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Developing Novel Molecules To Down-Regulate Src Family Tyrosine Kinases
Funder
National Health and Medical Research Council
Funding Amount
$201,261.00
Summary
Leukaemia and cancer cells have altered biochemical properties resulting in their high rate of growth compared to normal cells. One of the common biochemical characteristics of cancer-leukaemia cells is augmented activity levels of enzymes called tyrosine kinases. A major group of tyrosine kinase involved in several cancer-leukaemia types is called the Src family of tyrosine kinases. One member of this family called Lyn has been our focus of study for several years, investigating the signalling ....Leukaemia and cancer cells have altered biochemical properties resulting in their high rate of growth compared to normal cells. One of the common biochemical characteristics of cancer-leukaemia cells is augmented activity levels of enzymes called tyrosine kinases. A major group of tyrosine kinase involved in several cancer-leukaemia types is called the Src family of tyrosine kinases. One member of this family called Lyn has been our focus of study for several years, investigating the signalling pathways that it is involved in. This molecule has also been implicated in several specific leukaemia (Chronic Myeloid Leukaemia and Acute Myeloid Leukaemia) as well as cancer (Prostate, Colon, Breast) in recent years. We have identified a novel mechanism of down-regulation of this enzyme mediated by an adapter molecule called Cbp, which recruits the Lyn inactivating molecules Csk-Ctk as well as SOCS-1; together they inhibit the activity of Lyn and degrade the enzyme. Using our knowledge of the essential interaction elements of Cbp we will design and test various mini-Cbp molecules for their ability to inactivate and degrade Lyn in leukemic and cancer cells. These molecules may allow us to develop novel therapeutics capable of inactivating-degrading specific tyrosine kinases in cancer and leukaemia.Read moreRead less
Improving Stroke Outcomes: Attenuating Progression And Recurrence
Funder
National Health and Medical Research Council
Funding Amount
$9,331,996.00
Summary
Stroke is the second most common cause of death and major cause disability. There are few proven interventions, so we need to introduce new ones. We developed a bench to bedside program to introduce new stroke therapies and its early secondary prevention. Our general goal is to provide evidence for their effectiveness and safety. We will use animal stroke models, markers in the blood to help diagnose and predict stroke outcome and imaging to help select patients for several clinical trials.
Evaluating the feasibility and effect of using a hospital wide coordinated approach to introduce evidence-based changes for pain management. This project will develop a comprehensive educational program and approach to pain management for public and private hospitals that could be used by other hospitals elsewhere. An educational program for hospitals staff, and specifically for Pain Resource Nurses, will be produced. This project has the potential to minimise the experience of pain and prevent ....Evaluating the feasibility and effect of using a hospital wide coordinated approach to introduce evidence-based changes for pain management. This project will develop a comprehensive educational program and approach to pain management for public and private hospitals that could be used by other hospitals elsewhere. An educational program for hospitals staff, and specifically for Pain Resource Nurses, will be produced. This project has the potential to minimise the experience of pain and prevent widespread complications associated with pain for all hospitalised patients, irrespective of diagnosis or reason for admission. It is also envisaged that this project will establish a model of change that could be used to facilitate evidence-based practice in other aspects of healthcare apart from pain.Read moreRead less
A prospective evaluation of the impact of the nurse practitioner role on emergency department service and outcomes. The local hospital emergency department (ED) is a prominent and highly utilised service in Australian communities but demand on EDs is increasing, resulting in significant service delays. This project will study the composition of ED clinical teams around Australia and their impact on improving the timeliness and quality of emergency clinical care.
Mature red cells develop from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (Epo). Previously we had identified that the protein Lyn must be present inside primitive red blood cells for Epo to stimulate them to become mature functional cells. We will determine the role of several molecules that interact with Lyn including Cbp, Liar and LACM, towards apects of red blood cell development.
Leukaemia-cancer cells have altered biochemical properties resulting in their high rate of growth compared to normal cells. One of these is augmented activity of enzymes called tyrosine kinases including members of the Src family. One called Lyn has been implicated in several leukaemias as well as cancer. We have identified a novel mechanism of down-regulating this family of enzymes mediated by small proteins. These may allow us to develop novel therapeutics for cancer-leukaemia treatment.