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
To understand the genetic basis of two of the most important cancers in women, breast and ovarian cancer. The team has already identified one gene that confers a very high risk of breast cancer and may account for a large proportion of 'familial' breast cancer. Their aim is to identify additional predisposition genes and to determine their normal function in the cell, as well as the way in which they contribute to the development of cancer
Antibodies are made by B-cells and are essential for a functional immune system. B cells circulate in the body, and, when they encounter an invader, they mature into antibody-producing cells (ASC). A small proportion of the cells become “memory” cells with the potential to become ASC should the same infection occur in the future. This is the basis of vaccination. This program aims to understand how a B cell changes into an ASC. We aim eventually to be able to improve vaccines and understand dise ....Antibodies are made by B-cells and are essential for a functional immune system. B cells circulate in the body, and, when they encounter an invader, they mature into antibody-producing cells (ASC). A small proportion of the cells become “memory” cells with the potential to become ASC should the same infection occur in the future. This is the basis of vaccination. This program aims to understand how a B cell changes into an ASC. We aim eventually to be able to improve vaccines and understand diseases such as allergy, lupus, arthritis and leukaemia to develop novel therapies.Read moreRead less
Breast Cancer is a very common disease in women and although huge progress has been made in the last two decades, much remains to be done to improve our understanding of different types of breast cancer and its management. This program brings together the expertise of three senior researchers: 2scientists and 1 medical scientist. Dr Trench has an interest in identifying genes involved in cancers arising in patients who have a strong family history. She will use molecular methods and cohorts of p ....Breast Cancer is a very common disease in women and although huge progress has been made in the last two decades, much remains to be done to improve our understanding of different types of breast cancer and its management. This program brings together the expertise of three senior researchers: 2scientists and 1 medical scientist. Dr Trench has an interest in identifying genes involved in cancers arising in patients who have a strong family history. She will use molecular methods and cohorts of patients enrolled with Kathleen Cunningham Foundation for Research into Familial Breast and Ovarian Cancer to identify the genes responsible, assess their distribution in the population and determine whether these genes also play a role in non-familial cancers. Dr Khanna's work examines the complex array of enzymes that are responsible for maintaining the integrity of the DNA, and investigates how failure of these mechanisms leads to damage of the genetic material which ultimately results in cancer. It is known that genes involved in familial predisposition code for proteins that work as DNA repair enzymes. It is also known that different types of breast cancer exist, each with differing behaviour and response to treatment and that they are associated with specific genetic changes, including those associated with a familial predisposition. Prof Lakhani's interest lies in using microscopy and the latest molecular tools to refine the classification of these different types of breast tumour so that they can be managed appropriately by his surgical and oncological colleagues. A better understanding of the genetic changes and underlying biology of different types of breast cancer will lead to individualised and specific therapy for patients. This program brings together a unique combination, nationally and internationally, that investigates cancers at the level of genes and cells and translates the information to the clinic for the benefit of patient management.Read moreRead less