Professor Godfrey is an immunologist with a long standing history as a pioneer in the study of a specialised type of white blood cell, known as NKT cells. NKT cells are activated in response to lipid-based molecules that are thought to alert the immune system, via NKT cell activation, to the presence of infectious agents or other abnormalities. A better understanding of how NKT cells function will provide new approaches to battling a broad range of diseases where these cells are implicated, incl ....Professor Godfrey is an immunologist with a long standing history as a pioneer in the study of a specialised type of white blood cell, known as NKT cells. NKT cells are activated in response to lipid-based molecules that are thought to alert the immune system, via NKT cell activation, to the presence of infectious agents or other abnormalities. A better understanding of how NKT cells function will provide new approaches to battling a broad range of diseases where these cells are implicated, including cancer, autoimmunity, allergy and infection.Read moreRead less
I am an immunologist, working to understand the function of NKT cells, and how these cells can be manipulated as a means of immune therapy for a range of immunologically related diseases.
The Role Of C-Cbl In The Regulation Of T Cell Signalling And Development
Funder
National Health and Medical Research Council
Funding Amount
$527,250.00
Summary
c-Cbl is a member of a multi-adaptor protein family that can interact with many signalling proteins via its different domains. Cbl proteins have been implicated as negative regulators of signalling pathways involving protein tyrosine kinases (PTKs). PTKs are enzymes which add phosphate groups to tyrosine residues on other protein substrates, and the process of tyrosine phosphorylation acts as a potent biochemical switch to turn signalling cascades on and off. Studies of Cbl-deficient (knockout) ....c-Cbl is a member of a multi-adaptor protein family that can interact with many signalling proteins via its different domains. Cbl proteins have been implicated as negative regulators of signalling pathways involving protein tyrosine kinases (PTKs). PTKs are enzymes which add phosphate groups to tyrosine residues on other protein substrates, and the process of tyrosine phosphorylation acts as a potent biochemical switch to turn signalling cascades on and off. Studies of Cbl-deficient (knockout) mice show that Cbl proteins are important in regulating the development of, and signalling by, cells of the immune system called T cells. c-Cbl knockout mice show greatly enhanced PTK-signalling responses and deregulated activity of a PTK called ZAP-70. The mechanism of this is not known, but analysis of a c-Cbl mutant mouse shows that this is not dependent on the tyrosine kinase binding (TKB) domain of c-Cbl. Therefore other functional domains of Cbl must be responsible for the increased signalling response in the c-Cbl knockout mouse. One candidate is the highly conserved RING finger domain which can modify Cbl-associated PTKs by addition of ubiquitin molecules. Ubiquitination of a protein often, but not always, leads to its degradation, and this could be how Cbl controls the strength and duration of signalling in T cells. However there may be other functions of the conserved RING finger yet to be identified. c-Cbl itself is prominently and very rapidly modified by tyrosine phosphorylation on tyrosine 737 by the Fyn PTK following T cell activation, but the role of this modification is not known and could also be essential for c-Cbl s function in T cells. We plan to investigate the roles of the RING finger domain and Fyn-mediated tyrosine phosphorylation in c-Cbl regulation of T cell signalling by analyzing knock-in mice that carry specific mutations disrupting the RING finger or tyrosine 737 in the c-Cbl gene.Read moreRead less
Understanding The Role Of Innate Immune Cells In Regulating Gut-associated Lymphoid Tissues At Steady-state And In Disease
Funder
National Health and Medical Research Council
Funding Amount
$365,126.00
Summary
The intestine is the largest surface area forming a protective barrier between the external environment and the body. It represents the first line of defence against invading pathogens. The immune system of the intestine is critical to protect this tissue -any breakdown leads to profound and progressive inflammatory disease of the gut such as chronic inflammatory bowel disease. Our work will determine the critical the mechanisms that protect the gut opening the door to targeted intestinal immuno ....The intestine is the largest surface area forming a protective barrier between the external environment and the body. It represents the first line of defence against invading pathogens. The immune system of the intestine is critical to protect this tissue -any breakdown leads to profound and progressive inflammatory disease of the gut such as chronic inflammatory bowel disease. Our work will determine the critical the mechanisms that protect the gut opening the door to targeted intestinal immunotherapeutics.Read moreRead less
The Mechanisms Of Epithelial Cell Survival That Govern Thymus Function
Funder
National Health and Medical Research Council
Funding Amount
$620,967.00
Summary
The thymus is an organ dedicated to the production of crucial immune cells, called T lymphocytes. Cancer treatments, such as radiation or chemotherapy, destroy thymic function and impair immune recovery in patients. We aim to uncover molecular processes that govern the life and death decisions of cells in the thymus. Our goal is to then use this information to develop treatments to protect this critical organ from damage and improve immune recovery following radiation or chemotherapy.
Characterization Of H. Pylori –specific CD4 T Cell Responses And The Evaluation Of The Basic Requirements For The Development Of An Effective Anti-H. Pylori Vaccine
Funder
National Health and Medical Research Council
Funding Amount
$313,161.00
Summary
H. pylori infect over half of the global population. Although infection results in asymptomatic gastritis in most cases 10 % develop gastric ulcers and cancer. Current vaccination strategies have failed to protect humans from infection. We aim to characterise the main immune cells involved in H. pylori infection, specifically the bacteria-specific CD4 T cells. We will then try to understand the basic requirements for a successful vaccine in order to develop new, improved anti-H. pylori vaccines.
Defining the immunological roles of stromal cells within lymphoid tissues. The populations of endothelial and mesenchymal cells that construct the lymphoid tissues are being revealed as key players in the priming and orchestration of immune responses. Yet, fundamental knowledge of the molecular makeup and the functions of these stromal cells, particularly their roles in immune responses, is sorely lacking. This project will utilise a multidisciplinary approach including advanced imaging and bioi ....Defining the immunological roles of stromal cells within lymphoid tissues. The populations of endothelial and mesenchymal cells that construct the lymphoid tissues are being revealed as key players in the priming and orchestration of immune responses. Yet, fundamental knowledge of the molecular makeup and the functions of these stromal cells, particularly their roles in immune responses, is sorely lacking. This project will utilise a multidisciplinary approach including advanced imaging and bioinformatics to dissect the functions of the lymphoid stromal cells and their roles in the swelling of lymphoid tissues during immune responses. This will provide vital information about the biology of these understudied cells and reveal the ways in which they support the generation of immunity.Read moreRead less
My research is aiming to study how the immune system controls viral infections in transplant patients and use this information to bolster their immunity in a test tube, providing protection against a virus the patient is unable to fight after their transplant. We are also trying to develop new strategies to use patient's own blood cells which will be grown in the laboratory and returned to the patient, resulting in a full recovery.
Understanding the immune response is proving extremely complex and promising results for disease treatments from animal models are often difficult to translate to new clinical therapies. My research is unearthing weaknesses in our current knowledge of the immune system and seeking to replace them with a foundation that can exploit new developments in computer modelling and systems biology. In this way I aim to rationally manipulate the immune response.
Development And Function Of NKT Cell Subsets In Humans
Funder
National Health and Medical Research Council
Funding Amount
$533,828.00
Summary
NKT cells are a type of white blood cell that help to control the function of the immune system. Many studies have reported an association between low NKT cell levels and increased rates of cancer and autoimmune diseases such as type 1 diabetes (T1D). Unfortunately, NKT cells are a relatively recent discovery and their function is not well understood, especially in humans. For example, it has only recently been discovered that there are different types of NKT cells with different functions. This ....NKT cells are a type of white blood cell that help to control the function of the immune system. Many studies have reported an association between low NKT cell levels and increased rates of cancer and autoimmune diseases such as type 1 diabetes (T1D). Unfortunately, NKT cells are a relatively recent discovery and their function is not well understood, especially in humans. For example, it has only recently been discovered that there are different types of NKT cells with different functions. This lack of knowledge has prevented us from understanding how NKT cells normally prevent disease, and how we should treat diseases associated with low NKT cell numbers. In this project, we will study human NKT cells to determine how many different subsets exist, how they develop, and what role they play in the immune system. Importantly, we will use our knowledge to compare NKT cells from healthy donors and patient groups with T1D and cancer to determine exactly what is wrong with the NKT cells in these people. While both diseases are already linked to low NKT cell numbers, we do not know how these problems arise, or if some types of NKT cells are more important than others. Our study will determine how different types of NKT cells develop and function in humans and therefore allow a much more detailed understandng of how to diagnose and treat NKT cell deficiencies associated with different diseases.Read moreRead less