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Mechanobiology Of Epithelial Homeostasis In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$876,005.00
Summary
Epithelial tissues, such as the lung, fundamentally protect the body from its external environment. For this, they must detect and respond to danger. My work has discovered a new biological system where cells monitor changes in mechanical forces as a sign of danger. Diseases such as inflammation and cancer occur when this detection system fails. This Fellowship builds on my lab’s pioneering work to understand how force is used to sense danger, and how disease occurs when it goes awry.
Niche Regulation Of Normal And Malignant Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$622,655.00
Summary
Hematopoietic stem cells (HSC) reside in the bone marrow (BM) and make all the cells of the blood system. We study molecules in the BM regulating normal HSC to helping them survive chemotherapy. This means cancer patients should suffer less side-effects from their therapy. Some of these molecule also help leukaemia stem cells (LSC) resist chemotherapy. Inhibitors may a) reduce patient mortality caused by chemotherapy and b) sensitise LSC to chemotherapy enabling long-term cure.
Investigating A Potential New Treatment For Stroke
Funder
National Health and Medical Research Council
Funding Amount
$878,522.00
Summary
Blood clots blocking blood flow to the brain (stroke) are a major cause of death and disability. Safety concerns limit approved therapies to a small subset of patients, highlighting an urgent need for safer, more effective drugs. Our studies show that inhibitors of the enzyme PI3Kbeta increase blood clot permeability, increasing clot ‘dissolvability’, without increased bleeding. This raises the possibility that PI3Kbeta inhibitors may represent a safe and effective adjuvant therapy for stroke.
Multiscale Analysis Of Plasma Membrane Microdomains In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$863,413.00
Summary
The cell surface encloses the cell in a protective barrier but it must also respond to signals coming from outside the cell. To accomplish this, the cell surface is made up of numerous regions each with a specialised role. This proposal aims to examine how lipids and proteins work together to make these specialised regions and aims to understand what goes wrong in diseases such as muscular dystrophy.
Regulation Of Cell Death, Cell Survival And Ubiquitination In Normal Physiology And Disease
Funder
National Health and Medical Research Council
Funding Amount
$851,980.00
Summary
The project will investigate the functions of specific genes and pathways to understand the molecular basis of various diseases. It is based on our data that indicate new roles for (i) cell death in genomic instability in cancer, and (ii) ubiquitination in hypertension, developmental defects, kidney disease, as well as iron homeostasis. The work will lead to new understanding of human disease and discovery of potential new drug targets. It will also provide training of junior scientists.
The human immune system comprises many different types of cells that can detect foreign molecules. My research will lead the way to understanding some of the most abundant, yet least well understood, cells within this system, collectively known as 'unconventional T cells'. This knowledge is essential to optimally and efficiently manipulate the immune system in health and disease.
The research focuses on how gene function is networked and the ways that cells talk to each other to coordinate their activity in the formation of organs and body parts. Knowledge gleaned from these investigations will enhance our understanding of the genetic control underpinning normal development and the errors that lead to birth defects. The elucidation of the process that turns naive cells into the right cell type is essential for the use of stem cells for cell therapy and tissue repair.
Defining The Coordination Of Immune Responses To Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$640,210.00
Summary
Understanding how immune responses are coordinated is critical for the design of new therapies and vaccines to target infectious diseases and cancers. This project will utilise advanced imaging combined with novel tools to dissect the complex interactions that occur between immune cells as they are activated and patrol the body to eliminate infectious pathogens.
I am an cellular immunologist determining the mechanisms by which immunity to foreign organisms is generated, how tolerance to self tissues is maintained, and how the immune system iscriminates between foreign organisms and self.
Mechanisms Of Regulation Of Ribosome Biogenesis And Function In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
The PI3K/AKT signalling pathway drives many cancers and until recently was thought to do so by preventing cancer cell death. We have shown this pathway also regulates the synthesis of ribosomes, the cellular “factories” that make protein and by interfering with PI3K/AKT regulated ribosome synthesis, can kill cancer cells. We aim to establish the mechanisms underlying this regulation of ribosome synthesis and to test the hypothesis that ribosome biogenesis is a novel target for cancer treatment.