There are currently heightened public concerns over infection rates in UK hospitals, and in particular those caused by so called ?superbugs? that have become resistant to available antibiotics. One such bug is Clostridium difficile. It causes debilitating diarrhoea, which in extreme cases can kill. It mainly affects the elderly. As this proportion of the population is increasing, the disease is becoming more common. Worryingly, a new, even more deadly variant has now arrived in Europe from North America. Aside from the human suffering, it costs the NHS over #402 million per year, and now is responsible for more deaths per year than MRSA. To control infections, we need to understand how an organism causes disease. Under Wellcome Trust sponsorship, the complete genome sequence of the organism (ie., its genetic blueprint) has been determined. However, whilst we now know the sequences of every gene in the C. difficile chromosome, we do not understand what they are doing. The best way of working out what genes do, is to mutate them (make them non-functional) and assess the consequences. Until now this has not been possible. We have now developed the tools needed, and wish to use them to better understand how this bug causes disease. This should eventually lead to better ways of controlling the disease.

The EPSRC and SFI in Sustainable Chemistry - Atoms to Products (A2P) CDT is a four-year programme that provides advanced training and education to students, to prepare for rewarding careers in academia, industry and related sectors. The first-year training framework involves Core training attended by all students and Theme-specific training activities, where the students work as teams in one of four contemporary research themes (which are likely to change each year), supervised by several academic staff and industry scientists. During the first year, the students will select and develop their research projects and the details of the project will be fully known by the end of the year 1. CDT Research Theme: H2P - Heat to Power

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

Chemotherapy and radiation therapy are commonly used to treat melanoma. However many melanomas are resistant to such treatments because the cancer cells are able to counteract the effects of therapy by utilising the DNA repair machinery to repair DNA damage induced by these agents. The focus of my research is to develop drugs to block DNA repair in cells and thereby enhance cancer cell death. This will lead to better response to treatments and improve patient outcomes. My research will focus on APE1, an essential protein involved in DNA base excision repair. The host laboratory has developed compounds that can inhibit APE1 and I will evaluate the effects of these compounds in melanoma. In addition I will study the biological function of APE1 in melanoma by manipulating APE1 gene expression in melanoma using a variety of techniques. The proposal brings together leading research groups with complementary expertise to find new ways of treating melanoma.

The applicant will continue to support public engagement in science through similar methods to those previously used by the applicants research group. These include presentation at appropriate meetings open to the lay public (eg research charity annual meetings for stakeholders), media presentation (this has included ITV regional news, BBC24, BBC regional news, local and national newspapers) and web based information using the new University of Nottingham portal (active from autumn 2004). The applicant has written a number of articles aimed at lay audiences for both local and national journals and magazines (eg the Asthma Journal) and has appeared on regional radio telephone answer slots. The applicant s group has also hosted students considering a career in science (eg we hosted 2 Nuffield bursary students in 2004).