The hypothesis at the root of this study is that a healthy immune system will recognise a cell when it becomes malignant and destroy it thus preventing the growth and spread of cancer. Therefore cancer can only occur when this process goes wrong. If we could find out how the immune system interacts with cancer cells and what abnormalities are occurring in this interaction we may then be able to develop strategies to improve the immune response to cancer. This would represent a potentially novel form of treatment and would be expected to improve the response to vaccination therapies that are already undergoing clinical trials in some cancers. This study will look at T cell function in blood samples from patients with leukaemia and lymphoma and then go on to look at mechanisms of improving that function in a mouse model. Finally, attempts will be made to generate a patient tumour-specific T cell response in vitro using the information gained in the earlier parts of the study. This research will be carried out by a clinical research fellow in the Institute of Cancer, Charterhouse Square, London.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Have you ever wondered why your hands are the size they are? Or why some people have bigger hands, but they are almost identical in shape and proportion to your hands? The control of organ growth is highly complex, but highly important, as when the control system fails, we get overgrowth, and frequently cancer. How does the organ know when to stop growing? How does it control its shape? If we can understand this, perhaps we will be able to understand what happens when tissues over grow, and treat the problem (e.g. cancer) at its source. Many biologists have successfully used the Drosophila wing as a model to study growth control, revealing many parallels to human growth control. I hope to put all these data, the pieces of a puzzle, together, into a mathematical/computer model and eventually make a virtual wing. I‘ll be able to compare the relative importance of the different control mechanisms, something that‘s quite hard to do via experiments. I may find that internal control is key, and the environment plays little role, or vice versa. I can also model different cancerous conditions, and quickly test treatments before deciding whether they are worth trying experimentally/clinically.

To achieve productive infection, HIV must insert a DNA copy of its genome into a chromosome of a human cell. This complex process is orchestrated by integrase, an enzyme carried by the virus. Once integration is complete, the viral genome becomes a permanent resident in a cellular chromosome. From there it will initiate production of new infectious particles or it might stay dormant and undetected for a long period of time. The integration is partly responsible for the notable persistence of retroviral infections. Yet, the dependence of HIV on integration is also an exploitable weakness. A new class of drugs, disrupting enzymatic activity of integrase, called strand transfer inhibitors, takes advantage of this weakness to fight HIV infection. The three-dimensional atomic structure of HIV integrase is not known and even less understood is the architecture of its active form during integration process. Currently, the lack of structural information is the major impediment to the development of strand transfer inhibitors. This project aims to elucidate the three-dimensional structure of integrase. We will determine atomic structures of this protein separately and in active, DNA-bound, form. To achieve our goals we will use X-ray crystallography, which allows visualization of protein molecules, although requiring a significant amount of preparatory work. In particular, to determine high-resolution structures, we will have to obtain crystals of integrase in complex with accessory proteins and/or DNA. Our results will be published in open access journals and the data will be accessible to the scientific community via public databases. Our research will generate dat, which will be of great value for drug discovery by both academic and private groups, and will serve to reduce the costs and improve availability of the eventual treatments.