Structure And Interactions Of A Disordered Malaria Surface Protein: Implications For Antigenicity
Funder
National Health and Medical Research Council
Funding Amount
$511,020.00
Summary
Malaria is responsible for around 2 million deaths annually, many in children under 5 years of age. Merozoite surface protein 2 (MSP2) from Plasmodium falciparum is being developed as a vaccine candidate. We will investigate the structure of MSP2 in various environments, including when bound to inhibitory antibodies. Key goals are to understand how the disordered structure of MSP2 affects its interaction with the host immune system and how that information can be used to design better vaccines.
High-affinity Protease-resistant Analog Of Insulin-like Growth Factor Binding Protein-2: Potential Cancer Co-Therapeutic
Funder
National Health and Medical Research Council
Funding Amount
$294,423.00
Summary
In many human cancers, including prostate and breast cancer, serum levels of insulin-like growth factor (IGF)-II are elevated, and this growth factor has been strongly implicated in promoting the progression of these tumours. The action of IGF-II in stimulating tumour growth is mediated through Type 1 IGF receptors on the surface of the cells. The IGF binding protein, IGFBP-2, has been shown to increase the action of IGF-II in some cancer cells in vitro. by binding to the outside of the cells as ....In many human cancers, including prostate and breast cancer, serum levels of insulin-like growth factor (IGF)-II are elevated, and this growth factor has been strongly implicated in promoting the progression of these tumours. The action of IGF-II in stimulating tumour growth is mediated through Type 1 IGF receptors on the surface of the cells. The IGF binding protein, IGFBP-2, has been shown to increase the action of IGF-II in some cancer cells in vitro. by binding to the outside of the cells as an IGF-II-IGFBP-2 complex and then presenting the IGF-II to the receptor by a process of sustained release. We propose to produce a very high affinity form of insulin-like growth factor binding protein-2 (OOptimised IGFBP-2O) which will sequester the IGF-II and effectively prevent it from binding to the receptor or the native IGFBP-2. We shall also engineer the OOptimised IGFBP-2O so that it is unable to bind to the outside of the cells. With this novel peptide, OOptimised IGFBP-2O, we will test the hypothesis that the growth of insulin-like growth factor (IGF)-dependent tumours can be arrested by preventing the localisation and presentation of IGF-II to IGF receptors. We expect that the availability of such a sequestering agent for IGF-II will increase the effectiveness of current cancer chemotherapy agents since it is known that IGF-II can help save cancer cells from chemotherapy-induced death.Read moreRead less
Dynamic Imaging Of The Immune Response In Lymph Nodes By Two-photon Microscopy
Funder
National Health and Medical Research Council
Funding Amount
$79,514.00
Summary
Despite the enormous contribution of vaccination to the prevention of human disease and suffering, little is known about the laws that govern the selection and survival of B cells during the response to infection or vaccination. Our research projects aim to integrate several cutting-edge technologies, including two-photon microscopy, in order to understand the cellular and molecular basis of immunity.
This Program Grant brings together a world-leading team of experts to elucidate mechanisms that protect most people from infection by making antibodies, and their failure caused by genes or infections like influenza or HIV. The team will determine mechanisms that protect most people from making antibodies against normal parts of our body, whose failure causes numerous autoimmune diseases including rheumatoid arthritis. The team will develop ways to engineer better antibodies.
Epigenetic Mechanisms That Regulate B Cell Differentiation And Memory B Cell Persistence To Provide Long-term Immune Protection
Funder
National Health and Medical Research Council
Funding Amount
$318,196.00
Summary
Memory immune cells remember antigens that have previously induced an immune response, and the ability of these cells to rapidly clear pathogens has led to successful vaccination programs. This project will study epigenetic changes during the formation of immune memory that results in protection against foreign antigens. Understanding these processes will assist in creating more effective vaccines and treatments for patients with immune disorders.
Defining The Stage Specific Requirements For Bcl-2 Family Members In The Development And Maintenance Of B Cell Memory
Funder
National Health and Medical Research Council
Funding Amount
$632,438.00
Summary
Both vaccinations and pathogenic infections provoke an immune response. Our immune system ñmemorizesî this response, enabling a faster and stronger reaction upon re-encounter. This memory requires specialized cells of the immune system, some of which secrete antibodies and some of which patrol the body. Remarkably, these cells can live for decades in humans and provide immunity. In this project we will study the roles of specific proteins regulating the generation and survival of memory cells.