Understanding Universal Immunity To Influenza Viruses
Funder
National Health and Medical Research Council
Funding Amount
$687,975.00
Summary
A/Prof Kedzierska’s work combines cutting-edge basic research with unique clinical studies to define how to generate protective immunity against the pandemic and newly emerged influenza viruses. This research will identify key factors that drive the severe and fatal influenza disease in high-risk groups, including the young, elderly, pregnant women and Indigenous Austraians. Findings on the optimal human immunity to influenza viruses will be applicable to other infectious diseases and cancers.
Characterization Of MAIT Cell Function And Frequency At The Rectal Mucosa And Gastrointestinal Tract During HIV/SIV Infection
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
This project focuses on determining how HIV infection alters the function of rare, unconventional immune cell populations in the gastrointestinal tract. These cells are not well described in humans or primate models of HIV infection, but we will determine whether these cells are depleted by HIV infection and whether there are interventions that can boost the function of these cells in order better fight HIV infection.
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
Understanding Pathogenicity And Immunity In An Encephalitic Mouse Model Of Hendra Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$572,342.00
Summary
Our understanding of Hendra virus infection and immunity is extremely limited and has been hampered by a lack of appropriate animal models of disease and reagents. This Project will employ a newly-established mouse model to study encephalitis, the most life-threatening manifestation of this infection. We will use unique, state-of-the-art infrastructure and a plethora of mouse-specific reagents to investigate the mechanisms involved in regulating the host response to infection.
Antigen Presentation, Recognition And The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$15,738,750.00
Summary
The early events in immunity require various molecular interactions. We will examine the structural and biophysical basis for some of these interactions, including those associated with transplant rejection and autoimmunity. We will explore the impact of variation in immune response genes on immune evasion and disease susceptibility. Our basic research will determine the mechanisms by which the immune system discriminates between different self and micro-organism associated determinants. We will ....The early events in immunity require various molecular interactions. We will examine the structural and biophysical basis for some of these interactions, including those associated with transplant rejection and autoimmunity. We will explore the impact of variation in immune response genes on immune evasion and disease susceptibility. Our basic research will determine the mechanisms by which the immune system discriminates between different self and micro-organism associated determinants. We will address the structural and biochemical basis for operation of an immune molecule called tapasin and unravel the basis for how some viruses escape the function of this molecule, thus allowing their immune evasion. We will also explore the use of modified small proteins called peptides in a humanized model of gluten hypersensitivity resembling that of Celiac disease. The molecular basis of the natural human immune system's capacity to recognise and reject grafts will be examined. This complements work aimed at improving the prediction of clinical graft rejection in transplantation. Dendritic cells play a central role in immunity, responsible for capturing material, whether from micro-organisms or self tissues, and presenting it to cells of the immune system. Our program will study the development and immunological function of the different dendritic cell subtypes. We will determine the relative contribution of each to the maintenance of immune tolerance and to the induction of immunity to several pathogens, including herpes simplex virus and malaria. Novel dendritic cell surface molecules that we have discovered will be tested for their ability to enhance the effectiveness of vaccines. Overall, this program utilises a broad array of immunological techniques designed to dissect the development and function of various immune system cell types and determine the structure-function relationships between important cell surface molecules involved in immunity.Read moreRead less