An Analysis Of The Lyn Tyrosine Kinase In The Regulation Of Hematopoiesis And Tumourigenesis.
Funder
National Health and Medical Research Council
Funding Amount
$381,000.00
Summary
The Lyn kinase is an enzyme that is involved in relaying information across the cell membrane. It is a member of a family of genes that have been implicated in tumour development. Lyn is expressed in blood cells and it is involved in a variety of immunological responses. To further our understanding of the role of this enzyme in the context of the whole animal, we have generated two strains of mice, one that is unable to make Lyn protein (Lyn-deficient mice) and one that expresses an activated f ....The Lyn kinase is an enzyme that is involved in relaying information across the cell membrane. It is a member of a family of genes that have been implicated in tumour development. Lyn is expressed in blood cells and it is involved in a variety of immunological responses. To further our understanding of the role of this enzyme in the context of the whole animal, we have generated two strains of mice, one that is unable to make Lyn protein (Lyn-deficient mice) and one that expresses an activated form of the Lyn enzyme (Lyn-up mice). Our previous studies have shown that Lyn-deficient mice have enhanced blood cell formation (hematopoiesis) and develop white blood cell tumours with age, whereas Lyn-up mice show no propensity to develop tumours. In this study we will examine in detail the role that Lyn plays in blood cell formation and tumourigenesis, and we will identify the pathways that underlie the phenotypes in Lyn-deficient mice. On completion of these studies we will have catalogued the molecules and pathways regulated by Lyn, and have an understanding of how Lyn functions in regulating development of specific populations of blood cells, and in suppressing or promoting tumour development.Read moreRead less
The Role Of PAC-1 In Leukocyte Activation And Inflammatory Responses
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
The MAP kinase pathway is fundamental for signalling a variety of cellular responses. This pathway is particularly important for immune responses ie. cytokine signalling, chemotaxis, and proliferation. PAC-1, a MAP kinase phosphatase, is an important regulator of this pathway. Extensive gene profiling of various immune cells using Affymetrix GeneChips identified PAC-1 as a highly regulated molecule in activated mast cells. Mast cells are important inflammatory cells, particularly for rheumatoid ....The MAP kinase pathway is fundamental for signalling a variety of cellular responses. This pathway is particularly important for immune responses ie. cytokine signalling, chemotaxis, and proliferation. PAC-1, a MAP kinase phosphatase, is an important regulator of this pathway. Extensive gene profiling of various immune cells using Affymetrix GeneChips identified PAC-1 as a highly regulated molecule in activated mast cells. Mast cells are important inflammatory cells, particularly for rheumatoid arthritis and asthma. We have shown that PAC-1 deficient mice are highly protected from inflammation and disease in a mouse model of rheumatoid arthritis. This grant aims to extend these exciting initial findings to other inflammatory diseases, particularly asthma and type 1 Diabetes, and to establish the basis for PAC-1 inhibition of disease. This research should establish PAC-1 as a new and important target for inflammatory disease, provide understanding on inflammatory processes, and possibly lead to improved therapies for diseases such as rheumatoid arthritis.Read moreRead less