Upregulation Of Chemokine Receptor Expression And Function On CD4+ T Cells In Primary And Secondary Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$469,500.00
Summary
This research will begin to determine the significance of changes in the amount of recently-discovered proteins on the surface of cells called T lymphocytes. These cells control immune responses and move throughout the body to do this. Sometimes, they are activated inappropriately and cause diseases like asthma, arthritis and multiple sclerosis and other times they need assistance for activation (vaccination). It is therfore important to understand how the movement of these cells through the bod ....This research will begin to determine the significance of changes in the amount of recently-discovered proteins on the surface of cells called T lymphocytes. These cells control immune responses and move throughout the body to do this. Sometimes, they are activated inappropriately and cause diseases like asthma, arthritis and multiple sclerosis and other times they need assistance for activation (vaccination). It is therfore important to understand how the movement of these cells through the body is controlled. A better understanding of this process shuld allow us to design better ways to control it, thereby controlling the negative aspects of T lymphocyte activation.Read moreRead less
Investigation And Therapeutic Targeting Of The Immune Mechanisms That Predispose To And Increase The Severity Of Influenza In Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$326,097.00
Summary
In pregnancy there is suppression of maternal immunity to enable fetal implantation and growth. Respiratory viruses, like influenza, take advantage of these changes and cause infections that are more severe in pregnant women, affecting them and their babies. In this project we aim to identify specific immune responses against viruses that are reduced in pregnancy that can be selectively boosted. This has the potential to protect against viruses without affecting the pregnancy or baby.
Targeting Caspase 8 In T-Cell Homeostasis And Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,215,780.00
Summary
Chronic infectious diseases such as HIV, hepatitis B and tuberculosis impose a massive global health burden and new treatments are desperately needed. This proposal investigates a new approach to improve immune responses and clear chronic infections. Our multidisciplinary team will define the molecular and cellular biology underlying this approach and translate our findings by re-purposing a drug already approved for other indications in humans.
Investigating The Mechanism And Consequences Of Cytotoxic Lymphocyte Detachment
Funder
National Health and Medical Research Council
Funding Amount
$419,180.00
Summary
Killer cells are white blood cells that destroy cancerous cells. To move to their next target they must quickly detach from a dying target. Failure of detachment results in excessive inflammation and tumour escape. This project will discover the detachment signals required to ‘release’ a locked-on killer cell. This will lead to a deeper understanding of immune pathology and new ways of treating cancer.
VITAL: Vaccine Immunomodulation Throughout The Aging Lifespan
Funder
National Health and Medical Research Council
Funding Amount
$795,117.00
Summary
The elderly respond less well to vaccines than their younger counterparts. Flu is particularly dangerous to the elderly. In this proposal we will determine the likely immune mechanism undelying this difference, as well as specifically address the urgent issue of whether prior injection with a whooping cough vaccine makes Flu vaccines less likely to be effective.
Innate lymphoid cells (ILCs) are found in the lining of the intestine and are part of the intricate crosstalk between the food we eat, good bacteria, epithelial cells and other immune cells. Without ILCs, the body is susceptible to infections through the intestinal tract. I will investigate the signals from nerve cells that control that activity of ILCs during infection to give us insights into pathways that activate ILCs in situations where they are reduced or inactive.
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
Maintenance Of Regulatory T Cells During Inflammation And Tumor Development By IL-33
Funder
National Health and Medical Research Council
Funding Amount
$676,979.00
Summary
Regulatory T cells (Tregs) are required for preventing inflammation in tissues such as lung, fat and skin. We found recently, that the signalling molecule IL-33 is required for tissue Tregs and up-regulated during inflammation and tumor development. We therefore aim to determine the role of IL-33 in maintenance and function of Tregs and to identify molecular targets of IL-33 that may allow therapeutic targeting of Tregs in patients with inflammatory conditions or cancer.