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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.
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
Reduction Of Chronic Post-surgical Pain With Ketamine - ROCKet Study
Funder
National Health and Medical Research Council
Funding Amount
$4,823,395.00
Summary
Chronic post-surgical pain (CPSP) is a common complication of major surgery, and a significant burden on quality of life and ongoing health costs. Ketamine is a drug used by anaesthetists to treat severe acute surgical pain. Various small studies suggest that it may be unique in its ability to reduce the risk of CPSP. We propose a large trial of ketamine during & after anaesthesia for major surgery to test this. Demonstration of effectiveness would promote widespread change in clinical practice.
Improving Health Outcomes In The Tropical North: A Multidisciplinary Collaboration
Funder
National Health and Medical Research Council
Funding Amount
$5,997,916.00
Summary
Improving Health Outcomes in the Tropical North will strengthen partnerships with research institutions in the NT, Qld, WA, NSW, Vic and SA, by undertaking a research agenda that will help close the gap in Indigenous health disadvantage, protect the north from emerging infectious threats and engage regional neighbours. We will establish a northern Australian network that incorporates Indigenous engagement, mentoring and knowledge translation, and facilitates collaboration with southern partners.
Tackling Chronic Otitis Media And Its Impact On Children: Evidence And Action
Funder
National Health and Medical Research Council
Funding Amount
$286,891.00
Summary
This fellowship aims to improve outcomes for children with otitis media (OM) and hearing loss. This will be achieved through updated national and international guidance on the treatment of OM following a suite of systematic reviews, the trial of new interventions to improve outcomes for children with OM and improving access to treatment for children with OM by establishing an audiology telehealth program for children in rural and remote areas.
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.
Mechanisms Underlying Growth, Lineage Commitment And Differentiation Of Liver Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
Liver disease is a serious health problem. Viral hepatitis, obesity and alcohol can result in end-stage liver disease. Organ transplant is the only treatment available. A widening gap between organ donations and recipients mandates alternative treatments are developed. Cell transplantation and artificial liver devices are alternatives which can use liver progenitor cells. We will investigate how factors grow and convert them into liver cells for treating liver disease patients.
A Genome-wide Search For Genes Underlying The Developmental Origins Of Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,022,552.00
Summary
Epidemic rises in the incidence of many chronic diseases such as obesity, type 2 diabetes, hypertension, coronary artery disease and mental illness have occurred in Australia over the last two decades. Antenatal, early life and childhood factors have been consistently associated with the development of such diseases. We propose to conduct a genome-wide scan in an exceptional longitudinal birth cohort in order to identify the genetic mechanisms linking early life event and adult disease.