The Role Of Dysferlin In Muscular Dystrophy And Skeletal Muscle Membrane Repair.
Funder
National Health and Medical Research Council
Funding Amount
$316,667.00
Summary
Patients who lack the protein dysferlin have muscular dystrophy. These patients are unable to repair their muscle membranes, which get damaged during normal activities. A defect in membrane repair is a new pathway implicated in the muscular dystrophies, and it is likely that other patients will also have defective muscle membrane repair. We will find out how dysferlin mediates its role in membrane repair, and identify other dysferlin-interacting proteins, as these may also underlie disease.
Regulated Targeting Of Cell Death Effectors To And From Mitochondria.
Funder
National Health and Medical Research Council
Funding Amount
$302,764.00
Summary
The protein components of human cells travel to their appropriate intracellular homes by means of the targeting signals they carry. It now seems that a short, but important, list of key regulatory proteins are victims of protein hijacking: these proteins provide critical functions within a particular sub-cellular compartment, but are initially prevented from finding their way to this intracellular home. Only in response to specific physiological signals are these proteins released to find the si ....The protein components of human cells travel to their appropriate intracellular homes by means of the targeting signals they carry. It now seems that a short, but important, list of key regulatory proteins are victims of protein hijacking: these proteins provide critical functions within a particular sub-cellular compartment, but are initially prevented from finding their way to this intracellular home. Only in response to specific physiological signals are these proteins released to find the site at which they act. Human cells carry a molecular death-wish. A specific set of genes encode factors (proteins) that would ensure cellular suicide, or programmed cell death, but this program is only turned on in response to precise environmental signals. Because of the potentially deadly nature of these proteins, several of them are subject to protein hijacking thereby neutralizing their ability to promote cell death. These cell death factors are of great interest, and understanding their location and relocation within cells is crucial, as they represent targets for novel chemotherapies. Selectively triggering a cellular suicide has been proposed as a sensitive means to preventing the uncontrolled cell proliferation at the heart of many cancers. We are studying a set of key regulatory proteins to determine how and when they find their way to the intracellular homes and how this targeting effects their function in programmed cell death.Read moreRead less
Insulin resistance (the inability of ordinarily insulin-sensitive tissues such as muscle and adipose tissue to respond to insulin) contributes to a number of diseases including diabetes and obesity. A key metabolic step in these tissues is the uptake of glucose from the blood stream. This step is accelerated by insulin thus allowing efficient clearance of glucose from the bloodstream after a meal. Our laboratory has played a major role in showing that insulin regulates glucose uptake into muscle ....Insulin resistance (the inability of ordinarily insulin-sensitive tissues such as muscle and adipose tissue to respond to insulin) contributes to a number of diseases including diabetes and obesity. A key metabolic step in these tissues is the uptake of glucose from the blood stream. This step is accelerated by insulin thus allowing efficient clearance of glucose from the bloodstream after a meal. Our laboratory has played a major role in showing that insulin regulates glucose uptake into muscle and adipose tissue by stimulating the movement of a glucose transport protein from inside the cell to the cell surface (see http:--www.imb.uq.edu.au-groups-james-glut4 for an animated description of this process). The purpose of this proposal is to dissect the molecular mechanisms by which this glucose transporter can be held inside the cell in the absence of insulin and then allowed to be released from this site moving to the surface in the presence of insulin. Our studies over the past 5 years have brought us much closer to understanding this process in detail. The identification of the molecules responsible for this regulatory step will not only aid our understanding of this process but it will also provide a valuable target for development of therapeutic agents that can be used to combat insulin resistance.Read moreRead less
Molecular Regulation Of The Serine-Threonine Kinase ULK1 In Autophagy
Funder
National Health and Medical Research Council
Funding Amount
$299,431.00
Summary
Autophagy or self eating is a basic cellular process and can have either beneficial or adverse effects in cancer. It is essential to determine the status of autophagy in patients before considering drugs that block autophagy for therapy. A protein called ULK1 is needed for autophagy and may emerge as a pathological marker for autophagy in cancer as well as a potential drug target. This grant proposal will study ULK1 regulation and will lay the scientific foundation for its medical application.
Infectious pathogens invade cells by hijacking cellular pathways, termed endocytosis, that normally internalise material from outside the cell. We will identify the molecular details of these pathways and how they are modulated in response to infection with Salmonella, a leading cause of human gastroenteritis. Such studies are necessary in order to understand host-pathogen interactions so that treatments can be developed targeting the symptoms of infection