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.
Transcriptional Regulation Of Hematopoietic Commitment
Funder
National Health and Medical Research Council
Funding Amount
$289,985.00
Summary
Blood cell formation is a tightly regulated process and provides an important model for our understanding of blood homeostasis. Perturbations result in a number of disorders such as leukaemia. The application of stem cells to many diseases is being pursued; yet, to be successful knowledge of normal cellular behavior is crucial. I aim to improve our understanding of these processes and help to provide the framework for future studies aimed at more directly manipulating blood cell functions.
The Role Of Cell Cycle Control In Haemopoietic Stem Cell Fate Decisions.
Funder
National Health and Medical Research Council
Funding Amount
$390,974.00
Summary
My research has focused on understanding how the process of cell division can result in different outcomes for adult blood stem cells. I am interested in determining the role of bone and blood vessels in the regulation of blood stem cells and in the development of blood diseases (myeloprolifertive disease). I will also determine the effects of changing the cell cycle with drugs to improve transplantation of blood stem cells.
The emerging interdisciplinary field, mechanobiology, is focused on understanding how cells sense their surroundings and transfer biomechanical signals to initiate cellular changes. I aim to develop hydrogel platforms with differential stiffness patterns to study cellular mechanotransduction and to generate heart muscle cells. The findings have the potential to greatly improve the clinical outcomes where more than 10 clinical trials failed to show successful regeneration after heart attack.