Identifying The Ontogeny And Fate Of T Follicular Helper Cells By Two-photon Photoconversion
Funder
National Health and Medical Research Council
Funding Amount
$623,070.00
Summary
The aim of this proposal is to investigate immune cells called T follicular helper cells using a novel microscopy-based method that we have developed. This method lets us ‘tag’ these cells in a way that enables us to distinguish them from all other cells and follow them as they migrate to different immunological compartments during the response. T follicular helper cells are important for protective immune responses against pathogens and a better understanding of this T cell subset will aid vacc ....The aim of this proposal is to investigate immune cells called T follicular helper cells using a novel microscopy-based method that we have developed. This method lets us ‘tag’ these cells in a way that enables us to distinguish them from all other cells and follow them as they migrate to different immunological compartments during the response. T follicular helper cells are important for protective immune responses against pathogens and a better understanding of this T cell subset will aid vaccine design.Read moreRead less
Regulation Of T Cell Effector Function In Peripheral Tissues
Funder
National Health and Medical Research Council
Funding Amount
$698,550.00
Summary
Protection from infections relies on different types of immune cells. While some of these cells are found in the blood, others reside in peripheral tissues such as the skin. We will analyse the function of these peripheral immune cells to understand how they work to fight off infections. We will also investigate how so-called memory cells that permanently reside in peripheral tissues can protect from re-infection with similar bacteria or viruses.
We have identified a population of immune cells called ‘resident memory T cells’ that reside in tissues of the body. These resident memory T cells play an important role in controlling infections, but it is also apparent that they can lead to aberrant immune reactions, causing autoimmune diseases. This project aims to further our understanding of these immune cells, including how they can be identified and generated, and how they can be controlled to prevent disease.
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
Subset Determination Of Tissue-Resident T Cell Memory
Funder
National Health and Medical Research Council
Funding Amount
$473,394.00
Summary
Immunity relies on white blood cells called T cells that circulate around the body and which are also found permanently lodged at body surfaces. It is non-circulating T cells that are the most important in protecting against infection. In this application we propose to show that only a subset of T cells can form the resident population and to identify the molecules that determine T cell residency. This information can then be used for the efficient construction of disease preventing vaccines.
Immune Surveillance Of The CNS During Malaria Infection
Funder
National Health and Medical Research Council
Funding Amount
$617,857.00
Summary
Infections in the central nervous system (CNS) can have profound neurological complications. Neurological disease caused by cerebral malaria (CM) is a lethal complication in humans. We have established a new model of longitudinal imaging of T cell responses in the brain during experimental CM in mice infected with Plasmodium berghei ANKA. This project will investigate the mechanisms of CNS injury and provide fundamental information about T cell responses in the CNS during infection.
Using Single-cell Genomics To Resolve Functional Diversification By CD4+ T Cells In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$1,048,096.00
Summary
During immune responses, individual CD4+ T cells multiply and produce hundreds of descendants, with close relatives within a family often developing very different skills. How such differences emerge from one ancestor remains unclear. We use new methods to look at individual CD4+ T cells in unprecedented detail, allowing us to see how close relatives begin to grow apart. Using this, we hope to find novel ways of educating CD4+ T cells to prevent infectious and immune-mediated diseases.
Current vaccines rely on immune components in the blood. We are taking a different approach, which focuses on immunity at the body surfaces. These are the areas where pathogens first gain access to the body and we have shown that immune cells in these regions are far more potent than those that need to be recruited from the circulation.
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 body’s surfaces are continually under threat from microbes that may cause debilitating disease. Our ability to control such infections relies on our immune system, consisting of different cell types with specialised functions. We will study frontline immune cells that populate barrier tissues such as skin and mucosa where they provide enhanced local protection by responding vigorously on infection. Our studies will guide the development of future therapies harnessing our immune system.