Novel Vitamin E Analogues with Enhanced Specificity for Malignant Cells. The aim of this project is to synthesise and characterise novel compounds based on vitamin E succinate that are capable of efficiently and selectively killing cancer cells. The new compounds will be tested for their ability to induce programmed cell death in cancer cells and the most active of them will be also tested for anti-cancer effect in a pre-clinical model. We believe that novel analogues based on vitamin E succinat ....Novel Vitamin E Analogues with Enhanced Specificity for Malignant Cells. The aim of this project is to synthesise and characterise novel compounds based on vitamin E succinate that are capable of efficiently and selectively killing cancer cells. The new compounds will be tested for their ability to induce programmed cell death in cancer cells and the most active of them will be also tested for anti-cancer effect in a pre-clinical model. We believe that novel analogues based on vitamin E succinate can lead to the discovery of very effcient and selective anti-cancer drugs with no side-effects that may be used for patient treatment in the future. This makes our project of exceptional significance.Read moreRead less
Functional characterisation of neurons derived from embryonic stem cells and NS cells. The ability to obtain specific neurons from NS cells will revolutionise the study of nerve function, will allow the establishment of much-improved models for discovery of new drugs, and will define how enriched populations of neural cells can be obtained for applications in treatment of neurodegenerative diseases. The project will provide vital data for the emerging biotechnology industry associated will appl ....Functional characterisation of neurons derived from embryonic stem cells and NS cells. The ability to obtain specific neurons from NS cells will revolutionise the study of nerve function, will allow the establishment of much-improved models for discovery of new drugs, and will define how enriched populations of neural cells can be obtained for applications in treatment of neurodegenerative diseases. The project will provide vital data for the emerging biotechnology industry associated will applications of stem cell biology, and will stimulate clinical researchers to investigate the therapeutic potential of cell derived from NS cells.Read moreRead less
Pancreatic Differentiation of Cord Blood Stem Cells using Smart Surfaces. Cord blood cells obtained at the time of delivery of a baby are a valuable resource that have the potential to develop into many cell types. This Project entails attaching stem cells derived from cord blood to appropriate 3 dimensional smart surfaces, and examining the ability of such cells to develop into insulin-producing cells. An understanding of how to coax stem cells, seeded on to smart surfaces, to develop into ma ....Pancreatic Differentiation of Cord Blood Stem Cells using Smart Surfaces. Cord blood cells obtained at the time of delivery of a baby are a valuable resource that have the potential to develop into many cell types. This Project entails attaching stem cells derived from cord blood to appropriate 3 dimensional smart surfaces, and examining the ability of such cells to develop into insulin-producing cells. An understanding of how to coax stem cells, seeded on to smart surfaces, to develop into mature cells with different functions will enhance our ability to understand how cells develop. As well, it enhance the potential usefulness of cord blood for research purposes. Read moreRead less
Novel compounds to disrupt protein-protein interactions. Many diseases involve aberrant interactions between proteins. Strategies to inhibit such interactions have potential as tool reagents for biological research but also as new therapies. Most drugs currently used in the clinic are small organic molecules, though these typically are not effective at disrupting protein complexes, hence alternatives are required. This proposal to examine foldamers as a novel strategy for inhibiting protein: pro ....Novel compounds to disrupt protein-protein interactions. Many diseases involve aberrant interactions between proteins. Strategies to inhibit such interactions have potential as tool reagents for biological research but also as new therapies. Most drugs currently used in the clinic are small organic molecules, though these typically are not effective at disrupting protein complexes, hence alternatives are required. This proposal to examine foldamers as a novel strategy for inhibiting protein: protein interactions could lead to the development of new drugs for the treatment of diseases where the current traditional approaches have proven ineffective.Read moreRead less
Intelligent scaffolds and methods for repair of osteochondral defects. Osteoarthritis (OA) produces articulation of bone against bone resulting in extreme pain and disability. Of all musculoskeletal disorders, osteoarthritis has the greatest social and economic implications worldwide. By 2030, it is projected that 9.3% of the adult population will suffer from arthritis, significantly affecting their quality of life and overall productivity. A tissue engineered product capable of repairing osteoc ....Intelligent scaffolds and methods for repair of osteochondral defects. Osteoarthritis (OA) produces articulation of bone against bone resulting in extreme pain and disability. Of all musculoskeletal disorders, osteoarthritis has the greatest social and economic implications worldwide. By 2030, it is projected that 9.3% of the adult population will suffer from arthritis, significantly affecting their quality of life and overall productivity. A tissue engineered product capable of repairing osteochondral defects that does not require revision over time but becomes fully integrated with the host tissue will have significant benefits. It will improve patient activity and quality of life, and significantly reduce current health care costs associated with osteoarthritis sufferers.Read moreRead less
How IGFBP-3 improves cancer cell responsiveness to DNA-damaging therapies. A protein called IGFBP-3 can modulate the way cancer cells respond to treatments such as radiotherapy and certain chemotherapy drugs. These therapies, which act by damaging cells' DNA, play an important role in the treatment of many cancers, but their effectiveness is limited by the ability of cells to oppose the treatment by repairing damaged DNA. This project aims to discover how IGFBP-3 acts to change cancer cells' res ....How IGFBP-3 improves cancer cell responsiveness to DNA-damaging therapies. A protein called IGFBP-3 can modulate the way cancer cells respond to treatments such as radiotherapy and certain chemotherapy drugs. These therapies, which act by damaging cells' DNA, play an important role in the treatment of many cancers, but their effectiveness is limited by the ability of cells to oppose the treatment by repairing damaged DNA. This project aims to discover how IGFBP-3 acts to change cancer cells' response to treatment, using breast cancer cells growing in culture as a model system. This work has the potential to lead to improvements in the treatment of cancer patients by increasing our understanding of what happens when cancer cells are exposed to radio- or chemotherapy.Read moreRead less
Mechanistic basis of a reproductive lesion in transforming growth factor beta-1 (TGFb1) null mutant mice. Null mutation in the gene encoding the cytokine transforming growth factor beta-1 (TGFb1) causes infertility in male and female mice. In recent experiments we have found that TGFb1 deficiency is associated with impaired ovarian and testicular steroidogenesis, arrested development of pre-implantation embryos and disrupted mammary gland morphogenesis. The aims of the current project are to un ....Mechanistic basis of a reproductive lesion in transforming growth factor beta-1 (TGFb1) null mutant mice. Null mutation in the gene encoding the cytokine transforming growth factor beta-1 (TGFb1) causes infertility in male and female mice. In recent experiments we have found that TGFb1 deficiency is associated with impaired ovarian and testicular steroidogenesis, arrested development of pre-implantation embryos and disrupted mammary gland morphogenesis. The aims of the current project are to unravel the mechanistic basis of the reproductive lesion in TGFb1 null mutant mice and to determine the effect of exogenous systemic delivery of TGFb1 in alleviating this lesion. It is expected that the project will provide new insight into key roles for TGFb1 in governing male and female fertility, and shed light on the prospects for exogenous supplementation of TGFb1 for improving reproductive performance in wild-type animals. This knowledge has potentially important applications in the livestock breeding industry, in devising novel contraceptive vaccine strategies, in the human pharmaceutical industry, and in devising novel contraceptive vaccine strategies.Read moreRead less