MAPCH1009 Research Fellow in Synthetic Organic Chemistry

Faculty of Mathematics and Physical Sciences School of Chemistry Research Fellow in Synthetic Organic Chemistry Fixed term for one year, available immediately Project title: Exploitin

Faculty of Mathematics and Physical Sciences

School of Chemistry

Research Fellow in Synthetic Organic Chemistry

Fixed term for one year, available immediately

Project title: Exploiting aldolases in the stereoselective synthesis of fluorinated products

The position is available to develop novel enzyme biocatalysts by protein engineering and directed evolution You will join a major research project funded by the Innovative Medicines Initiative that involves collaboration with scientists from academia and industry You will be supervised by Professor Adam Nelson (School of Chemistry) and Professor Alan Berry (School of Molecular and Cellular Biology) within the Astbury Centre for Structural Molecular Biology

You will have, or be about to obtain, a PhD in synthetic organic chemistry, and will have a strong interest in the development of enzyme biocatalysts You will also have excellent communication and IT skills Experience in solving problems in synthetic organic chemistry and a strong interest in biocatalysis are essential

University Grade 6 (£25,513 - £30,434 p.a.)

Informal enquiries may be made to Professor Adam Nelson, tel +44 (0)113 343 6502, email a.s.nelson@leeds.ac.uk Further information about the supervisors’ research may be found

at www.asn.leeds.ac.uk and www.astbury.leeds.ac.uk

Closing Date: 9 February 2015

Ref: MAPCH1009

Click here for further information about working at the University of Leeds

www.leeds.ac.uk/info/20025/university_jobs

Job Description

Responsible to: Head of the School of Chemistry

Reports to: Professor Adam Nelson

Professor Alan Berry when working in the Faculty of Biological Sciences

Purpose of the Post

The post arises from a major collaborative project funded from the Innovative Medicines Initiative Joint Undertaking under grant agreement n°115360, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution The collaboration spans academic institutions throughout Europe and involves a number of major pharmaceutic companies You will join the collaborative team led by Professor Adam Nelson and Professor Alan Berry, and will involve postdoctoral

researchers, PhD students, and scientists from the IMI collaborators The project will involve the development of new enzyme biocatalysts for the stereoselective synthesis of fluorine containing small molecule scaffolds The postdoctoral fellow will exploit aldolase enzymes as biocatalysts, and demonstrate their value in the synthesis of fluorinated building blocks The research will build

on the supervisors’ track record (see bottom of document) on engineering and exploiting aldolases

as biocatalysts

Main Duties and Responsibilities

 To exploit aldolase catalysts in the stereoselective synthesis of fluorinated building blocks

 To work under the direction of the project supervisors and under your own initiative

 To interact effectively with members of the research team including industrial and academic

collaborators nationally or internationally

 To communicate or present research results within the research team, at national and

international meetings and in learned journals

 To prepare concise written reports on the progress of the research, and to participate in regular meetings with the project supervisors and industrial collaborators at which the direction of the

research will be reviewed and planned

 To provide assistance to other members of the project supervisors’ research groups

 To maintain laboratory notebooks and experimental data professionally to underpin

publications and patents

 To assist in the preparation of publications and patents

 To assist in providing advice and training to other members of the project supervisors’ research

groups

 To contribute to, and to encourage, a safe working environment

 To contribute to routine laboratory housekeeping duties

 To undertake any other duties in relation to the research activities of the School, as directed by the supervisors of the research project, commensurate with the grade

 Any other duties as may reasonably be required, consistent with the grade of the post

Career Expectations

The University of Leeds is committed to developing its staff All staff participate in the Staff Review and Development scheme and we continue to work with individuals, supporting them to maximise their potential

Progression to a higher grade is dependent on an individual taking on an increased level of

responsibility Vacancies that arise within the area or across the wider University are advertised on the HR website - http://jobs.leeds.ac.uk - to allow staff to apply for wider career development opportunities

University Values

All staff are expected to operate in line with the university’s values and standards, which work as

an integral part of our strategy and set out the principles of how we work together More

information about the university’s strategy and values is available at

http://www.leeds.ac.uk/comms/strategy/

Person Specification

Essential

 PhD in synthetic organic chemistry, or will have submitted your thesis prior to taking up the position

 A strong interest in the development of enzyme biocatalysts

 Experience in solving problems in synthetic organic chemistry and a strong interest in biocatalysis

 Evidence of generation of publishable research in synthetic organic chemistry (e.g recent published papers in refereed journals)

 Experience in the use of modern spectroscopic methods to characterise synthetic

intermediates and products

 Ability to summarise research outputs/plans clearly and concisely in written reports

(supported in full by experimental data in publishable format)

 Demonstrable ability to show insight and judgement in independent planning of medium-term objectives and effective methods for delivering those objectives in a timely manner

 Ability to work in a highly organised and effective way as part of a collaborative research project

 Good background knowledge of contemporary research in synthesis organic chemistry

 Excellent IT skills

 Good interpersonal skills to enable effective communication with industrial collaborators with complementary expertise

 Commitment to and enthusiasm for research at the industry/academia interface

Desirable

 Demonstrable evidence of contributing to the preparation of publishable manuscripts

Additional Information

The University offers generous terms and conditions of employment, a wide range of benefits, services, facilities and family friendly policies Full details are available on the Human Resources web pages accessible at www.leeds.ac.uk/hr

The Partnership

The Partnership has been developed by students and staff and describes the mutual expectations

of us all as members of the University of Leeds community More information about the

Partnership is available at http://partnership.leeds.ac.uk

Disclosure and Barring Service Checks

A Disclosure and Barring Service (DBS) Check is not required for this position However,

applicants who have unspent convictions, cautions, reprimands and warnings, including any

pending criminal proceedings must indicate this in the ‘other personal details’ section of the

application form and send details to the Recruitment Officer at disclosure@leeds.ac.uk

Disabled Applicants

The post is located in the School of Chemistry Disabled applicants wishing to review access to the building are invited to contact the department direct Additional information may be sought from the Recruitment Officer, email disclosure@leeds.ac.uk or tel + 44 (0)113 343 1723

Disabled applicants are not obliged to inform employers of their disability but will still be covered by the Equality Act once their disability becomes known

Further information for applicants with disabilities, impairments or health conditions is available in the applicant guidance

Supervisors’ Track Record

1 Williams, G.J., Domann, S., Nelson, A and Berry, A (2003) Modifying the stereochemical

course of an enzyme-catalysed reaction by directed evolution Proc Natl Acad Sci USA,

100, 3143-3148

2 Woodhall, T., Williams, G.J., Berry, A and Nelson, A (2005) Synthesis of screening substrates

for the directed evolution of sialic acid aldolase: Towards tailored enzymes for the

preparation of influenza A inhibitor analogues Org Biomol Chem, 3, 1795-1800

3 Woodhall, T., Williams, G.J., Berry, A and Nelson, A.S (2005) Directed evolution of an aldolase

for the parallel synthesis of sialic acid mimetics Ang Chem Int Ed, 44, 2109-2112

4 Williams, G.J., Woodhall, T., Farnsworth, L.M., Nelson, A and Berry, A (2006) Creation of a

Pair of Stereochemically Complementary Biocatalysts J Am Chem Soc., 128,

16238-16247

5 Bolt, A., Berry, A and Nelson, A (2008) Directed evolution of aldolases for exploitation in

synthetic organic chemistry Arch Biochem Biophys, 474, 318-330

(doi:10.1016/j.abb.2008.01.005)

6 Campeotto, I., Bolt, A.H., Harman, T.A., Dennis, C., Trinh, C.H., Phillips, S.E.V., Nelson, A.,

Pearson, A.R and Berry, A (2010) Structural insights into substrate specificity in variants

of N-acetylneuraminic acid lyase produced by directed evolution J Mol Biol 404, 56-69

7 Kinnell, A., Harman, T., Bingham, M., Berry, A and Nelson, A (2012) Development of an

organo- and enzyme-catalysed one-pot, sequential three-component reaction

Tetrahedron.68, 7719-7722

8 N Timms, C L Windle, A Polyakova, J R Ault, C H Trinh, A R Pearson, A Nelson and A Berry (2013) Structural insights into the recovery of aldolase activity in N-acetylneuraminic acid lyase by replacement of the catalytically active -thialysine by using a

chemical mutategenesis strategy, ChemBioChem 14, 474-481

9 A Daniels, I Campeotto, M van der Kamp, A Bolt, C Trinh, S Phillips, A Peason, A

Nelson, A Mulholland and A Berry (2014) The reaction mechanism of N-acetylneuraminic

acid lyase revealed by a combination of crystallography, QM/MM simulation and mutagenesis,

ACS Chem Biol 9, 1025-1032