Characterisation And Targeting T Cellular Metabolism To Improve Control Of Chronic Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$791,427.00
Summary
CD8+ T cells are the frontline warriors of our immune system that can eliminate infected or cancerous cells. However, diseases caused by overwhelming viral infections are associated with widespread impairments in immunity and cellular metabolism. Here, we propose to examine molecular pathways involved in cellular metabolism that could be utilized to improve therapies against viral infection and cancer.
Protecting Against Malaria Through Liver-resident Memory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,196,853.00
Summary
We have shown that formation of liver-resident memory T cells (Trm), a newly discovered type of immune cells, can be induced by an innovative vaccination strategy called prime and trap for highly efficient protection against malaria in mice. Here, we will enhance prime and trap vaccination efficacy by defining the conditions that maximize liver Trm-mediated protection and will characterize simian and human liver Trm cells, paving the way to create the most efficient human malaria vaccine to date
The Role Of Kdm1a In Epigenetic Regulation Of Virus-specific T Cell Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$510,982.00
Summary
Recovery from infection, or vaccination, results in the establishment of protective immunity that persists for the life of an individual. Unfortunately, our understanding of how protective immunity is established and maintained after infection or vaccination is lacking. This proposal will determine whether specific enzymes involved in rewriting the genetic blueprint are key for establishing and maintaining this protective capacity. Understanding these mechanisms has implications for vaccination ....Recovery from infection, or vaccination, results in the establishment of protective immunity that persists for the life of an individual. Unfortunately, our understanding of how protective immunity is established and maintained after infection or vaccination is lacking. This proposal will determine whether specific enzymes involved in rewriting the genetic blueprint are key for establishing and maintaining this protective capacity. Understanding these mechanisms has implications for vaccination and improved immunotherapy strategies for cancer.Read moreRead less
The Mechanisms Of Establishing, Maintaining Immunological Memory And Immunodominance Hierarchy
Funder
National Health and Medical Research Council
Funding Amount
$234,750.00
Summary
The hallmark of the adaptive immune response is the development of specific immunological memory following the first confrontation with a microorganism. Memory T cells are capable of responding rapidly upon subsequent exposure to the same microbes thus providing protective immunity. This proposal aims to investigate how cytotoxic T cells establish memory following their primary encounter with microorganisms. The proposal will dissect the relationship between memory T cell formation and the amoun ....The hallmark of the adaptive immune response is the development of specific immunological memory following the first confrontation with a microorganism. Memory T cells are capable of responding rapidly upon subsequent exposure to the same microbes thus providing protective immunity. This proposal aims to investigate how cytotoxic T cells establish memory following their primary encounter with microorganisms. The proposal will dissect the relationship between memory T cell formation and the amount-length of antigen exposure; and the influence on memory induction from various immune modulators (cytokines) at the time of antigen encounter. Using a range of sophisticated detection methods, very early memory T cells will be identified in the primary response and tracked through their differentiation into long-term memory pool. Experiments will determine how T cells against particular determinants are selected from the primary immune response, retained in the memory pool and recalled in the subsequent challenges. The properties of antigen processing of various determinants will be correlated with the immunodominance hierarchy in the primary and memory response. Taken together the proposed project is central to understanding how memory T cells are created and what rules govern their stability. The project is highly relevant to vaccine design against tumours and pathogensRead moreRead less
Regulation Of Tissue-Resident Memory T Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$494,554.00
Summary
A recently identified subset of T cells that reside in the skin are critical to combat viral infection. However, little is known about how these T cell populations are formed. This project will characterise the pathways required to generate these cells and will identify novel factors that regulate their development. A greater understanding of how these T cells can be generated will open the way to utilise these cells in new vaccine strategies.
Viral Antigen Presentation Kinetics And Memory T Cell Inflation
Funder
National Health and Medical Research Council
Funding Amount
$503,753.00
Summary
The ageing of the population is one of the major transformations being experienced by Australia’s population which will have major health implications. Recent studies have shown that many elderly individuals display ‘immune risk phenotype’ (IRP) which is characterised by a severely distorted immune system and human cytomegalovirus (CMV) infection. In this project we will investigate the mechanisms by which CMV alters cellular immune system and thus impacts on the host immunity against other path ....The ageing of the population is one of the major transformations being experienced by Australia’s population which will have major health implications. Recent studies have shown that many elderly individuals display ‘immune risk phenotype’ (IRP) which is characterised by a severely distorted immune system and human cytomegalovirus (CMV) infection. In this project we will investigate the mechanisms by which CMV alters cellular immune system and thus impacts on the host immunity against other pathogens.Read moreRead less
Lodging Resident Memory T Cells Along The Respiratory Tract As An Approach To Protect Against Influenza Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$626,555.00
Summary
We have developed methods to deposit highly protective influenza fighting cells along the respiratory tract and we will apply these principles to develop better influenza virus vaccines
Priming, Recruitment And Retention Of Influenza Virus Specific CD8 T Cells In The Upper Airways
Funder
National Health and Medical Research Council
Funding Amount
$633,371.00
Summary
Influenza virus gains entry into the body by inhalation and initiates its replication cycle within the upper airways. This early stage of infection, when the amount of influenza virus is low, provides the ideal window of opportunity for an effective immune response to limit disease progression. In this proposal we will define the immunity that can be evoked within the upper airways and determine immune mechanisms left behind that can safeguard this region from this important respiratory pathogen
Molecular Pathways That Control Differentiation And Function Of Tissue-resident Memory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$890,636.00
Summary
T cells residing in organs such as gut, liver or skin guard against infection and are critical for preventing tumour development. We found that the combined activities of two factors, Blimp1 and Hobit, are critical for the development of these so-called tissue-resident T cells. Using a series of new tools, we will identify how the molecular network required for the development of tissue-resident T cell is established. This may allow us to harness their critical functions in therapy.