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Structure And Interactions Of The Malarial Vaccine Candidate AMA1
Funder
National Health and Medical Research Council
Funding Amount
$351,000.00
Summary
Malaria remains one the most lethal infectious diseases in the world today. It is directly responsible for 1-2 million deaths annually, many of these in children under 5 years of age. More than 300 million clinical cases are reported annually and over 40% of the global population (in excess of 2 billion people) are at risk. There is an urgent need for a vaccine against this disease, particularly because of the recent increase in forms of the parasite resistant to many of the best anti-malarial d ....Malaria remains one the most lethal infectious diseases in the world today. It is directly responsible for 1-2 million deaths annually, many of these in children under 5 years of age. More than 300 million clinical cases are reported annually and over 40% of the global population (in excess of 2 billion people) are at risk. There is an urgent need for a vaccine against this disease, particularly because of the recent increase in forms of the parasite resistant to many of the best anti-malarial drugs. AMA1 is an asexual stage antigen and a leading vaccine candidate. Little is known about the function of this protein, but it has been proposed to play a role in invasion of red blood cells. A clearer understanding of the structure of parasite antigens such as AMA1 that induce a protective response in infected individuals would provide a stimulus to research into recombinant antigens as vaccines and a deeper understanding of host-parasite interactions. The aims of this project are to determine the three-dimensional structures of the three major structural domains of AMA1 and of the complete AMA1 antigen. We shall also determine the structures, both in aqueous solution and bound to AMA1, of small peptides identified by phage display as being capable of binding to AMA1 and blocking parasite entry into red blood cells. The overall goal of this work is to determine the structure of AMA1 and define the structural basis for its interaction with small peptides capable of blocking its activity as well as the structural features necessary for AMA1 to react with protective antibodies. The structure of AMA1 will provide a molecular basis for the design of engineered antigens capable of eliciting a protective immune response against AMA1. The inhibitory peptide structures will likewise provide a molecular basis for the design of non-peptidic blockers of AMA1. Either or both of these may be useful therapeutics leads in the fight against malaria.Read moreRead less
Differentiation of Cord Blood Stem cells into Thymus (T) cells with regulatory phenotype and function. This project will develop technologies for a stem cell therapy platform based on cord blood stem cells, to enable treatment of autoimmune diseases or transplants. Building on the University of Adelaide's frontier demonstration of differentiation of regulatory Thymus (T) cells from cord blood stem cells, the project will develop techniques to expand the numbers of T cells generated. This has the ....Differentiation of Cord Blood Stem cells into Thymus (T) cells with regulatory phenotype and function. This project will develop technologies for a stem cell therapy platform based on cord blood stem cells, to enable treatment of autoimmune diseases or transplants. Building on the University of Adelaide's frontier demonstration of differentiation of regulatory Thymus (T) cells from cord blood stem cells, the project will develop techniques to expand the numbers of T cells generated. This has the potential to maintain Australia's lead in differentiation of cord blood stem cells and to provide a significant breakthrough in potential treatments of autoimmune diseases (e.g. type 1 diabetes) or transplantation. These diseases affect both a healthy start to life and healthy ageing, and an Australian invention to treat or cure them would have global impact.Read moreRead less
MECHANISMS OF MOTILITY AND METASTASIS In BREAST CANCER
Funder
National Health and Medical Research Council
Funding Amount
$209,505.00
Summary
The broad aim of this proposal is to elucidate novel molecular mechanisms of breast cancer cell motility that are relevant to metastasis or the spread of cancer. The function of two genes will be studied. We propose that (1) reduced on-random motile (ROM) regulates the speed of cancer cell movement, and (2) Neural Wiskott-Aldrich syndrome protein (N-WASP) regulates the directional component of cell movement. We will relate the function of ROM and N-WASP to rapid, linear walking along collagen fi ....The broad aim of this proposal is to elucidate novel molecular mechanisms of breast cancer cell motility that are relevant to metastasis or the spread of cancer. The function of two genes will be studied. We propose that (1) reduced on-random motile (ROM) regulates the speed of cancer cell movement, and (2) Neural Wiskott-Aldrich syndrome protein (N-WASP) regulates the directional component of cell movement. We will relate the function of ROM and N-WASP to rapid, linear walking along collagen fibres in live tumours and to breast cancer metastasis to the lung. ROM will be inhibited in breast cancer cells and we expect increases in both the speed of cell movement and metastasis. Therefore, ROM functions as a suppressor of metastasis. Inhibition of N-WASP, however, is expected to compromise both the directionality of cell movement and metastasis. N-WASP is therefore, a promoter of metastasis. At the completion of this work, the regulatory mechanisms of motility and metastasis by ROM and N-WASP will be defined. This will facilitate the development of biologically targeted agents for ROM and N-WASP that can be used to control metastasis. In addition, these agents that target the motility pathway are appropriate for use in combined therapy with agents that target a different pathway such as survival or growth. This will significantly improve disease control rates or the proportion of patients with partial or complete disease regression. This proposal addresses the National Health Priority, cancer, and related National Research Priority, ageing well and ageing productively, where in the longer term, we will be able to create new and much needed therapy for metastasis.Read moreRead less