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Paterson Institute for Cancer Research Scientific Report 2009 Cover Images Paterson Institute for Cancer Research Scientific Report 2009 Cover images Top Mitotic BPAE cells in anaphase. F-actin is labelled with Texas Red-x phalloidin. Microtubules, in green, are la - belled with mouse anti- α-tubulin BODIPY FL goat anti- mouse IgG. Blue nuclear staining with DAPI. Imaged on the Spinning Disk Confocal microscope. Image provided by Achille Dunn, Advanced Imaging Fa - cility. Bottom Immunostaining demonstrating blood vessels surrounding a tumour. Glut1 immunostaining (red) specifically labels veinous structures whereas arterial structures are Glut1 negative. Red blood cells in the vessels were detected by inherent autofluorescence (green) and cell nuclei were labelled with DAPI (blue). Image provided by Darren Roberts, Clinical and Exper - imental Pharmacology Group. Scientific Report 2009 Paterson Institute for Cancer Research Contents Director’s Introduction 5 Georges Lacaud 38 Stem Cell Biology Group Research Highlights 8 Valerie Kouskoff 40 Stem Cell and Haematopoiesis Group Drug Discovery in the Manchester 12 Cancer Research Centre Akira Orimo 42 Stromal-Tumour Interaction Group Research Groups – Paterson Institute Research Groups – The University of Manchester School of Cancer and Enabling Sciences Crispin Miller 16 Applied Computational Biology and Bioinformatics Group Robert E Hawkins and Peter L Stern 46 Biological, Immune and Gene Therapy Group Geoff Margison 18 Carcinogenesis Group Vaskar Saha 48 Children’s Cancer Group Karim Labib 20 Cell Cycle Group Tim Illidge 50 Targeted Therapy Group Iain Hagan 22 Cell Division Group Catharine M.L. West 52 Translational Radiobiology Group Nic Jones 24 Cell Regulation Group Robert Hawkins 54 Medical Oncology: Cell Therapy Group Angeliki Malliri 26 Cell Signalling Group Gordon Jayson 56 Medical Oncology: Translational Caroline Dive and Malcolm Ranson 28 Anti-Angiogenesis Group Clinical and Experimental Pharmacology Group Ivan Ahel 30 DNA Damage Response Group Research Services 58 Peter L Stern 32 Research Publications 66 Immunology Group Nullin Divecha 34 Seminar Series 2009 74 Inositide Laboratory Tim Somervaille 36 Postgraduate Education 76 Leukaemia Biology Group Operations 78 Cancer Research UK’s 84 Local Engagement and Development Acknowledgement for Funding 86 of the Paterson Institute Career Opportunities at the 87 Paterson Institute Contact Details 88 4 | Paterson Institute for Cancer Research Scientific Report 2009 Director’s introduction Welcome to the 2009 Paterson Institute Annual Scientific Report. It has been a particularly important year with the completion of the Institute’s Quinquennial Review but also with the initiation of the new Drug Discovery Centre. Nic Jones The Institute is very privileged to receive such expectations and thereby justifies the long-term strong financial core support from Cancer commitment they make to the Institute and to Research UK. In return the Institute has to the Institute Director. For us, it is a strong ensure that it is undertaking research of the reminder of the competitive environment we highest international quality and that the work in and the duty we have to deliver high- research that we do will impact significantly quality and relevant research. towards achievement of CR-UK’s major research goals as outlined in their 5-year strategic plan. The review took place at the end of June with a There are a number of ways of measuring our very successful outcome. The review party success which includes periodic review of all the praised the continuing progress we had made research programmes. However, perhaps the over the last five years and were especially most important process is the Quinquennial supportive of the establishment of the Institute Review which is commissioned by CR- Manchester Cancer Research Centre (MCRC), UK and involves assembling a team of world- the progress it had made in such a short-period leading scientists experienced in running of time since it was initiated and the significant research organisations or institutes. The review role the Institute plays in delivering the MCRC’s team visits the Institute over a two-day period goals and ambitions. I was obviously very and assesses in depth the Institute’s performance pleased that the Institute received such strong over the last five years and also reviews the support and that developments over the last few strategic direction and plans for the next five- years were positively recognised. However, year period. For CR-UK, such reviews are these reviews are not just about judgement of essential for them to ensure that the ‘return on past activities but are also about assessing and investment’ is meeting or exceeding their advising on future directions and in this respect Director’s Introduction | 5 the review was also supportive and provided research efforts and instil within the Institute a valuable, constructive input into the drug hunting culture. Donald Ogilvie joined us development of future programmes which will in February 2009 to lead this new development. ensure that we can build on the progress we He previously acquired considerable experience have made over the next five years. Cancer in leading drug discovery programmes at research is at a very exciting stage and driven by AstraZeneca having overseen the development new technologies, new and exciting avenues are of at least eight candidates from target opening up especially at the laboratory/clinical identification to clinical trials. A chemistry lead interface. Given our proximity to The Christie (Allan Jordan) has also been recruited as well as NHS Foundation Trust and our involvement in a number of chemistry and biology team the MCRC, we are well placed to take advantage members and refurbishment of laboratory of these new opportunities. facilities suitable for this type of activity has just been completed. Thus in 2010 a number of An exciting development that really began to discovery programmes will be initiated and we take off this last year is the Drug Discovery look forward to experiencing the success of the Centre, an initiative that is a key component of Centre over the years to come. CR-UK’s strategic plan to increase its capability and activity in the development of small Recruitment and retention of internationally molecule drugs. Two new centres are being competitive scientific leaders is essential for developed linked to the Paterson Institute and maintaining research excellence and building our sister institute in Glasgow, the Beatson areas of research strength. Many of our recruits Institute. CR-UK is providing significant new are at the Junior Group Leader level and after funding in order to develop the centre at the six years they undergo a rigorous evaluation to Paterson Institute. Linking the centre to the consider promotion to Senior Group Leader Institute has a number of advantages including level and as a consequence long-term and the potential interactions with already existing increased commitment to research support. This groups involved in biomarker research and the is a very important quality-control step and the testing of new therapies in early clinical trials, the opinions of outside experts in the field are exploitation of the cancer biology research crucial to the decision that is made. Only those ongoing with the Institute and the wider leaders who have a demonstrable international interactions facilitated through the MCRC. There profile and have contributed significantly to the are real opportunities for academic drug field are expected to be successful. During the discovery programmes to exploit and add value last year, two group leaders were evaluated for to the research that we do and to consider such promotion – Georges Lacaud and Valerie areas of real clinical need that for a variety of Kouskoff. We are delighted that both were reasons might not be attractive to the successful and will continue their careers and pharmaceutical industry. Developing new drugs productive research programmes in the Institute. is very challenging and takes many years but the They both work on the differentiation of benefits to us of having such a Centre within the embryonic stem cells especially down the Institute will be tangible from the start – it will haematopoietic lineage. Understanding in detail greatly enhance the multidisciplinary how this process is regulated is important to environment of the Institute, provide understanding a number of haematological leading–edge chemical tools to enhance our malignancies. Another indicator of research 6 | Paterson Institute for Cancer Research Scientific Report 2009 success and reputation is winning individual Inevitably the MCRC was an important theme awards and this year two of our group leaders considered by the Institute review party and received an award. Iain Hagan was elected as an there was great enthusiasm for the partnership EMBO member. Membership is a lifelong and in particular the potential that is has for honour with new members nominated and promoting translational research and ensuring elected annually based on proven excellence in that research funding can ultimately benefit research. Karim Labib was awarded the Hooke cancer patients. Much progress within the Medal by the British Society for Cell Biology. The MCRC has been made over the last year: medal is awarded to an emerging leader in cell investment in breast cancer research continued biology and will be presented to Karim at the with the appointment to the University Medical annual spring meeting in 2010. School of Professor Jonas
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