SCIENTIFIC REPORT 2017 cruk.org SCIENTIFIC COVER IMAGE Mitochondria, the powerhouses of the cell, are required for cancer cell death. This image shows mitochondrial shape REPORT changes during cancer cell death, where each colour represents mitochondrial shape at a specific time point during cell death. Image supplied by Joel Riley, a post-doc in Stephen Tait’s group. 2017 BEATSON INSTITUTE CONTENTS SECTION 1 Shehab Ismail 52 DIRECTOR'S INTRODUCTION 04 Structural Biology of Cilia INSTITUTE OF CANCER SCIENCES 06 Laura Machesky 54 INTRODUCTION Migration, Invasion and Metastasis RESEARCH HIGHLIGHTS 08 Jim Norman 56 GABRIELA KALNA OBITUARY 11 Integrin Cell Biology TESSA HOLYOAKE OBITUARY 12 Michael Olson 58 BACKGROUND 13 Molecular Cell Biology Owen Sansom 60 CANCER RESEARCH UK BEATSON INSTITUTE Colorectal Cancer and Wnt Signalling Sara Zanivan 62 CANCER GROWTH AND METABOLISM Tumour Microenvironment and Proteomics Imran Ahmad 16 Models of Advanced Prostate Cancer DRUG DISCOVERY Peter D. Adams 18 Justin Bower & Heather McKinnon 66 Epigenetics of Cancer and Ageing Drug Discovery Unit Eyal Gottlieb 20 Tumour Metabolism ADVANCED TECHNOLOGIES Danny Huang 22 Leo Carlin 70 Ubiquitin Signalling Beatson Advanced Imaging Resource (BAIR) Jurre Kamphorst 24 Bioinformatics and Computational Biology 72 Cancer Metabolomics Sara Zanivan 73 Hing Leung 26 Proteomics Prostate Cancer Biology Emma Shanks 74 David Lewis 28 Functional Screening Molecular Imaging Gillian Mackay 76 Daniel J. Murphy 30 Metabolomics Oncogene-Induced Vulnerabilities Jennifer Morton 78 Kevin Ryan 32 Preclinical Precision Pancreas Tumour Cell Death Karen Blyth 80 Stephen Tait 34 Transgenic Models of Cancer Mitochondria and Cell Death Douglas Strathdee 82 Saverio Tardito 36 Transgenic Technology Oncometabolism David Lewis 84 Alexei Vazquez 38 Translational Molecular Imaging Mathematical Models of Metabolism SECTION 3 CANCER METASTASIS AND RECURRENCE Cancer Research UK Beatson Institute building RESEARCH FACILITIES 88 Tom Bird 42 PUBLICATIONS 92 Liver Disease and Regeneration CONFERENCES AND WORKSHOPS 112 David Bryant 44 SEMINARS 114 Molecular Control of Epithelial Polarity STUDENTSHIPS AND POSTDOCTORAL 116 Leo Carlin 46 FELLOWSHIPS Leukocyte Dynamics OPERATIONAL SERVICES 118 Seth Coffelt 48 THANKS FOR SUPPORTING US 120 Immune Cells and Metastasis PATRONS AND BOARD OF DIRECTORS 122 CONTACT DETAILS 123 Robert Insall 50 Cell Migration and Chemotaxis 2 SCIENTIFIC REPORT 2017 CANCER RESEARCH UK BEATSON INSTITUTE 3 DIRECTOR’S INTRODUCTION Researchers Drs Saadia Karim and David Vincent receive recognition for their research engagement activities In August of this year, Professor Owen Sansom was appointed as the next Director of the Cancer Research UK Beatson Institute. As its newest Director, Owen here sets out his vision for the Institute's strategy over the next five to ten years, along with some of the research highlights there were during 2017. Vision and strategy including for a number of senior clinicians in the Director of the Cancer Research Over the past ten years, the Beatson Institute has areas of particular clinical interest in Glasgow, UK Beatson Institute built an excellent reputation for basic cancer such as colorectal cancer and hepatocellular research, including world-class metabolism carcinoma. Professor studies and renowned in vivo modelling of Owen Sansom tumour growth and metastasis. This is Highlights FRSE, FMedSci something that current and former members of This has been our most successful year in the Institute can be very proud of. My goal for winning external grant funding and finding ways and now heads up both her research group and Martin Drysdale resigned as Director of the Drug the future is for this discovery work to continue to expand our research base, including the Proteomics team. We also held a number of Discovery Unit (DDU) in July to take up a apace but for it to also be applied to preclinical functional imaging, precision medicine and advisory mid-term reviews, for junior group prestigious role at the Broad Institute in the US, and clinical studies. This will include working informatics. leaders Dr Alexei Vazquez and Dr David Bryant and in the interim period our respective heads of with the well-established clinical pipeline in and for clinician scientist Dr Tom Bird. We are very chemistry and biology, Justin Bower and Heather Glasgow, exemplified by initiatives such as Two large initiatives, which researchers at the grateful to all of the external reviewers who McKinnon, have been acting as DDU leads. They PRECISION-Panc, which began this year. To do Institute are participating in, began this year. The participated in these important meetings. have recently been appointed as joint heads of this, we will work closely with colleagues in the Grand Challenge team (led by Josephine Bunch, the DDU, and we will work with them very closely wider Glasgow Cancer Centre, particularly National Physics Laboratory) is focusing on I was pleased by the progress of some of our in the coming years to develop exciting new clinical academics and clinicians focused on using state-of-the-art mass spectrometry intermediate clinicians this year - Colin Steele (a targets for cancer treatment. Mike Olson will also the treatment of cancer patients. imaging to map metabolism in vivo, something former clinical research fellow in my group) was be leaving the Institute in April 2018 to lead a that aligns very closely with previous work at the awarded an NHS Education Scotland/CSO department in Ryerson University (Toronto), As a core-funded Institute, I believe we also Institute. Meanwhile, PRECISION-Panc (led by Postdoctoral Clinical Lectureship, while Nigel bringing cancer and physical sciences together need to continue to do high-risk/high-gain Andrew Biankin, Owen Sansom and Jeff Evans) Jamieson won a CRUK Intermediate Clinical after winning a highly competitive Canada projects, and an important component of this aims to utilise functional stratified medicine Fellowship. I was also delighted to be elected a Research Chair. will be the advanced technologies established approaches to deliver new treatment options for Fellow of the Academy of Medical Sciences. In both within the Institute and the University of pancreatic cancer. Much of the preclinical work addition, two of our researchers, Drs Saadia In memory Glasgow, which underpin much of what we do. will be done within the Institute, in particular by Karim and David Vincent, were recognised with The year ended on an incredibly sad note with Our research themes will remain broadly the Dr Jennifer Morton, who now leads the CRUK Flame of Hope Special Commendations the loss of two of our most outstanding and same (cancer growth and metabolism, and Preclinical Precision Pancreas Laboratory. for all of their research engagement activities unique contributors to cancer research in cancer metastasis and recurrence) but with a over the years, while Dr Emma Shanks was Glasgow - Professor Tessa Holyoake and Dr re-emphasis on: In addition, Pancreatic Cancer UK awarded us a awarded CRUK's Communications and Brand Gabriela Kalna. The very warm tributes paid to Future Leaders Academy, enabling us to appoint Ambassador Prize as an inspiring communicator them in this report (pages 11 and 12) demonstrate • Cancer vulnerabilities caused by their four PhD students, along with a fifth funded by of its research. how well regarded they were and how much aberrant metabolism; Pancreatic Cancer Scotland, to our graduate they will be missed as both friends and • Interplay between the tumour studentship programme, which this October Arrivals and departures colleagues. microenvironment, metastasis and saw its largest intake to date (23 students in In January, Dr David Lewis joined us from the recurrence; total). CRUK Cambridge Institute to establish preclinical • Biology of early disease, aimed at developing functional imaging at the Institute. In support of a ‘precision prevention’ approach. We continue to monitor the progress of our this, the Beatson Cancer Charity has provided research groups. Professors Robert Insall and generous funding (via the Glasgow Cancer Our aim will be to identify non-clinical and Laura Machesky's quinquennial reviews, held in Centre) that will allow the establishment of a clinical leads for each of our themes, and for May, were very positive, while Dr Sara Zanivan facility at Gartnavel for probe synthesis. This there to be a programme of recruitment, was promoted to Senior Staff Scientist in March includes the appointment of a senior chemist and a physicist to support the group. 4 SCIENTIFIC REPORT 2017 CANCER RESEARCH UK BEATSON INSTITUTE DIRECTOR’S INTRODUCTION 5 www.gla.ac.uk/researchinstitutes/cancersciences INSTITUTE OF CANCER SCIENCES INTRODUCTION This year, there were a number of highlights within the Institute of Cancer Sciences (ICS), University of Glasgow in line with its primary goal of delivering cutting-edge translational cancer research for patient benefit. Director of the Institute We saw the start of PRECISION-Panc, a dynamic Panc clinical development platform (Leads: Jeff of Cancer Sciences and coordinated research platform to define, Evans and Juan Valle, Manchester). The ultimate understand, test and implement stratified aim is to develop a multi-drug, multi-sub-study, Jeff Evans therapeutic strategies for pancreatic cancer biomarker-driven family of clinical trials that use FRCP Edin (PDAC). The initiative is centred on discovery state-of-the-art genomic profiling to match and preclinical and