In 2002 the UK Government established that a Bank of human embryonic cell lines should be established to oversee the use of these cells to ensure that any cells of this type, used in the UK were obtained ethically and only used in research for the benefit of treatment of serious human disease. In addition the Bank should provide access to quality-controlled stocks of these cell lines to provide a high quality international resource in support of the UK s stem cell community and to further the use of these cells in regenerative medicine. Such a role for the Bank in supporting the move of stem cell therapies from the laboratory to the bedside was confirmed to be a key element in the UK Stem Cell Initiative Report prepepared by Sir John Pattison and accepted by the Government. In the next phase of funding (Phase III) the Bank aims to sustain and develop its position as the foremost repository of ethically-sourced and well characterised stocks of human stem cell lines banked to international quality standards. Whilst in Phase II the primary focus of the Bank was on academic research, Phase III will see the Bank coordinating more closely with scientific programmes translating research developments into therapeutic applications, the regenerative medicine clinical community and those developing human cell culture models to improve the efficiency of development of new drugs to reduce costs and increase patient safety. The Bank will continue to develop its international role in supporting the development of stem cell therapy through: ? the provision of quality-assured and safety tested cell lines and other products supporting researchers and clinical applications; ? its continued lead on best practice and the setting of international consensus standards for the delivery of high quality and safe stem cells; ? its developing training programme for stem cell scientists, technical staff and quality assurance personnel in support of the UK s developing regenerative medicine industry; ? its scientific collaborations and internal research programme to establish robust methodologies for cell expansion, differentiation, preservation and characterisation which will improve the qulity of materials supplied for research and provide improved methodological approaches for clincial application. It is intended that the Bank will now implement its position as a national resource and international centre of expertise in support of the development of regenerative medicines and product safety in the UK.

There is an urgent need for an effect vaccine to prevent serogroup B meningococcal disease. This causes about 1200-1500 cases of disease with about 100 deaths per year in the UK, with many more deaths worldwide. To date scientists have not been able to develop a vaccine that can protect against all the strains that cause disease. This vaccine, based on heat shock protein complexes presents a wide range of parts of the bacterium to the human immune system in a very effective way, offering the potential for cross strain protection. This proposal is to develop a manufacturing process for the vaccine so it can be made in the quantity and manner to be suitable for injection into large numbers of children.

Vaccination against typhoid fever is well established and is now being implemented as a control measure for this major human disease. Paratyphoid fever, an indistinguishable disease, however is not covered by this vaccine and there is a danger that paratyphoid may replace typhoid fever. This is of particular concern because the bacterial cause, Salmonella Paratyphi A, has become resistant to all but one of the antibiotics available for treatment, including fluoroquinolones such as ciprofloxacin. Several reports from India and the Far East describe cases of paratyphoid fever resistant to ciprofloxacin, the main drug for treatment. We propose to examine in detail the development of resistance to ciprofloxacin in S. Paratyphi A as it emerges. This information will increase awareness among clinical practitioners about resistant strains and so allow patients to be treated appropriately and enhance our understanding of the fundamental process of acquisition of antibiotic resistance in pathogenic bacteria. Resistance to antibiotics is a major threat to modern medicine, and because isolates of S. Paratyphi A are very similar; only five genes differ between the two isolates sequenced. The development of resistance in S. Paratyphi A therfore provides an ideal opportunity to study the evolution of resistance in bacteria. By recreating the natural mutations in laboratory strains of S. Paratyphi A we hope to observe the effects of each mutation on fitness as well on the resistance phenotype.

Cervical screening (the ‘smear test’) helps prevent cervical cancer by finding early signs of abnormalities that can be dealt with before they progress to cancer. Another way to prevent disease is to block infection by the human papillomavirus (HPV) types that can lead, usually after many years, to the development of cervical cancer. Vaccines are available that protect women from two of the most common types of HPV which should lead to a reduction of about 70% of cervical cancers. However, as there are other HPV types that also cause cervical cancer it will be necessary to maintain the cervical cancer screening programme, a significant recurrent investment by the NHS, to protect the UK population from this devastating disease. In this study, we will examine the antibodies produced by animals and humans in response to HPV immunisation and work out how effective the vaccines are against other types of HPV. This information will be used to map the relationships between HPV types and help predict what will happen to each HPV type when the population is vaccinated. We will also use this model to describe potential gaps in protection that can be filled by the next generation of vaccines. This information may also help to target limited NHS resources to those individuals who may not be sufficiently protected by vaccination.

Resistance to antimicrobials (eg antibiotics) is a significant health problem and is driven by antimicrobial prescribing patterns. The majority of antimicrobial prescribing for humans in the UK is by GPs, but efforts to change prescribing patterns have so far met with limited success. A R+D collaboration is to be established between the key functions of the Health Protection Agency and 3 Universities with complimentary expertise relevant to improving antimicrobial prescribing in primary care. The collaboration will achieve its objectives via 4 mechanisms: - ensuring that best practice guidance on antimicrobial prescribing is available to GPs and other primary care staff and regularly updated. - ensuring that best practice on how to change prescribing in primary care is identified, publicised and regularly updated. - developing and establishing a system for routinely monitoring antimicrobial prescribing in primary care to assess implementation of recommendations and to act as a tool for furure research. - acting as a focus for further research bids in this area. This bid is for a project manager to implement the collaboration and organise bids for funding to develop the 4 strands of work.