UNIVERSITY OF NOTTINGHAM RECRUITMENT ROLE PROFILE FORM

Job Title: Research Associate/Research Fellow in Translational Stem Cell Technology & Bioengineering

School/Department: The School of Medicine, Division of Cancer & Stem Cells

Salary: £25,513 - £37,394 per annum, depending on skills and experience (£28,695 minimum with a PhD). Salary progression beyond this scale is subject to performance

Job Family and Level: Research & Teaching Level 4CTG/4

Contract Status: This full time post will be offered on a fixed-term contract for 3 years, with anticipated start date of 1 Jan 2016.

Hours of Work: Full time

Location: University Park

Reporting to: Associate Professor in Stem Cell Glycobiology

The Purpose of the New Role: This post will recruit a talented, proactive postdoctoral researcher to work on an exciting interdisciplinary, translational project funded by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). The project will combine cancer cell biology, matrix biology, glycobiology, proteomics and biomaterials science to address a workplan entitled: “A multi-cellular 3D model of human breast tissue to replace rodent xenograft models in breast cancer research”. This post will be based in Nottingham but will collaborate extensively within the collaborative group, which includes Dr Gillian Farnie and Professor Tony Howell from the Institute of Cancer Sciences and the Christie Hospital in Manchester. This project will develop a bespoke non-animal based in vitro system that better replicates the tissue specific environment experienced by human breast and breast cancer cells, creating model systems that are then suitable for use in diagnostics and drug screening as well as improving our understanding of the interactions of breast cancer cells with their local environment. We intend to focus initial development of this breast tissue model on the pre-invasive breast cancer, ductal carcinoma in situ (DCIS), characterised by proliferation of malignant epithelial cells to fill the breast duct but separated from the stroma by an intact basement membrane and a layer of myoepithelial cells. If left untreated, progression to invasive cancer is observed in 30-50% of patients creating a clinical challenge to identify which patients do not require further treatment. Therefore, DCIS can be viewed as a temporary hiatus in malignant development, offering an opportunity for researchers to determine the key factors in the cellular microenvironment permitting invasive progression and providing an ideal test environment for our 3D model to be built upon. The successful candidate will combine excellence in research, collaboration, communication and meeting deadlines with knowledge of one or more of these areas, including: experience of using hydrogels or other 3D cell culture environments and / or cancer cell biology; glycobiology

1 (specifically glycosaminoglycans) and proteomics, particularly of matrix proteins; multicellular culture systems / cell characterisation including molecular biology skills and high quality imaging.

Main Responsibilities % time 1. Work collaboratively within a team at the University of Nottingham (includes 70% ~20 researchers and PhD students), and with academic/clinical partners in Manchester and Boston (USA). This work will contribute to the goal of producing a hydrogel-based mimetic of the human breast which can be functionalised to reflect differences in matrix composition and structure. The post holder will be required to travel to Manchester to learn skills, transfer technologies and carry out essential practical components of the project. This will include staying in Manchester for up to 5 consecutive days at a time in the first year of the project. 2. Prepare data, reports and presentations for project meetings held between the 10% partners in Nottingham and Manchester. The candidate will excel at achieving milestones / deadlines, which will be continuously evaluated and reported to the funder annually. 3. The post holder will be required to travel to groups in the UK and USA who are 10% trialling the hydrogel technology to learn skills and transfer technologies. 4. Contribute to day to day development and running of the Merry Group, and to 10% undertake manuscript preparation and conference presentations 5. You are expected to make a contribution to teaching that is in balance with wider contributions to research and other activities.

Knowledge, Skills, Qualifications & Experience Essential Desirable Qualifications/ Nearing completion of a PhD or Education holding a PhD in Biological Sciences, Cancer Studies or Engineering equivalent Skills/Training Expertise in working with breast A proven ability to prepare and cancer tissue and cell culture publish in excellent journals, and work proactively and productively in Expertise in working with complex one or more of the areas below: equipment, such as robotic 1. Human primary and platforms, confocal plate readers. cell-line culture; Proven ability to teach, e.g. to 2. Hydrogel or other 3D PhD or Masters levels students cell culture experience; 3. Cell characterisation Evidence of excellence within the including viability, field, such as awards and prizes proliferation and metabolic assays; Knowledge of 3D modelling of tumours 4. Experience of proteomic analysis and data handling, particularly relating to the extracellular matrix; 5. Skills in immunocytochemistry and 3D imaging including confocal

2 microscopy and real-time imaging; 6. Cell and tissue bioengineering; familiarity with biomaterials, particularly hydrogels, 7. Experience of glycan analysis using biochemical, mass spectrometric or immunocytochemical means

Evidence of combining excellence in research, collaboration, communication and meeting deadlines

Ability for independent and flexible thinking.

Ability to present to scientific and lay audiences Other Willingness to adopt the Ethos and Principles of the School of Medicine to improve the student experience.

Scope of the Role To undertake research and day-day management of a research project that requires a high degree of competence in one or more of the research areas listed above. An aptitude for critical thinking and a flexible approach to collaborative research is critical, since the project will interact with multiple centres. The successful candidate will be frequently required to work seven days a week to maintain challenging cell cultures and this will play a major role in ensuring the success of the project. They will also be expected to make a significant contribution to the Stem Cell Biology Group via management, training and co-ordination of specific initiatives. If they wish, they will also be able to contribute to occasional teaching to the MSc Stem Cell Technology.

Additional Information

Project Overview: A synopsis from the funder can be found at: https://www.nc3rs.org.uk/multi-cellular-3d-model-human-breast-tissue-replace- rodent-xenograft-models-breast-cancer-research

Abstract: We aim to reduce the number of rodent models investigating the biology of the breast by developing a superior in vitro matrix incorporating bespoke human breast extracellular matrix (ECM) components, providing a robust culture model as the go-to platform for exploring the biology of the breast and breast cancer. Drs Merry and Meade have developed a simple peptide hydrogel system originally optimised for the culture of stem cells. In collaboration with Dr Farnie and Prof Howell, who provide expertise in primary breast cell culture, ductal carcinoma (DCIS) and breast ECM/density, we have pilot data demonstrating that the hydrogel is suitable for the growth of typical in vitro 3D normal and DCIS breast structures. As with the vast majority of cancers, the interaction of DCIS cells with their local microenvironment, the surrounding stroma and ECM, is fundamental in defining their proliferation, transformation to malignancy and invasion. Our hydrogel is well positioned to replicate aspects of the complex mixture of proteins

3 and glycans that embeds and supports cells, and can also be manipulated to mimic ECM stiffness (breast density) which is a key predictor of DCIS recurrence and primary invasive breast cancer development. We will use a combination of proteomics and glycomics to identify the key ECM components defining dense and non-dense breast tissue in normal, DCIS and invasive breast cancer conditions. The proteins and glycans will then be combined to generate a panel of 6 bespoke hydrogel environments modelling the range of tissue types. We will validate the model using multicellular 3D culture and assay for ECM remodelling by encapsulated cells, directly assessing the ability of our in vitro model system to replicate human breast tissue. Finally, we will incorporate immune cells into the gels, thereby addressing a key feature of animal models that currently separates them from in vitro systems.

The Postdoctoral Research Assistant post advertised here will be based in Nottingham’s Wolfson Centre for Stem Cells, Tissue Engineering and Modelling (STEM), which houses a purpose-built stem cell culture suite and state of the art facilities. STEM promotes a multidisciplinary research ethos, where biologists, mathematicians and tissue engineers regularly integrate in a creative and internationally-competitive research environment. The postholder will be encouraged to enrol in appropriate management and personal development training programmes run through the University’s Staff and Educational Development Unit.

Additional facilities at the University of Manchester include advanced imaging and proteomic core facilities based at the CRUK Manchester Institute site. The Postdoctoral Research Assistant will utilise the gated Stimulated Emission Depletion (gSTED) microscope which allows greater resolution and clarity for complex 3D models. The imaging facility is also the first the UK to have access to the PerkinElmer Opera Phenix, a modified spinning disk confocal High Content Screening system, which will allow rapid data throughput with quantitative analysis capabilities. Our proteomics team have over fifty years of analytical experience and have a track record of collaborative project support to simultaneously enhance research output and novel workflows designed to answer previously intractable biological questions.

Informal enquiries should be directed to [email protected] but applications must be made through the online system.

4 Appendix 1

The University of Nottingham The University of Nottingham is a global-leading, research-intensive university with campuses in the UK, Malaysia and China. Our reputation for world-class research has yielded major scientific breakthroughs such as Nobel-winning MRI techniques, drug discovery, food technologies and engineering solutions for future economic, social and cultural progress.

Already ranked among the UK’s elite universities and global polls for research excellence, our reputation for world-class research has been further enhanced with the 2014 results of the Research Excellence Framework (REF). In addition to scoring highly in quality rankings covering major disciplines in science, engineering, the social sciences, medicine, business and the arts, it is Nottingham’s research power rankings which demonstrate the impressive volume of excellent research which is carried out. We are now ranked 8th in the UK on a measure of ‘research power’ which takes into account both the quality of research and the number of research-active staff who made REF returns, confirming Nottingham’s place in the top tier of the world’s elite higher education institutions.

The main University campus is set beside a lake, in an extensive belt of woodland, parks and playing fields. The 330 acre University Park Campus is the focus of life for more than 32,000 students and houses the majority of the University’s academic schools and many of the central Services. The Jubilee campus is situated 2 miles away from the University Park, and provides extra capacity. The University Medical School is situated next to the University Park. Together with the University Hospital, it forms the Queen’s Medical Centre (QMC). University of Nottingham Medical School Nottingham has a strong reputation for both clinical medicine and teaching. As one of the most popular medical schools in the country, it is able to select excellent students and produce and attract good junior doctors. The School of Medicine comprises the Divisions of Cancer and Stem Cell Sciences, Child Health, Obstetrics and Gynaecology; Clinical Neuroscience; Epidemiology and Public Health; Primary Care; Psychiatry and Applied Psychology; Rehabilitation and Ageing; Medical Sciences and Graduate Entry Medicine; Respiratory Medicine; Rheumatology, Orthopaedics and Dermatology and the Nottingham Digestive Diseases Centre. The School also hosts the School of Medicine Education Centre, the Centre for Interprofessional Education and Learning, the Clinical Research Facility, the Clinical Skills Centre, NIHR design Service East Midlands, Nottingham Clinical Trials Unit, PRIMIS and Medical Imaging Unit. The School of Medicine brings together in one School staff undertaking research for the benefit of the health of patients. It includes all primary care and hospital-based medical and surgical disciplines, principally in the Queen’s Medical Centre and City Hospital Nottingham Campuses, Royal Derby Hospitals NHS Foundation Trust and also at the University’s main campus and at the King’s Meadow and Jubilee Campuses. Most of our School’s Senior Researchers and Teachers are also clinicians who dedicate 50% of their time to patient care within the Nottingham University Hospitals NHS Trust & Royal Derby Hospitals NHS Trust. This close juxtaposition brings cutting- edge clinical care to our patients and clinical relevance to our research and teaching. We are closely integrated with our full time NHS clinical colleagues, many of whom are themselves leaders in research and teaching and who work closely with the University and this increases the mutual benefit from integration between the University and NHS.

5 Mission: Our mission is to improve human health and quality of life locally, nationally and internationally through outstanding education, research and patient care.

Priorities: 1. Teaching and learning, particularly training tomorrow’s doctors and teaching specialised postgraduates 2. Research and research training: We will perform and support the highest quality “big” research which impacts on human health and disease 3. Partnership with the NHS and other healthcare providers 4. Visibility and profile of the School of Medicine: We will do what we do better, and we will tell others about it

Ethos and principles: 1. Having people and patients at the heart of all we do: our teaching and learning, our research and our patient care 2. Contribution within the School of Medicine and to society beyond our immediate roles; helpfulness and service 3. Openness and fairness, with particular emphasis on communication (both internal and external) and on equality and diversity among students and staff 4. Personal and group responsibility for all aspects of our work, within a culture of opportunity and reward Our research spans 11 major themes, ranging from cancer to vascular medicine. We work closely with industry and the NHS. Our world-leading research ranges from basic and translational science through to clinical trials, epidemiology, and health services research. Our clear theme is improving human health, underpinning a vibrant postgraduate research training programme leading to PhD or DM. Many of our academics are clinicians, using their expertise to provide cutting edge specialised treatment to NHS patients; reflecting our ethos that patients are at the heart of all we do. In the 2014 Research Excellence Framework the four Units of Assessment included in the School of Medicine were among the six most improved in the whole University since RAE 2008: 82% of our research in 2014 was graded as world-leading or internationally excellent. Our research spans 11 major themes and ranges from basic and translational science through to clinical trials, epidemiology, and health services research. We work closely with industry and the NHS. Our research is underpinned by a strong postgraduate research training programme leading to PhD or DM. Our major research themes are in Cancer and Stem Cells; Child Health, Obstetrics & Gynaecology; Clinical Neurosciences; Dermatology; Digestive Diseases; Epidemiology and Public Health; Mental Health; Musculoskeletal physiology and disease; Primary Care; Rehabilitation and Ageing; Respiratory Medicine; and Renal Medicine The School of Medicine trains tomorrow’s doctors on a vibrant undergraduate medical course with a unique intercalated BMedSci, as well in a specialised graduate-entry programme built around clinical problem solving. We teach medicine and related disciplines at both undergraduate and postgraduate level. We have a dedicated clinical academic training programme and are committed to training PhD and doctoral research students and to supporting postdoctoral clinicians and scientists in their research. The School of Medicine holds a Bronze Athena SWAN award in recognition of our commitment to advance the representation of women in science, technology, engineering, medicine and mathematics (STEMM). The award reflects our commitment to promoting equality and diversity. Please see http://www.nottingham.ac.uk/medicine/about/athena-swan.aspx. Professor Tony Avery is Dean of the School of Medicine. For further information, please see our website http://www.nottingham.ac.uk/medicine

6 Academics The Department of Stem Cells, Tissue Engineering and Modelling (STEM) comprises a team of successful, young scientists with an interest in combining a range of state-of-the-art technologies to further key basic questions and biomedical goals utilizing stem cell systems. The academics comprise the Stem Cell Biology Group, Tissue Engineering Group and the Mathematical Modelling Group. STEM academics are highly research active and have a current grant holding in excess of £10m. Academics within STEM were instrumental in winning a £6.5m Doctoral Training Centre Award held between Nottingham, Loughborough and Keele Universities, which is in the final stages of training 50 PhD students over the a 5 year period (2009-2014). This award has been renewed for another 5 year period from 2015-2020. The same University partners have also received funding for a £6.3m EPSRC Centre in Regenerative Medicine.

The Stem Cell Biology group is within the Division of Cancer & Stem Cells and forms part of the School of Medicine (www.nottingham.ac.uk/medicine/research/themes/cancer-and-stem- cells/index.aspx). Professor Chris Denning is applying his expertise in genetic modification and gene targeting to human embryonic / induced pluripotent stem cells, particularly to establish novel human disease models / methods for translational approaches such as drug development. He is a partner in the £2.5m British Heart Foundation Centre for Regenerative Medicine that is held jointly with Imperial College London. Dr Virginie Sottile investigates the in vitro differentiation properties of both neural and mesenchymal stem cells, as well as their differentiation in situ upon transplantation into the chick embryo. Dr. Alexey Ruzov investigates how epigenetic modifications such as 5-hydroxymethyl-cytosine regulate cell fate and development. During 2014-16, a two-phase recruitment process will add 4 staff from Lecturer to Professor level to this department. New academic appointees to the department will include Dr. Nick Hannan (from University of Cambridge; started 1st July 2015) to lead a programme on hPSC differentiation in lung and gut lineages. Dr. Cathy Merry (from University of Manchester; started 1st Sept 2015) will bring her programme on Glucosaminoglycans (GAGs). During 2015/16 we will recruit a further Associate Professor and a Full Professor to the growing department.

Included within the Tissue Engineering Group are Professor Kevin Shakesheff, who combines the incorporation of biomolecules into novel scaffold materials for regeneration of tissues such as liver and bone (www.nottingham.ac.uk/pharmacy/research/ddte/index.aspx). Kevin is also pioneering the use of supercritical fluids to enhance cell survival on synthetic polymers. He is lead in the £3.5m MRC Regenerative Medicine Hub for Accelular Technologies. Dr Felicity Rose focuses on the tissue engineering of intestinal, bone and cartilage tissue using a variety of scaffolds and bioreactor systems and is also engineering wound repair systems for corneal transplants. Dr Lee Buttery is investigating the engineering of scaffolds to improve both 3D differentiation and clinical delivery of both fetal osteoblasts and osteogenic progenitors derived from embryonic stem cells.

The application of mathematical modelling to regenerative medicine systems is a major interest of Profs John King, Marcus Owen and Simon Preston. Collectively, their interests within Centre for Mathematical Medicine & Biology (http://www.nottingham.ac.uk/cmmb/index.aspx) include development and validation of mathematical models for tissue growth, cell signalling and differentiation.

Facilities Housed within the purpose-built laboratories and offices of the Centre for Biomolecular Sciences building, STEM is directly linked to the University Medical School, Fertility Clinic and Clinical Grade Stem Cell & Tissue Processing Laboratory. STEM scientists also have a close proximity with physical scientists, including electrical / optical / manufacturing engineers, polymer biologists, chemists, physicists etc.

STEM has fully equipped molecular biology laboratories that are complimented by dedicated facilities for radioisotope studies, for chick embryo incubation, for bacterial culture, for tissue dissection/ preparation, for PCR set-up and in situ hybridization, for histology/

7 immunocytochemistry and for cell imaging. In addition, the culture suite is one of the best in an academic institution within the UK if not Europe and has 21 class II culture hoods dedicated to human stem cell culture, imaging and manipulation. Our most recent acquisitions of a bespoke £1m stem cell culture & differentiation robot, automated Patchliner electrophysiology, CardioXcyte impedance system and an Operetta high content confocal plate imager. These have been acquired through grants including a £1.3m BBSRC industrial partnership award with Syngenta, a £2.3m EPSRC award and a £715K MRC award. The tissue engineering laboratories include a supercritical fluid laboratory and state of the art facilities for scaffold bioengineering. Complimentary computing facilities and IT support are available, with dedicated computing laboratories for our mathematical modellers.

Between the 3 major University hospital sites, the Medical School offers a full range of clinical departments and clinical academics. Elsewhere in the University, a new Veterinary School at the Sutton Bonington campus provides additional opportunities for collaboration.

Teaching In 2007, STEM started the world’s first taught Masters Course in Stem Cell Technology. This course has a capacity for 16 students each year, who typically comprise 6 from the UK and 10 internationals. It has attracted funding from BBSRC for 12 Scholarships (2007-2010) and 12 from MRC (2009-2012). The course comprises 6 Modules, which include 1, Cell & Developmental Molecular Biology; 2, Pluripotent Stem Cells; 3, Adult Stem Cells; 4, Translation Technologies for Stem Cells; 5, Transferrable Skills; 6, a 3 month Summer Research Project. More details can be found at http://www.nottingham.ac.uk/pgstudy/courses/medicine/medical-sciences/stem-cell- technology-msc.aspx.

Appendix 2

Nottingham Central within the East Midlands, Nottingham is a vibrant and prosperous city with something to offer everyone. It is one of the UK’s leading retail centres and has a huge variety of restaurants, bars and nightclubs which attract people from all over the UK. Culturally, it has good theatres, an arena which attracts both national and international performers and a range of historical interests relating to subjects such as the lace industry, Lord Byron and DH Lawrence. Nottingham is also known for sport, being the home of Trent Bridge Cricket Ground, Nottingham Forest and Notts County Football Clubs, the National Water Sports Centre and the Nottingham Tennis Centre. There is a good network of roads with easy access to the M1 and the A1, a fast frequent rail service to London and other major cities. Nottingham East Midlands Airport is only eighteen miles away. The city is set within a county of outstanding natural beauty which includes Sherwood Forest, Wollaton Park, lively market towns and wonderful historic buildings. Housing is relatively inexpensive and, in addition to the two Universities, there are excellent schools and colleges available. To find out more about Nottingham, use the following links: Nottingham County Council – Tourism http://www.experiencenottinghamshire.com/ University of Nottingham http://www.nottingham.ac.uk Zoopla (Guide to local properties) http://www.zoopla.co.uk/

My Nottingham (information on schools, term dates, school transport etc.) http://www.nottinghamcity.gov.uk/index.aspx?articleid=8524

8 The University of Manchester The University of Manchester is Britain’s largest and most popular university, with a distinguished history of academic achievement and an ambitious agenda for the future. The University, with income in excess of £780 million, has four Nobel Prize winners amongst its current academic staff, and has embarked on an exciting and bold course which aims to make us one of the top 25 universities in the world, as set out in the University’s strategic vision for 2020: http://www.manchester.ac.uk/2020 The University became the largest single site University in the UK in 2004 with the merger of the Victoria University of Manchester and the University of Manchester Institute of Science and Technology (UMIST).

The core commitment of our research strategy is to perform research of the highest quality and to continue to raise the level and ambition of our world class and world leading standards of excellence. As part of our strategy and vision for the University, we are working to build a 21st century campus with cutting-edge research accommodation and facilities. In the last few years we have spent more than £400m on transforming our campus and building a world-class environment for outstanding scholars, teachers and internationally acclaimed research teams. This is the largest investment ever seen in UK higher education history. A further £250m investment by 2015 will bring the total spend to more than £650m.

In REF 2014, 83% of research activity at The University of Manchester was judged to be “worldleading” (4*, 35%) or “internationally excellent” (3*), confirming the University’s place as one of the UK’s top research universities – in fifth place in terms of research power.

The Institute of Cancer Sciences The Institute of Cancers Sciences is one of six Faculty Institutes within the Faculty of Medical and Human Sciences http://www.mhs.manchester.ac.uk/. It is made up of five research themed Centres: Haematological Oncology; Paediatric, Teenage and Young Adult Cancer; Personalised Therapy; Radiation; and Women’s Cancer. It is based on the same site as the Cancer Research UK Manchester Institute and The Christie Hospital, which provides a focus for cancer research activity that combines an international reputation for cancer research with the largest scale cancer clinical service in the UK.

Other activity in the Institute is based either on the University’s Oxford Road site or in key Manchester Academic Health Science Centre (MAHSC) partner sites at Central Manchester University Hospitals NHS Foundation Trust, University Hospital of South Manchester NHS Foundation Trust and Salford Royal NHS Foundation Trust. The large patient base found in Greater Manchester and linked to the research network provides major opportunities for the growth of clinical and translational research, a key objective of the Trusts and the University. The new Faculty Institute will play a key role in taking advantage of this opportunity to seamlessly link basic and clinical science http://www.cancer.manchester.ac.uk/research/.

Academics Dr Farnie and Professor Howell are part of the Institute of Cancer Sciences (ICS) and are based at laboratories within the CRUK Manchester Institute and the new Manchester Cancer Research Centre (MCRC). They have access to all of the CRUK core facilities including, Advanced imaging and Flow cytometry, Biological Mass spectrometry, Histology and the Molecular Biology Core Facility http://www.cruk.manchester.ac.uk/Home. They are part of a highly translational research environment within ICS and are members of the Manchester Breast Centre which integrates 20 clinical and academics principal investigators working in breast research throughout the University This has forged strong collaborations which have enabled our research to have clinical impact. http://www.breastcentre.manchester.ac.uk/

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