Investigating The Role Of TGF-beta In Resident Memory T Cell Induction And Maintenance
Funder
National Health and Medical Research Council
Funding Amount
$92,495.00
Summary
I am a research scientist interested in the immune system. Specifically, I intend to investigate immunological memory, which is the basis of vaccination. This refers to the ability of certain immune cells such as T and B cells to ‘remember’ a pathogen, so that a rapid and enhanced response can be generated upon re-infection with the same pathogen. This can be investigated by experimental techniques such as flow cytometry, histology and confocal microscopy on cells from infected mouse tissue.
The Role Of Mal In Toll-like Receptor Signal Transduction Of The Pro-inflammatory Response.
Funder
National Health and Medical Research Council
Funding Amount
$472,500.00
Summary
Sepsis kills more people per year than the cancers of the breast, colon, prostate and pancreas combined. Sepsis occurs in 1 of 50 hospital admissions and is the leading cause of death n intensive care units. The instance of sepsis has doubled in the last decade and is expected to increase. One of the major causes of sepsis si lipopolysaccharide (LPS), the main constituent of gram-negative bacteria's cell wall, and the prototypic inducer of the pro-inflammatory response of the innate immune syste ....Sepsis kills more people per year than the cancers of the breast, colon, prostate and pancreas combined. Sepsis occurs in 1 of 50 hospital admissions and is the leading cause of death n intensive care units. The instance of sepsis has doubled in the last decade and is expected to increase. One of the major causes of sepsis si lipopolysaccharide (LPS), the main constituent of gram-negative bacteria's cell wall, and the prototypic inducer of the pro-inflammatory response of the innate immune system. Dysregulation of the pro-inflammatory response can lead to sepsis. Recently, the mammalian receptor for LPS was found to be Toll-like receptor (TLR)-4, the activation of which activates a signal transduction pathway that initiates the pro-inflammatory response. We have previously shown a key role for an adapter protein called Mal in mediating signal transduction pathways upon activation of TLR-4. Interaction of Mal with a key signal transduction mediator called TRAF6 has been shown to induce the activation of the pro-inflammatory response. Furthermore, Mal has been found to undergo degradation which may indicate a means of regulating the continued activation of the pro-inflammatory pathway. This research program will investigate the role of Mal in mediating signal transduction in TLR activated macrophages, key responsive cells of the innate immune system to microbial infection. A greater understanding of these processes will assist in the development of therapeutics to alleviate the consequences of microbial-induced inflammation, including chronic inflammatory diseases and sepsis.Read moreRead less
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.
Using A Novel Assay That Detects Antigen Specific CD4+ And Regulatory T Cells To Further Understand Reconstitution Of Antigen Specific Immune Response Post Anti-retroviral Therapy In Subjects With HIV And In The Diagnosis Of Latent TB
Funder
National Health and Medical Research Council
Funding Amount
$102,780.00
Summary
The process by which the immune system recovers after commencement of therapy for HIV is not well understood. We will use a new test to monitor the immune system's ability to recognise and react to different antigens inorder to understand the factors that affect immune recovery in patients on therapy for HIV. We will also evaluate the use of this new test in the diagnosis of latent TB. Improvement in detection will lead to treatment of latent TB thus reduction of cases of active TB.
Structure And Composition Of The Pre-T Cell Receptor-CD3 Complex
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
In order to recognize a wide variety of pathogens, humans produce many different T cell receptors (TCRs) by the process of gene-rearrangement. However, gene-rearrangement may not always lead to a functioning TCR. We are studying the pre-TCR protein that is responsible for monitoring the success of gene-rearrangement and is thus essential for the formation of a robust immune system. Understanding pre-TCR function will lead to new treatments for immune related diseases.
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.
I am an immunologist focusing on understanding how can we combat chronic infections while preventing autoimmunity. This proposal aims to investigate how a poorly understood subset of lymphocytes called Tfh cells are regulated to promote the formation of protective antibodies, and prevent development of harmful antibodies that go on to cause or exacerbate diseases such as lupus, rheumatoid arthritis and type 1 diabetes. Our discoveries will illuminate novel drug targets for these diseases and hel ....I am an immunologist focusing on understanding how can we combat chronic infections while preventing autoimmunity. This proposal aims to investigate how a poorly understood subset of lymphocytes called Tfh cells are regulated to promote the formation of protective antibodies, and prevent development of harmful antibodies that go on to cause or exacerbate diseases such as lupus, rheumatoid arthritis and type 1 diabetes. Our discoveries will illuminate novel drug targets for these diseases and help generate more potent vaccines.Read moreRead less
Multiple Paths Of TFH Differentiation And Their Impact On B Cell Protection Against Infection
Funder
National Health and Medical Research Council
Funding Amount
$923,466.00
Summary
Collaboration between T and B cells is crucial for immune protection and underpins current vaccine strategies. We have revealed an unappreciated flexibility that exists in T cell responses which varies the instructions they give B cells. It is likely this tailors immune responses to ensure protection to countless infectious diseases. This project uses cutting-edge technologies to understand this flexibility and has important implications for vaccine design and treatment of infectious disease.