Many white blood cells have an innate ability to sense infection, and trigger inflammation to fight invading microbes. These innate immune cells use particular receptors to sense pathogens and we have now identified a new pathway that leads to the activation of one of these, known as Pyrin. Genetic mutations can activate this pathway, and our project will determine the molecular basis for this, and how it can be targeted to treat inflammatory disease.
The Role Of Perivascular Macrophages In The Regulation Of Skin Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$616,518.00
Summary
Neutrophils are key defenders against bacterial infections. In this application we will test the hypothesis that perivascular macrophages play a critical role in the recruitment of neutrophils to site of cutaneous infection, and that these cells are targeted and destroyed by bacterial virulence factors. Our studies will gain novel insight into the leukocyte homing paradigm and shed new light on the mechanisms of microbial immuno-evasion.
Age-dependent Regulation Of Type 2 Immunity By Dermal Innate Lymphoid Cells
Funder
National Health and Medical Research Council
Funding Amount
$609,281.00
Summary
Type 2 immune responses are critical for the defense against worm infections, but can also cause allergic reactions. How type 2 immunity is regulated is poorly understood. The aim of this application is to define the function of a newly discovered skin immune cell population, dermal type 2 innate lymphoid cell, in cutaneous worm infections and allergies. We anticipate that our studies will aid in the development of strategies to prevent or treat skin allergies and parasitic infections.
Mammals have evolved an array of mechanisms to sense microbes. These immune sentinels must distinguish self from non-self to activate an immune response. The initiation, amplification and quenching of an immune response is carefully orchestrated to eliminate invading pathogens while minimising collateral damage to host tissues. This research focuses on proteins that prevent inflammatory diseases such as cardiovascular disease, hepatitis, inflammatory bowel disease and skin diseases.
Initial Interactions Of Herpes Simplex Virus With Innate Immune Cells In Human Skin
Funder
National Health and Medical Research Council
Funding Amount
$522,589.00
Summary
Herpes simplex viruses 1 and 2 cause widespread and occasionally serious diseases including genital herpes, neonatal death and encephalitis. Current vaccine candidates are at best partially effective. This grant will examine the way that the virus enters, initially spreads within the skin and interacts with immune cells to help determine which cells should be stimulated by vaccines.
Defining The Role Of Nlrp1 And The Inflammasome In Host Defence And Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$634,459.00
Summary
The immune system protects the body from invading pathogens, but it can also attack the body causing inflammatory and autoimmune diseases like arthritis and multiple sclerosis. This project will focus on the molecular regulation of the ïinflammasomeÍ, a protein complex that senses invading pathogens and triggers the immune response. Understanding the inflammasome may hold the key to a better understanding of how the good and bad functions of the immune system can be balanced to prevent disease.
Mechanisms Of Immune-evasion By Group A Streptococcus During Skin Infection
Funder
National Health and Medical Research Council
Funding Amount
$602,609.00
Summary
Infections by Group A Streptococcus (GAS), or Streptococcus pyogenes, represent a global health concern. Currently no vaccine exists against GAS thereby mandating a better understanding of the immune response against the bacterium. Using in vivo microscopy, the aim of this proposal is to dissect in real time how neutrophils detect and destroy GAS following skin infection, and how the bacterium manages to circumvent the attack by innate immune cells.
Understanding The Role Of MAIT Cells In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$547,593.00
Summary
A specialised set of T lymphocytes called Mucosal Associated Invariant T (MAIT) cells protect us from bacteria and yeast at mucosal sites where the body's immune defences are most easily breached, e.g. gut, oral cavity, airways & reproductive tract. This study investigates the role of MAIT cells in health and in diseases like inflammatory bowel disease, peptic ulceration, periodontitis and tuberculosis. Controlling MAIT cells could help in treating these conditions.
Control Of Combined Simian-human Immunodeficiency Virus Infection Utilising NK Cells Mediating Antigen-specific Antibody Dependent Cellular Cytotoxicity - A Novel Vaccine Modality
Funder
National Health and Medical Research Council
Funding Amount
$432,587.00
Summary
Recently, progress was made in developing a vaccine against HIV. Our laboratory was selected to join a global collaboration trying to elucidate the key to this success. Attention has focused on non-neutralizing antibodies and our laboratory has developed a unique expertise in detecting such immune responses. This research will define, purify and manufacture these antibodies and test their ability to prevent HIV in animals with the ultimate aim of producing a vaccine for human use.