UNIVERSITY OF NOTTINGHAM RECRUITMENT ROLE PROFILE FORM Job Title: Research Fellow School: School Pharmacy Salary: £28,695 - £32,277 per annum depending on skills and experience Job family and level: Research and Teaching Level 4 Hours of Work: Full-time, 36.25 hours per week Contract Status: Fixed-term contract for a period of 36 months starting 1 January 2016 Location: School of Pharmacy, University Park Reporting to: Professor Dave Barrett Purpose of the Role: To undertake research linked to the BBSRC ‘GASCHEM’ project. The role will join a team of interdisciplinary researchers at the University of Nottingham applying metabolic engineering and systems/synthetic biology to produce biofuel and high value chemical intermediates. The position will be based at the University of Nottingham and the successful candidate will work in the School of Pharmacy and have close links with GASCHEM researchers in the School of Life Sciences. The person appointed will be responsible for the development of new metabolic profiling methodologies and their application to understanding of key metabolic pathways in C. ljungdahlii using targetted (LC-MS/MS) and global profiling (UPLC-Orbitrap) methods. He/she will also undertake subsequent bioinformatic and metabolic pathway analysis. Candidates must have proven experience in analytical method development and in the design and implementation of metabolomics experiments. Candidates should hold a PhD or equivalent in analytical science, specialising in mass spectrometry. Proven experience in the fields of metabolic pathway profiling, metabolomics or bioinformatics would be desirable. The successful candidate should possess good project leadership skills and have excellent verbal and written communication skills. 1. 2. 3. 4. 5. Main Responsibilities Plan and conduct supervised research using recognised approaches, methodologies and techniques. This will include but is not limited to: To develop mass spectrometry methods to profile microbial metabolic pathways in C. ljungdahlii To co-ordinate and conduct targeted and global metabolite LC-MS and GC-MS analyses of biofluid samples To undertake bioinformatic data analysis and metabolic pathway analysis Develop research objectives and proposals for own and/or collaborative research area. Analyse and illuminate data, interpret reports, evaluate and criticise texts and bring new insights to research area. Prepare research work for publication and/or contribute to the dissemination to relevant groups including external bodies and conferences, resulting in successful research outputs. Assist in the preparation of scientific reports and publications for the grant programme. Identify opportunities and assist in writing bids for research grant applications. Prepare proposals and applications to both external and/or internal bodies for funding, 6. 7. 8. 9. 10. 11. 12. 13. contractual or accreditation purposes. Build relationships with both internal and external contacts in order to exchange information, to form relationships for future collaborations and identify potential sources of funds and/or opportunities for collaboration. Co-ordinate the operational aspect of research networks, for example, arranging meetings and updating web sites etc. and contribute to collaborative decision making with colleagues in area of research. Work in conjunction with others in the research team to achieve objectives and make an active contribution to the success of the team. Provide support, guidance and supervision to other staff, where appropriate in own area of expertise. Assist in the supervision of undergraduate and/or postgraduate students projects, fieldwork and placements, as appropriate. To participate in the assessment of student knowledge and co-supervise projects at Masters level. Collaborate with academic colleagues on areas of shared interest for example, course development, collaborative or joint research projects. Plan and manage own research activity and resolve problems, if required, in meeting own/team research objectives and deadlines in collaboration with others. Contribute to the organisation of research resources and facilities, laboratories and workshops as appropriate. Undertake general laboratory duties such as ordering of reagents, equipment maintenance, and laboratory housekeeping. Contribute to teaching, for example through laboratory demonstrations, lectures to postgraduate workshops and/or delivery of Level 1 modules. Person Specification: Qualifications/ Education Skills/Training Essential 1. A 1st or upper-second class honours degree in biochemistry, pharmaceutical sciences or a closely related subject and a PhD in metabolomics/mass spectrometry. 2. Training in bioinformatics software relevant to metabolomics Desirable PhD in bioanalysis/analytical science 3. Excellent oral and written communication skills including the ability to communicate complex information with clarity and write to a publishable standard. 4. Strong analytical skills including the ability to analyse and illuminate data, interprets reports, evaluate and criticise texts and bring new insights. 5. Ability to creatively apply relevant research approaches/models/ techniques/methods and devise and manage research programmes. 6. Excellent problem solving, IT and organisational skills including the effective deployment of resources. 7. Ability to build effective relationships as part of a team and collaborate with others, both internally and externally. Ability to interrogate databases to identify metabolite structures Ability to automate data acquisition and analysis Knowledge of bacterial metabolic pathways 8. Flexible, proactive and dedicated approach. 9. Ability to travel within the UK and overseas. Experience 10. Proven LC-MS and/or metabolomics experience GC-MS Biological mass spectrometry experience 11. Presenting work effectively to a variety of professional and academic audiences at meetings and conferences. Pathway analysis and flux analysis First author publications in high impact factor journals. Previous success in gaining support for externally funded research projects. Training and/or supervision of staff or students. 12. A consistent track record of published research in peer-reviewed journals and writing high quality reports and papers for publication. Statutory/legal Due to the requirements of the UK Border and Immigration Agency, applicants who are not UK or EEA nationals and whose immigration status entitles them to work without restriction in the UK will be considered on an equal basis with UK and EEA nationals. Other non-UK or non-EEA nationals whose employment will require permission to work subject to a resident labour market test may only be considered if there are no suitable UK or EEA national candidates for the post. Please visit http://www.ukba.homeoffice.gov.uk/ for more information. Informal enquiries may be addressed to Professor Dave Barrett [david.barrett@nottingham.ac.uk], tel 0115 951 5062) or Dr Klaus Winzer (klaus.winzer@nottingham.ac.uk, tel 0115 823 2247). Please note that applications sent directly to these email addresses will not be accepted. Equality and Diversity The University of Nottingham has a range of policies to promote equality and diversity in the workplace which are fully supported and promoted by the School through its Equality and Diversity Committee. The School welcomes applications from all candidates and you can read more about our commitment to equality and diversity at http://tiny.cc/UoNPharmEandD Background to project: GASCHEM: Optimising industrial gas fermentation for commercial low-carbon fuel & chemical production through systems and synthetic biology approaches A multidisciplinary project involving four postdoctoral researchers and up to 10 PhD students. Acetogenic Clostridium species, such as C. ljungdahlii, are able to capture carbon (in the form of CO or CO2) through anaerobic gas fermentation. As such they are able to grow on a spectrum of waste gases from industry (eg., steel manufacture and oil refining, coal and natural gas) as well as 'synthesis gas' (CO and H2) produced from renewable and sustainable resources, such as biomass and domestic/ agricultural wastes. This enables low carbon fuels and chemicals to be produced in any industrialized geography without the need to consume valuable food or land resources. Working with an industrial leader in the field, LanzaTech, we plan to use metabolic engineering to both better understand and thence optimize and extend product streams through a combination of systems and synthetic biology approaches. The exemplification of the Nottingham's pivotal gene technologies in C. ljungdahlii, coupled with LanzaTech expertise in gas fermentation now provide all of the necessary elements to undertake the following objectives. OBJECTIVE 1: To take a systems approach to understanding the metabolic pathways leading from gas uptake to its conversion to metabolites, focusing on the pathways that lead to ethanol (EtOH) and 2,3-butanediol (2,3BD) formation (Systems Biology: Year 1-3). OBJECTIVE 2: To use metabolic engineering to manipulate products streams to maximise either EtOH or 2,3BD for alternative jet fuel or chemical applications (Bioenergy: Year 2-4). OBJECTIVE 3: To extend the product range to more high value fuels and chemicals using a synthetic biology approach, initially focusing on iso-butanol and succinate (Synthetic Biology: Year 3-5). OBJECTIVE 4: To evaluate the modified strains in laboratory, pilot, and eventually, demonstration scale systems at LanzaTech facilities (Industrial Biotechnology: Year 4-5). These objectives will be progressed through a combination of disciplines (molecular genetics, biochemistry, fermentation technology, mathematical modelling) and will draw on the participation of a team of investigators expert in clostridial molecular genetics (Minton), clostridial fermentation and physiology (Winzer), systems biology (Hodgman) and mathematical modelling (King), analytical metabolomics (Barrett) and chemistry (Thomas). The outcome will be both to improve the commercial yields of existing fuels, (EtOH & 2,3BD) and to extend the versatility of the system through the sustainable production of non-native C4 products from pyruvate, specifically iso-butanol and the chemical building block succinate. Metabolite Analysis (main role for advertised position) Quantitative intracellular measurements of key metabolic pathway intermediates will be monitored under steady-state fermentation conditions using controlled cell lysis by freeze-thaw methodology to release intracellular metabolites and eliminate analytical crosstalk from extracellular components. The pathways involving polar (non-volatile) metabolite intermediates (to include the ‘one carbon’ metabolic pathway from CO/CO2 via THF to 5-methyl THF, acetyl CoA, pyruvate, acetolactate, 2ketoisovalerate, L-valine, succinate and TCA cycle metabolites) will be monitored using a specific, targeted liquid chromatography electrospray tandem mass spectrometry (LC-MS/MS) method by means of alky chloroformate derivatization or similar methodology. A robust and versatile derivatizing process will be developed capable of reacting with a wide range of chemical functional groups (amine, carboxylic acid, thiol, and hydroxyl) under aqueous conditions resulting in metabolite derivatives which have an excellent response in positive electrospray ionisation mass spectrometry. The Barrett group has recently established methodology to profile central metabolism E. coli and this analytical approach will be adapted for specific use in C. ljungdahlii metabolite profiling. Volatile fermentation products and intermediates (to include acetic acid, ethanol, 2,3butanediol and isobutanol) will be measured in the extracellular growth medium using gas chromatography-mass spectrometry (GC-MS). Where observations are required of any wider effects on metabolic pathways as a result of metabolic engineering (eg bottlenecks and competing pathways) then global metabolic pathway profiling methodology (metabolomics) will be used. An established ultrahigh performance liquid chromatography (UPLC) method coupled to accurate mass (orbital trap mass spectrometry) will be used to identify perturbations to intra- and extracellular metabolite pools. Reference to an in-house accurate mass database of Clostridia primary and secondary metabolites will aid in the rapid identification of these perturbed pathways.