Research Scientist in Synthetic Biology

wei xin jie tu

 

    Job description and selection criteria

Job title

Research Scientist in Enzyme Evolution and Biocatalysis 

Research topic

Engineering Monooxygenase Enzymes for Selective Oxidation of Organic Compounds

Division 

Environment and Biotechnology (Molecular Science Group)

Reporting to

Professor Luet Wong

Group website

 

Salary Range

A competitive remuneration package will apply

Hours

Full time 

Contract type

Fixed-term (2.5 years), with the possibility of extension 

Start date

20 November 2020

Application closing date

31 October 2020

Vacancy reference

6007-2020-1

Additional information

Enzyme engineering, biotransformation, compound purification and characterisation, computational approaches

The role

The OSCAR research scientist (RS) in enzyme evolution and biocatalysis will join an established team developing engineered variants of cytochrome P450 enzymes for selective oxidation of organic compounds for applications in the synthesis of high-value intermediates and active ingredients for the fine chemical and pharmaceutical industries. The post is tenable for 2.5 years starting 1 November 2020. The RS will report to Professor Luet Wong, the joint-PI (with Professor Jeremy Robertson) of the programme.

The RS will design, prepare and test P450 enzyme variants for their regio- and stereoselectivity for the oxidation of C–H bonds of small molecule substrates. These typically contain 10–20 heavy atoms, including heteroatoms (N, O, etc.). Following screening of substrate classes against the enzyme collection, the RS will isolate the major oxidised products from scaled-up reactions using various chromatographic methods and characterise them by a combination of standard analytical techniques, primarily nuclear magnetic resonance spectroscopy and mass spectrometry. Isolated, characterised products will provide reference samples for further rounds of screening and mutagenesis, synthetic intermediates for further elaboration to targets of interest, and new potential components of pharmaceutical and agrochemical screening libraries via collaboration with other RS team members engaged in synthesis. The RS will analyse the mutation-selectivity relationships and design strategies for further evolution of the enzymes for enhanced turnover activity and product selectivity. To deliver the rapid turnaround between cycles of mutagenesis, product characterisation and target identification, the RS must have extensive experience and be effective in mutagenesis design, enzyme evolution, scaled-up biotransformation (up to gram scale) in vitro and in whole cells, and purification and characterisation of organic compounds. The ability and willingness to participate in technology transfer to industrial partners is essential.

Responsibilities/duties 

 

  • Manage own research and small-scale project management, co-ordinate multiple aspects of work to meet deadlines.
  • Adapt existing and develop new techniques and experimental protocols.
  • Use specialist scientific equipment in a laboratory environment. 
  • Test hypotheses and analyse results from a variety of experiments, reviewing and refining working hypotheses as appropriate to advance the project.
  • Collaborate in the preparation of scientific reports and journal articles.
  • Act as a source of information and advice to other members of the team on scientific protocols and experimental techniques.
  • Supervisory role for visiting students associated with the programme.
  • Represent the research group at external meetings/seminars, either with other members of the research team or alone.
  • Carry out collaborative projects with industrial partners.

Selection criteria

Essential

  • Hold a PhD or have submitted a PhD thesis prior to taking up the appointment, in monooxygenase engineering and biocatalysis.
  • Extensive experience and proven track record in the design and engineering of cytochrome P450 enzymes for the oxidation of unnatural substrates, especially heterocyclic compounds.
  • Extensive experience in both in vitro and whole-cell P450 biotransformation reactions at up to gram scale substrate conversion, and isolation and characterisation of oxidised products.
  • Have an excellent general knowledge of monooxygenase engineering and application in biotransformations, through reading of the literature, online database searching, and attendance at seminars and conferences.
  • Operate safely in the handling of biological and reactive reagents, have knowledge of associated reaction protocols, and able to prepare the required risk and hazard assessments appropriately.
  • Be familiar with routine methods for compound purification (manual and automated column chromatography, plate chromatography, crystallisation, distillation).
  • Be adept in performing spectroscopic methods for compound characterisation (1D and 2D NMR, MS, IR, polarimetry) and analysing the results.
  • Have excellent communication skills in English, in writing and in oral presentations.
  • Be able to demonstrate competence and success in the PhD thesis research area (and postdoctoral work where applicable). The assessors will seek evidence of a deep understanding of the applicant's previous fields of research and the applicant’s independent intellectual and practical contributions to previous research projects, as indicators that such attributes can be brought to bear on the present project.
  • Be viewed as a motivated, enthusiastic, organised self-starter who can work with a minimum of supervision but at the same time extract the benefits of an excellent research environment.
  • Show the ability to work supportively in a laboratory environment and take part in joint projects through co-operation and the exchange of information, skills and reagents.
  • Maintain detailed laboratory records and report on progress at regular intervals.
  • Be willing to learn new techniques and apply them in an interdisciplinary research environment to expand and improve technical and theoretical knowledge.
  • Have a track record of delivering research objectives against deadlines.
  • Have experience with or is aware of IP protection and confidentiality in research.

Desirable

  • Experience in basic organic synthesis (2–5 steps).
  • Experience in research supervision, e.g. of graduate students.
  • Experience in the use of automated chromatographies (e.g. HPLC) and related instrumentation (e.g. GC, LC-MS, SFC-MS).

Post-doctoral Research Scientist in Organic Synthesis – Further details

Applications are invited for a research position within the Molecular Science Group at the University of Oxford’s recently opened multidisciplinary research centre in China: the Oxford Suzhou Centre for Advanced Research (OSCAR: oscar.web.ox.ac.uk). This is an exciting opportunity to develop research activities in new laboratories fully equipped and resourced for synthetic biology, organic synthesis, and materials chemistry. Researchers in the Molecular Science Group (PIs: Moloney, Robertson, Wong) have dedicated new office and laboratory space, with adjacent analytical and spectroscopic equipment, including 400 MHz NMR, IR, UV, GC, GC-MS, analytical and preparative SFC-MS, GPC, and surface analytical and processing instrumentation. The work will be done in collaboration with research groups in Oxford and there will be the opportunity to undertake research visits there.

The current vacancy is for a Research Scientist at the post-doctoral level with a competitive remuneration package. The position is tenable from 1 November 2020, or as soon as possible thereafter, for 30 months in the first instance, with the possibility of extension.

The successful candidate will apply the methods of protein engineering and directed evolution to produce variant cytochrome P450 enzymes for selective C–H hydroxylation of a variety of small molecules for applications in the synthesis of natural products, their analogues, and new chemical entities for drug discovery and screening. Applicants should have significant expertise in P450 engineering and biotransformations with a demonstrated ability to design and execute mutagenesis strategies and optimize enzymatic hydroxylations on synthetically relevant scales; extensive expertise in compound isolation, purification, and spectroscopic analysis (especially NMR) will be essential. Training will be provided for equipment less familiar to the successful candidate. There will be opportunities to be involved in organic synthesis approaches for elaborating oxidised products and in computational approaches. Informal enquiries (but not applications) may be made to Professor Wong via email: luet.wong@chem.ox.ac.uk.

About OSCAR (Oxford Suzhou Centre for Advanced Research)  

OSCAR, the University of Oxford’s first overseas research centre, is working closely with the Suzhou Industrial Park and both academic and industrial collaborators in China to progress a range of exciting societal and economic development opportunities.

As a multidisciplinary research, innovation and technology centre, OSCAR focuses on research challenges and technologies that both complement the Centre’s location in Suzhou Industrial Park and capitalise on current Oxford research strengths. Research will initially be focused around the areas of biomedical engineering, biomedicine, advanced functional materials, electronic/ optoelectronic/ photonic devices, environmental technology, energy, mathematical and computational applications in finance and in health, and other related science and engineering disciplines.

The Centre is positioned in Suzhou Dushu Lake Science and Education Innovation District (SEID), a district in southern SIP with a high concentration of science, education and innovation activity. SEID is the archetype of higher education internationalization in China which hosts 32 local and foreign universities and institutions. The Centre, housed in a nine-storey building with a gross space of 20,000m2, offers flexible access to facilities for multi-functional activities such as labs, seminars, workshops, training, public events, and administration, etc. 

Guidance for Applicants

Thank you for your interest in applying for posts at the Oxford-Suzhou Centre for Advanced Research (OSCAR).

Before applying: 

Please read the job description and selection criteria carefully to determine whether you have the required skills, knowledge, and experience for the advertised role. Please DO NOT apply for the posts which are currently unavailable. We typically receive many applications for each post, so your cover letter should be used to show how you meet the essential and desirable criteria in order to be shortlisted for interview.

How to apply:

Send your application to info@oxford-oscar.cn

  1. Email subject should be the title of the post for which you are applying
  2. Include your contact information, name, telephone number and your availability for interview in the email
  3. Attach a cover letter and CV (both in English) as PDF documents.

 

Cover letter (no longer than one page):

Use the cover letter to explain your motivation for joining OSCAR, and state how your skills and experience match these requirements. Provide evidence that you have the skills, knowledge, experience, qualifications to meet the requirements of the post, with examples from previous work.

Curriculum Vitae (no longer than 8 pages):

Check that your CV is up-to-date, tailored to the job for which you are applying, and within the page limit. Highlight the skills and experience that are relevant to the post for which you are applying. Give details of your education, employment history, publication record, lists of prizes, and voluntary experience.

 

After applying:

The information you supply on your application will be provided to a selection panel, who will use it to assess your suitability for the post against the published selection criteria. You may be contacted via e-mail at any date regarding your application.

Your information is held securely in a database owned by OSCAR. The data will not be passed to external organisations or individuals other than those acting in a capacity as agents for OSCAR for software support purposes, or where an external body is party to the recruitment process.

When you submit an application to OSCAR you confirm that you agree to these Terms and Conditions of Use, including the following declarations:

  • The information provided in the application materials is true and complete. I understand that any offer of employment may be conditional upon satisfactory screening. 
  • I consent to be contacted by OSCAR at any date regarding my application. 
  • I consent to the information given in this application being stored and processed in accordance with the data protection rules at OSCAR. 

Thank you for your interest in applying for a post at OSCAR.

 

Recruitment Office

Oxford Suzhou Centre for Advanced Research

Email: info@oxford-oscar.cn