How Sweet It Is: Diagnostic Clinical And Experimental Glycoproteomics
Funder
National Health and Medical Research Council
Funding Amount
$473,477.00
Summary
Most human proteins are modified by the addition of complex sugar groups, which are important for the correct function of these key biological molecules. This fellowship will develop a suite of robust mass spectrometry glycoproteomic analytics for use in conjunction with clinical cohorts, model systems and in vitro biochemistry to investigate fundamental aspects controlling N-glycosylation in disease and translation to clinical diagnostics.
The pathology of many acute and chronic diseases associated with the inappropriate activation of genetically encoded programmed cell death pathways, such as sepsis, stroke, diabetes and neurodegeneration, is linked to detrimental inflammation. This project will accurately define at the molecular level how programmed cell death triggers inflammatory responses, and use this knowledge to test novel and next-generation therapeutic strategies in inflammatory-driven diseases.
During injury or infection, our body’s immune system protects us by launching inflammation. But uncontrolled inflammation drives common diseases such as cancer, diabetes, Alzheimer’s and Parkinson's. This research program will reveal how the body deactivates inflammasomes – protein complexes at the heart of inflammation and disease – so we can design better drugs for treating patients with inflammation-driven disease.
Cell death is a normal process that permits the growth and defense of our vital tissues. One kind of cell death, necroptosis, is characterised by the swelling and bursting of cells, triggering inflammation. Necroptosis is a key feature of illnesses ranging from colitis to arthritis, and contributes to the brain and heart damage that follows strokes and heart attacks. Understanding necroptotic cell death will pave the way for new therapies for those who suffer from these devastating conditions.
Identification Of Novel Targeted Therapies For JAK2-driven Leukemogenesis
Funder
National Health and Medical Research Council
Funding Amount
$392,717.00
Summary
Many leukemias are caused by particular signalling molecules becoming too active in blood cells. My research focusses on the molecules that are required by leukemic cells for their growth and survival. I will use mice that are prone to developing leukemia to study how these leukemias can be treated with drugs that block specific molecules. My goal is to discover new ways to treat leukemias that work better and have fewer side effects than current treatments.
Analysis Of Apoptotic Pathways To Develop Better Therapies For Unresponsive Cancers.
Funder
National Health and Medical Research Council
Funding Amount
$130,807.00
Summary
Tight control of the balance between cellular survival and death is important for normal development and to avoid numerous diseases. Inappropriate survival of precancerous cells can contribute to oncogenesis. Anti-cancer therapies act by inducing a cellular self-destruct program in tumour cells, and blocks in pathways controlling this process can lead to resistance to anti-cancer treatments. Defining cell death pathways will enable the development of better therapies for incurable cancers.
Signalosomes And Compartmentalisation In Cellular Homeostasis And Disease
Funder
National Health and Medical Research Council
Funding Amount
$473,646.00
Summary
G protein-coupled receptors are specialised proteins on the surface of cells. They are the targets of 30% of currently available pharmaceuticals. This proposal will examine exciting and novel properties of these proteins that only occur following their assembly into specialised networks in cells. The use of cutting-edge technology will allow us to understand the role of these networks in many diseases. The new information will expand our current knowledge, and facilitate targeted drug design.
Alteration Of Glucose Metabolism By GPCR Activation
Funder
National Health and Medical Research Council
Funding Amount
$444,796.00
Summary
In type 2 diabetes the effect of insulin to stimulate glucose transport in fat cells and skeletal muscle is impaired so there is great interest in identifying insulin-independent mechanisms that increase glucose transport. Several G protein-coupled receptors (GPCRs) regulate glucose transport independently of insulin but the mechanisms involved in these effects are largely unknown. This project investigates how GPCRs regulate glucose homeostasis and will evaluate them as potential treatments.
Using Gene Delivery Tools To Understand And Treat Skeletal Muscle-related Disease
Funder
National Health and Medical Research Council
Funding Amount
$459,270.00
Summary
As a muscle biologist, I study the mechanisms that regulate skeletal muscle size, so that we can develop therapies for muscle wasting. What sets my research apart is my combination of expertise in muscle biology, and the use of recombinant viral vectors for altering the expression of specific genes exclusively in skeletal muscles. Our approaches enable us to study the inner workings of muscles in ways others cannot, and develop promising new therapies for treating muscle diseases.