The Role Of The Inositol Polyphosphate 4-phosphatase In Cellular Signalling
Funder
National Health and Medical Research Council
Funding Amount
$454,500.00
Summary
Cells respond to hormones, stress, growth factors and other environmental stimuli resulting in secretion, cell growth, cell division and other specialized functions. These cellular responses are dependent on the generation of intracellular signals that send messages either to the nucleus, the cytoskeleton or membrane compartments and thereby elicit a specific response. A specific subset of signalling molecules that are localized on membrane compartments are called phosphoinositides. We plan to i ....Cells respond to hormones, stress, growth factors and other environmental stimuli resulting in secretion, cell growth, cell division and other specialized functions. These cellular responses are dependent on the generation of intracellular signals that send messages either to the nucleus, the cytoskeleton or membrane compartments and thereby elicit a specific response. A specific subset of signalling molecules that are localized on membrane compartments are called phosphoinositides. We plan to investigate the role of a specific lipid called PtdIns(3,4)P2 that recruits signalling proteins to specific cellular membranes including the inner wall of the plasma membrane and vesicles found within the cell. We have identified and are currently characterizing a novel enzyme called the inositol polyphosphate 4-phosphatase that terminates the signals generated by PtdIns(3,4)P2. We are characterizing mice which lack this enzyme. 4-phosphatase deficient mice demonstrate significant abnormalities in the brain and bone marrow. These mice appear unable to make circulating platelets, small anucleate cells which are vital in preventing bleeding. We will determine how the 4-phosphatase functions in regulating platelet production, by examining the bone marrow and blood of these mice. These studies are significant as platelet production is essential for prevention of blood loss following trauma and also is of vital importance in conditions associated with blood clotting including heart attack and stroke. Secondly we have identified a related enzyme to the 4-phosphatase designated P-Rex-1 which is highly expressed in brain and nerve cells. This proposal aims to determine if P-Rex-1 promotes nerve development.Read moreRead less
The Role Of Melanoma Tumour Antigen P97 (Melanotransferrin) In Melanoma Tumourigenesis.
Funder
National Health and Medical Research Council
Funding Amount
$563,242.00
Summary
The Role of Melanoma Tumour Antigen p97 (Melanotransferrin) in Melanoma Tumourigenesis Melanotransferrin (MTf) is a homologue of the iron transport protein, transferrin, and was one of the first well characterised melanoma tumour antigens. Our published studies have shown that MTf plays an important role in melanoma tumourigenesis in vivo. In this proposal, we will assess if it is associated with melanoma progression in patient samples and examine its role in melanoma growth and metastasis.
Analysis Of T Cell Fate Regulation By Asymmetric Cell Division
Funder
National Health and Medical Research Council
Funding Amount
$287,321.00
Summary
The aim of this research is to study how white blood cell growth is regulated by signals of the immune system. Problems in this process can have drastic effects on the well being of an individual leading to deficiencies in controlling infection and development of diseases such as cancer. Once we understand how these signals regulate white blood cell growth, we can begin to develop therapies to provide protection against these diseases.
Investigating The Role Of Mutant P53 And MCL-1 In The Sustained Growth Of MYC Lymphomas And Strategies For Targeted Therapy
Funder
National Health and Medical Research Council
Funding Amount
$616,940.00
Summary
A large number of human cancers have abnormal expression of a protein called MYC, leading to rapid growth. We found that when another protein called MCL-1 was inactivated, the lymphomas regressed. Importantly, mutations in the tumour suppressor gene called p53 are frequently found in cancer cells and we noticed that this could reduce the dependency on MCL-1. We aim to investigate this further in this grant proposal, in part using a novel drug that targets MCL-1.