In a human body, about a million cells are born every second, and a million die by activating a physiological cell death mechanism. If cell death fails to occur, cells accumulate and can develop into cancers. Determining the mechanism and regulation of physiological cell death will provide novel approaches to treat cancers and auto-immune diseases, both of which are characterised by failure of certain cells to die.
Regulation And Mechanisms Of Cell Cycling, Cell Senescence And Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$876,005.00
Summary
Most of our cells are not dividing, but persist in a stable arrested state, yet little is known of the molecular mechanisms that regulate and maintain permanent arrest, or that go wrong when cells start proliferating and turn into cancers. This proposal addresses an area of fundamental, basic biology, that has been largely overlooked. A better understanding of the molecules that regulate cell stability might provide new drug targets so that tumour cell proliferation can be stopped.
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.
The Interferon System In Innate Immune Responses To Disease
Funder
National Health and Medical Research Council
Funding Amount
$836,818.00
Summary
My research investigates special proteins called cytokines in the body’s first-line defence against infection, inflammation and cancer. I will characterise how cells respond, the signals that mediate effects, using sophisticated genetic and new computational techniques to manage and analyse data. One focus is a new cytokine we discovered that protects against infections of the reproductive tract –a global health and socio-economic problem affecting 1 billion people.
Understanding Cell Signalling As A Basis For New Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$863,910.00
Summary
This fellowship will capitalise on my extensive expertise in determining the three-dimensional atomic structures of proteins to uncover fundamental biological mechanisms in cancer and Alzheimer’s disease as a basis for discovering new drugs to combat these devastating diseases.
Pattern Recognition Receptors In Inflammation And Infection
Funder
National Health and Medical Research Council
Funding Amount
$622,655.00
Summary
Innate immunity provides our first line of defence against infections, but pathogens can overcome this system. Understanding how microbes disable innate immunity can teach us how to prevent and/or treat infectious diseases. Innate immunity acts by initiating inflammation. Many important acute and chronic diseases develop when this process is dysregulated. Blocking innate immunity thus has potential to treat many diseases. This project aims to understand innate immunity in these contexts.
I seek the knowledge required to improve prevention, diagnosis and therapy for men with testicular pathologies by studying what controls early sperm development. My research will delineate how cellular signalling molecules lay the foundation for adult fertility, using animal studies, cell culture and clinical samples. Testis samples from testicular cancer patients will be used to test interventions that may kill tumour cells or offer a therapeutic option to men with impaired spermatogenesis.
Skeletal structure is continually modified throughout life to take into account dietary, hormonal and physical changes. This is brought about by three major cell types which either form bone, destroy bone, or sense mechanical and hormonal influences on the skeleton. My work seeks to understand the way these cells are controlled and how they control each other. In this way, I will identify new ways of treating osteoporosis, arthritis, skeletal birth defects and cancer-induced bone disease.
The blood system is made up of different types of blood cells (red cells, white cells, platelets etc). The correct number of each type of cell is controlled by chemical messengers called cytokines. Because overactive cytokine signalling can lead to inflammatory disease and leukemia it is tightly controlled by the other molecules in the body. This project aims to determine the exact mechanism whereby this is achieved with the aim of developing therapies to treat inflammatory disease and leukemia.
Cytokine Signalling And The Regulation Of Normal And Leukaemic Blood Cells
Funder
National Health and Medical Research Council
Funding Amount
$948,684.00
Summary
The formation and actions of white blood cells are regulated by protein messengers called cytokines. Cytokines deliver their message by inducing the activation of signalling pathways that orchestrate the cell’s response to infection but when these responses occur too robustly or at inappropriate times they can lead to autoimmune disease, tissue damage and blood cancers. We study the naturally occurring feedback inhibitors of these processes in order to devise new treatments for these diseases.