Cardiovascular Effects Of Enhanced Leptin Signalling
Funder
National Health and Medical Research Council
Funding Amount
$1,200,972.00
Summary
Leptin treatment causes weight loss, but leptin also increases blood pressure. We wish to determine if increasing leptin signalling, by modifying signal transduction pathways within leptin sensitive cells in the brain, can reduce weight without increasing blood pressure.
Regulation Of Ca2+/calmodulin Dependent Protein Kinase Kinase-2 By Phosphorylation
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
This project will study the regulation of an enzyme called CaMKK2, which plays a pivotal role in controlling a number of important biological functions including brain development, regulation of appetite, energy metabolism and blood pressure. Understanding how this enzyme is regulated may open new avenues for treating Type 2 diabetes, obesity, and cardiovascular disease.
The research will investigate the mechanisms by which our brains are able to listen selectively to sounds of interest in competing background noise. This will be investigated in normal hearing subjects, those with partial deafness and in profoundly deaf patients who use a cochlear implant. If deaf patients can learn to use cues to enhance detection of sounds of interest this could have an impact on the effectiveness of hearing aids and cochlear implants in noisy listening situations
Insulin triggers glucose uptake into fat and muscle tissue, a process that is defective in type 2 diabetes. Insulin does this by triggering a complex cascade of actions once it binds to muscle and fat cells. We will analyse the function of a crucial protein within this cascade. This protein is mutated in humans with severe insulin resistance and our proposed project will dissect how this protein works potentially providing a novel drug target to treat diabetes.
Cells are building blocks of living things and require signalling pathways to communicate their functions. We discovered a new signalling pathway in flies that remarkably exists in yeast and plants to more complex organisms like mice and man. We will study this new signalling pathway in flies to find out how and why it communicates in cells. As flies and humans share similar genes, our studies will inform how this previously unknown signalling pathway functions from simple to complex organisms
The Targeting Of Flt3, C-Kit And Src As Therapies For C-Cbl-associated Myeloid Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$535,416.00
Summary
Most leukaemias are incurable so it is important to find new treatments. For this to occur it is essential that the mutated genes causing leukaemia are identified. We have generated a mouse with a mutation in a gene, c-Cbl, that promotes the activation of a number of proteins involved in leukaemia development. By treating c-Cbl mutant mice with drugs that target these proteins we intend to identify the most effective treatments for human leukaemias associated with c-Cbl mutations.
Studies Of Cullin 5 Deficiency For Novel Insights Into SOCS Redundancy And Specificity
Funder
National Health and Medical Research Council
Funding Amount
$658,571.00
Summary
Cytokines are hormones that regulate blood cell production and function. The research proposed in this application focuses on the biological roles and biochemical mechanisms of action of an important family of proteins that control the actions of cytokines, thereby allowing their beneficial effects in coordinating oxygen transport, blood clotting and responses to infection, while preventing the harmful effects of excess responses, such as myeloproliferative diseases or autoimmunity.
Mechanisms Of Regulating Gene Expression Via Selective MRNA Transport
Funder
National Health and Medical Research Council
Funding Amount
$424,076.00
Summary
A critical step in the gene expression pathway that is altered in cancer is nuclear export of mRNA. We have demonstrated that mRNA export is not constitutive, but highly selective and can regulate distinct biological processes through poorly understood mechanisms. This project aims to dissect the molecular mechanisms of regulating gene expression via selective mRNA transport. This will establish selective mRNA export as a novel area of research in cancer biology.
Triple negative breast cancer (TNBC) is an aggressive disease subtype that lacks targeted therapies. We have identified a protein associated with TNBC termed SgK269 that regulates the transmission of signals instructing the cell to grow and migrate. SgK269 associates with a closely-related protein termed SgK223 to form a signalling complex. The aim of this project is to characterise the role of this signalling complex in TNBC and determine whether it represents a potential therapeutic target.
Single-cell Optical Window Imaging In CDK1-FRET Biosensor Mice To Assess Tissue Stiffness And Optimise Delivery And Therapeutic Response To Gemcitabine/Abraxane In Pancreatic Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$676,979.00
Summary
Inefficient drug response in solid tumour tissue is commonly a limiting factor in the clinical effectiveness of cancer therapies. Using cutting-edge imaging technology and 3D models that mimic the disease, we have mapped areas of poor drug response within distinct regions of tumours. Here, we pinpoint and specifically target key factors limiting efficient drug targeting in order to improve the encouraging anti-cancer profile of the new drug combination Gemcitabine/Abraxane in pancreatic cancer.