Tumour B-cells From Lymphomas Are Resistant To ATP-mediated Apoptosis Due To Non-functional P2X7 Receptors
Funder
National Health and Medical Research Council
Funding Amount
$226,320.00
Summary
Adenosine triphosphate (ATP) is an important constituent normally present inside cells. When added to normal lymphocytes (or released by cells lining the vessel wall or in lymph nodes), ATP acts from outside these cells to open a pore as well as activate an enzyme which digests the lipid envelope of the cell. This loss of lipid covering of the cell produces a leakiness to various constituents of the cell which gradually leads to death of normal lymphocytes. However in the malignant lymphocytes o ....Adenosine triphosphate (ATP) is an important constituent normally present inside cells. When added to normal lymphocytes (or released by cells lining the vessel wall or in lymph nodes), ATP acts from outside these cells to open a pore as well as activate an enzyme which digests the lipid envelope of the cell. This loss of lipid covering of the cell produces a leakiness to various constituents of the cell which gradually leads to death of normal lymphocytes. However in the malignant lymphocytes of human lymphomas this mechanism of cell death does not operate. The loss of function of this 'death receptor' explains why in the lymphomas there is a progressive accumulation of malignant lymphocytes which give enlargement of lymph nodes and spleen and leads to death of the patient. Knowledge of the defect in this pathway of cell death will enable new strategies to be introduced to control this malignant disease.Read moreRead less
Mechanisms For The Development Of Leukaemia Via Antibody Hypermutation
Funder
National Health and Medical Research Council
Funding Amount
$82,421.00
Summary
During responses to infection, the antibody genes in responding B cells mutate at a high rate, resulting in B cells producing better antibodies. Although essential for long-lived immunity, antibody mutation involves the introduction of DNA breaks which can occasionally cause leukemia or lymphoma. We understand only poorly how DNA repair systems normally make sure that antibody mutation is benign and does not cause cancer.
Determining The Molecular Basis Of Therapy Resistance Conferred By Genetic Lesions In The Tumour Protein TP53 In Haematological Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$885,183.00
Summary
Blood cancers that have genetic lesions in a tumour suppressor protein called TP53 respond poorly to therapy. Curing these patients is extremely challenging and new therapeutic strategies are desperately needed. Here, we aim to uncover the molecular mechanisms of drug resistance caused by loss of TP53 function and rationally design new therapies that may be curative. To do this, our team of leading scientists and clinicians will study patient samples and pre-clinical models of blood cancer.
Physiologic And Aberrant DNA Recombination In B Lymphocytes
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
B cells produce antibody which is critical to fight infection. In order to perform this function, antibody genes must first be modified by immune enzymes. However, abnormal DNA attack by these enzymes outside of antibody genes can result in B cell cancer. How the immune system detects and destroys cancerous B cells is poorly understood. This research will provide insight into these processes, and in doing so will further our understanding of how B cell cancers develop and how they are destroyed.
The Regulation And Differentiation Potential Of Human Memory B Lymphocytes
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Antibody produced by our immune system plays a critical role in protecting us from infectious disease. Remarkably our ability to make antibodies is much faster the second time we see the infection. This memory of the previous attack occurs due to the formation of memory B cells that circulate in the blood, sometimes for years, looking for the same intruders. If they detect the infection they rapidly become activated and remake the antibody. These memory cells are very important for our protectio ....Antibody produced by our immune system plays a critical role in protecting us from infectious disease. Remarkably our ability to make antibodies is much faster the second time we see the infection. This memory of the previous attack occurs due to the formation of memory B cells that circulate in the blood, sometimes for years, looking for the same intruders. If they detect the infection they rapidly become activated and remake the antibody. These memory cells are very important for our protection. Vaccines operate by tricking the immune system into making these memory cells, even though the body hasn't seen the actual disease. Although clearly vital for our health little is known about the activation and antibody production by human B memory cells. This project will redress our lack of knowledge by performing a comprehensive evaluation of the properties of this important cell type.Read moreRead less
Absence Of CC Chemokine Receptor 6 Dysregulates The Humoral Immune Response.
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
The individual steps leading to the activation and differentiation of B cells and the formation of mature functional germinal centres have been investigated in detail and are well understood. In contrast, the underlying molecular signals, which regulate the different events and prevent either autoimmunity or immunodeficiency are still not fully comprehended. This proposal will address these regulatory steps that prevent autoimmunity.
I am an Immunologist interested in the role of B-lymphocytes, their survival and expression of a novel chemoreceptor in Autoimmunity. I also study the important role of Neuropeptide Y in modulating key immune functions.