RECRUITMENT ROLE PROFILE FORM
Job Title: Research Associate/ Research Fellow in Translational Stem Cell Technology & Automation
School/Department: School of Medicine, Division of Cancer and Stem Cells
Salary: £25,513 - £32,277 per annum, depending on skills and experience. Minimum salary with relevant PhD £28,695 per annum
Job Family and Level: Research & Teaching Career Training Grade Level 4/ Level 4
Contract Status: This full time post will be offered on a fixed-term contract until 29 April 2017.
Hours of Work: Full time, 36.25 hours per week
Location: Centre for Biomolecular Sciences, University Park
Reporting to: Professor of Stem Cell Biology
The Purpose of the New Role:
The Research Associate/ Research Fellow in Translational Stem Cell Technology & Automation will work on an exciting £1.2 million interdisciplinary, multi-centre project funded by MRC (Medical Research Council) in partnership with the technology company, Tokyo Electron Ltd, which now has a European base in Stevenage, UK. The project will combine stem cell technology, cell phenotyping, imaging, flow cytometry and automation to address a workplan entitled, “Development of metrics and quality standards for scale up of human pluripotent stem cells”.
This post will be based in Nottingham but will collaborate with a total of 5 researchers funded via this project across the consortium, comprises Nottingham, Manchester, the UK Stem Cell Bank, the University of Cambridge and the Wellcome Trust Sanger Institute, in addition to Tokyo Electron Ltd.
The overarching goal of the project is to address the need for developing human pluripotent stem cells (hPSCs) as off-the-shelf allogeneic products that are affordable to public/private health care systems. This requires quantifiable metrics that can measure the ‘health’ of hPSCs produced by automated platforms, such as a bespoke Tecan robotics system in Nottingham and a novel system developed by Tokyo Electron (EU base in Stevenage). The metrics to be developed will include phenotyping to quantify protein expression by multi-colour flow cytometry in the undifferentiated cells and to quantify the ability to engage in multi-germ layer differentiation. In addition, other partners in the consortium will perform array CGH and epigenetic profiling, as well as both discovery and targeted secretome metabolite/proteome analysis. These analyses will enable development of new biomarkers based on culture medium analysis (secretome, biosensor data) to refine culture conditions and generate new media/substrate combinations. Collectively, this will allow production of highly quality controlled populations of hPSCs on full automated robotic platforms for use in biomedicine.
The successful candidate will combine excellence in research, collaboration, communication and meeting deadlines with knowledge of one or more of these areas, including: human pluripotent stem cells, including understanding their pluripotency and early germ layer differentiation; flow cytometry analysis and cell sorting (preferably multi-colour); microarray / bioinformatics (with Pluritest Illumina microarray and TaqMan® hPSC Scorecard™ assays as an advantage); high content imaging platforms; automated liquid handling platforms; working with industry
Main Responsibilities / % time1. / Work collaboratively within a research-active team at the University of Nottingham (includes researchers and PhD students), and with academic / commercial partners in Manchester, the UK Stem Cell Bank, the University of Cambridge and the Wellcome Trust Sanger Institute, in addition to Tokyo Electron Ltd. This work will contribute towards producing quantifiable metrics that can measure the ‘health’ of hPSCs produced by automated platforms. / 60%
2. / Prepare data, reports and presentations for international project meetings held by video conference every 1-2 months and face-face every 3-4 months at the different partner institutions. The candidate will excel and achieving milestones / deadlines, which will be evaluated every 6 months. / 20%
3. / The post may be required to travel to the partner institutions to promote researcher and knowledge exchange between partners. / 10%
4. / Contribute to day to day development and running of the Denning Group, and to manuscript preparation and conference presentations / 10%
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 / DesirableQualifications/ Education / · Good first degree or equivalent in a relevant discipline
· PhD (or close to completion) in Biological Sciences or Engineering equivalent / · Relevant postgraduate qualification i.e. Masters
Skills/Training / · A proven ability to prepare and publish in excellent journals.
· Work productively in several of the areas below:
o human pluripotent stem cells
o understanding hPSC pluripotency and early germ layer differentiation in vitro or in vivo
o Flow cytometry (including sorting) experience – preferably multi-colour
o Experience of Pluritest Illumina microarray and TaqMan® hPSC Scorecard™
o Experience with high content imaging platforms
o Experience with automated liquid handling platforms
o Experience with work with industry
· 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 / · Skills in differentiating stem cells into various cell types, which may include cardiomyocytes, hepatocytes or neurons.
· Expertise in working with complex and / or automated equipment, such as robotic platforms
· Proven ability to teach, e.g. to PhD or Masters levels students
· Evidence of excellence within the field, such as awards and prizes
· Knowledge of the biotech industry
Other / Willingness to adopt the Ethos and Principles of the School of Medicine to improve the student experience.
Decision Making
i) taken independently by the role holder
Day to day research activity and planning including:· Planning general research programme and direction.
· Making individual/team decisions about design and conduct of particular experiments.
· To assist in preparing applications for new research funding.
· Maintenance and repair of equipment and apparatus.
· Advice on consumable and small scale purchasing.
ii) taken in collaboration with others
· Collaboration visits to project partners· Collaborative research applications.
· Direction of students/collaborators research and coordination of work effort.
· Investigation and decisions about new apparatus/equipment for the group.
· Publication decisions, papers, conference abstracts etc.
· Proposals for grant application.
· Overall direction of research and strategy for long term research programme.
iii) referred to the appropriate line manager by the role holder
Development of the research programme will be discussed with line manager, Prof. Chris DenningAdditional Information
Scope of the RoleTo 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 pluripotent 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.
Project Overview:
In addition to the synopsis above, an abstract of the research is provided below:
Expansion and banking of "off the shelf" allogeneic human pluripotent stem cell (hPSC)-derived lineages poses a realistic option for tissue repair, affordable to public/private health care systems. However, the regenerative medicine community currently lacks affordable and scalable systems. This bottleneck for translational programmes requires novel solutions as a matter of urgency, with the availability of clinical grade human embryonic stem cell, and in the near future human induced pluripotent stem cell lines. The overarching goal of this proposal is the development and qualification of a novel system for the automated scale up of hPSCs invented by Tokyo Electron (EU base in Stevenage), for subsequent differentiation into therapeutically valuable lineages. The novel, entirely enclosed, automated culture system suitable for next generation stem cell therapy manufacturing will use non-invasive image evaluation and non-invasive biochemical/genetic monitoring to allow evaluation of cell health and phenotype during cell expansion. Thus, only healthy cells can be selected for continued culture or entry into therapeutic differentiation protocols. In this proposal we will develop the metrics to ensure optimal conditions for stable expanded hPSC culture, including growth rates/phenotype and karyotypic/epigenetic normality. Deep phenotyping will include cell morphology via refinement of computer algorithms, genetic (e.g.CGH array) and epigenetic profiling and both discovery and targeted secretome metabolite/proteome analysis. Pluripotency will be assured via development of high throughput novel differentiation marker analysis replacing teratoma formation. We will generate new biomarkers based on culture medium analysis (secretome, biosensor data) to refine culture conditions and generate new media/substrate combinations. We will deliver online/Cloud-based metrics analysis tools available to UK/ other stem cell communities adaptable for other scale up applications.
Primary location of post:
The Research Associate/ Research Fellow in Translational Stem Cell Technology & Automation advertised 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.
Further information can be obtained from
Appendix 1
Department of STEM
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 (joining from University of Cambridge on 1st July 2015) to lead a programme on hPSC differentiation in lung and gut lineages. Dr. Cathy Merry (joining from University of Manchester on 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/ 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.