitate development of new therapeutic approaches of benefit in diseases such as Chlamydia and Herpes Simplex Virus.