Regulation Of Myotubularin Function By The Novel 3-phosphatase Adapter Protein (3-PAP)
Funder
National Health and Medical Research Council
Funding Amount
$488,273.00
Summary
Phospholipids are important components of cell membranes. Phospholipids are turned-on by enzymes called kinases and these phospholipids stimulate a variety of critical functions within the cells. Phospholipids are turned-off by another type of enzymes classed as phosphatases, thereby switching off a broad range of cell functions. Myotubularin is an enzyme, which neutralizes particular type of phospholipids that are involved in the shuttling of proteins between compartments within the cell. Loss ....Phospholipids are important components of cell membranes. Phospholipids are turned-on by enzymes called kinases and these phospholipids stimulate a variety of critical functions within the cells. Phospholipids are turned-off by another type of enzymes classed as phosphatases, thereby switching off a broad range of cell functions. Myotubularin is an enzyme, which neutralizes particular type of phospholipids that are involved in the shuttling of proteins between compartments within the cell. Loss of function of myotubularin, due to inherited genetic changes (mutations), leads to abnormal muscle development manifesting as weakness since birth, and this particular disease is known as 'X-linked myotubular myopathy'. However, there is yet no information on the mechanisms by which failure of protein shuttling (transport) causes myopathy. We have discovered a new protein, 3-phosphatase adapter protein (3-PAP) that links with myotubularin and plays an important role in the function of myotubularin. Our research proposal seeks to clarify the important role of 3-PAP in the development of muscle cells. We propose to study the location of 3-PAP within cells and analyse the influence of 3-PAP on protein shuttling. We have created mice that are deficient in the 3-PAP gene. These special mice will help us understand the importance of 3-PAP in the development and function of nerve and muscle tissue.Read moreRead less
Normally cells only divide when they receive a stimulus from a hormone or growth factor. The PI3-kinase pathway responds to these stimuli and has been implicated in cellular immunity as well as cancer which occurs when cells divide uncontrollably and invade surrounding tissues. We have identified a putative oncogene (cancer causing gene) called MTMR4 that appears to regulate cell growth-invasion and pathogen invasion of immune cells. We aim to characterise the role of MTMR4 in these systems.
The Role Of Seipin In Adipocyte Development And Lipid Droplet Formation
Funder
National Health and Medical Research Council
Funding Amount
$376,258.00
Summary
The prevalence of obesity and its related disorders has reached an alarming level in Australia and other developed countries. Obesity is characterized by the accumulation of fully-differentiated adipocytes loaded with lipid droplets (LDs). We aim to characterize seipin, which regulate both lipid droplet formation and adipocyte differentiation. Results from our proposed studies may offer novel therapeutic strategies against human obesity.
Unravelling A New Fatty Acid Pathway Involved In Neuroexocytosis And Memory
Funder
National Health and Medical Research Council
Funding Amount
$539,631.00
Summary
This proposal build on the establishment by our laboratory of the assay capable of detecting free fatty acids, with great accuracy and sensitivity. Using this assay we have uncovered a completely new pathway highlighting the production of saturated free fatty acids linked to learning and memory. We will fully define how this pathway is regulated in the brain.
The Role Of Phosphatidic Acid In Lipid Storage And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$496,169.00
Summary
The prevalence of obesity and its related disorders has reached an alarming level in Australia and other developed countries. Obesity is characterized by the accumulation of fully-differentiated adipocytes loaded with lipid droplets (LDs). We aim to examine the role of phosphatidic acid in lipid droplet formation and adipocyte differentiation. Results from our proposed studies may offer novel therapeutic strategies against human obesity and type II diabetes.
Elucidating The Mechanism And Function Of Extracellular Vesicle Formation During Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
In humans, billions of cells will die daily as part of normal turnover in various organs. It is vital that dying cells are rapidly removed as their accumulation has been linked to autoimmunity and inflammation. To aid efficient removal of dead cells, dying cells can disassemble into smaller fragments for neighbouring cells to engulf. We aim to understand the machinery that control how dying cells can disassemble into smaller pieces and their function in efficient cell clearance and autoimmunity.