Astbury Centre for Structural Molecular Biology
Faculty of Biological Sciences
Research Fellow - Membrane Protein Structure Initiative (MPSI)
A BBSRC-funded postdoctoral post is available immediately, for 3 years in the
first instance, to elucidate the structures of membrane transport and channel
proteins. These play vital roles in biological processes ranging from nutrient
uptake to cell communication and many are critical drug targets. The
molecular mechanisms of these proteins will be analysed through a structural
genomics approach combining high throughput (HTP) protein expression, Xray crystallography and cryo-EM. A consortium of 8 UK Universities and
Research Centres are participating in this 5-year project for the BBSRC
SPoRT Initiative: at Leeds the focus is membrane protein expression,
purification, crystallisation and structure determination. This post is mainly
concerned with the crystallization and X-ray crystal structure determination of
prokaryotic membrane transport proteins. A PhD in a relevant subject area
and a strong research background in protein crystallography are required,
together with the ability to work independently.
Research IA (£22,289 to £25,565 p.a.), depending on qualifications and
experience
The University is introducing a new reward framework which will
facilitate the recruitment, retention and motivation of world class staff.
Informal enquiries to Prof. Simon Phillips, tel 0113 343 3027, email
s.e.v.phillips@leeds.ac.uk or Prof. Steve Baldwin, tel 0113 343 3173, email
s.a.baldwin@leeds.ac.uk
To apply online please visit http://www.leeds.ac.uk and click on 'jobs'.
Application packs from Alex Bateman, Faculty Staff Recruitment Office, Room
10.118, Level 10, Worsley Building, tel 0113 343 7493 email
fbsjobs@leeds.ac.uk
Job ref 313030 Closing date 31 December 2005
Further Particulars
Responsible To: Dean of the Faculty of Biological Sciences
Reports To: Prof Simon Phillips/Prof Steve Baldwin
The Membrane Protein Structure Initiative (MPSI)
Background to the post
The post is supported by a major research grant, as part of the BBSRC SPoRT
Initiative, to a consortium of researchers at the Universities of Glasgow, Leeds,
Manchester, Oxford, London (Imperial College and Birkbeck) and Sheffield,
together with the CCLRC Daresbury Laboratory. The grant supports a large
scale structural genomic study of membrane transport and channel proteins.
These proteins play vital roles in biological processes ranging from nutrient
uptake to cell signalling and communication and are of critical importance as
drug targets. The project aims to gain an understanding of the molecular
mechanisms of these proteins through a combination of high throughput protein
expression, X-ray crystallography and cryo-EM. Consortium participants at
Leeds are Professors Steve Baldwin, Simon Phillips, Peter Henderson, Mike
McPherson, John Findlay and Paul Knox. The focus of consortium efforts at
Leeds is large-scale, high-throughput membrane protein expression and
purification, with a component of crystallization and structure determination. The
post currently available is for crystallization and structure determination of
membrane transporters.
Summary of the research programme
Membranes lie at the interfaces between cells and their environment, and
between subcellular organelles and the cytosol. They therefore play critical
roles not only at the cellular level, but also at the level of tissues, organs and
the whole organism. These roles include energy transduction, communication,
nutrient acquisition, drug resistance (in humans), antibiotic resistance (in
pathogenic organisms), motility and immune defence. In all these roles
membrane proteins, including transporters and channels, are the key players.
Their biological importance is highlighted by the profound effects of genetic
deficiencies in these proteins such as occur in cystic fibrosis. Located in the
barrier surrounding cells, channels and transporters also represent important
targets – more than half of current drug targets are membrane proteins.
Given the key roles of membrane proteins described above, it will clearly be
necessary to understand their structures, and thence mechanisms and
regulation, at the molecular level if we are to understand how cells and
networks of cells function together in integrated ways in tissues, organs and
whole organisms. However, despite the fact that at least 30% of each known
genome encodes membrane proteins, the structures of less than 100
membrane proteins are currently known, in stark contrast to approximately
twenty thousand PDB entries for soluble proteins. This situation reflects
difficulties in membrane protein expression, purification and crystallisation that
have hampered research until recently. Fortunately, with improvements in
instrumentation and experimental techniques, the determination of membrane
protein structures has become more tractable. It is as a result of these
exciting advances that the current project has been made possible.
The Membrane Protein Structure Initiative (MPSI) is a consortium formed by
highly experienced and successful membrane protein research groups in
order to use their collective breadth and depth of experience and techniques
to develop strategies for high throughput (HTP) expression, purification,
characterisation, crystallisation and structure determination of selected
integral membrane proteins. The overall strategy is to address a target list of
membrane protein structures, with some tasks concentrated in specific nodes
of expertise and others distributed dynamically to make the most efficient use
of skills, resources and facilities. Examples of nodes of technical and
biological expertise are: University of Glasgow – protein purification;
University of Leeds - protein expression and purification; Imperial College –
protein crystallisation; University of Manchester – ABC transporters;
Daresbury Laboratory – X-ray data collection and Laboratory Information
Management System (LIMS)/data handling; University of Sheffield – HTP
electron microscopy; University of Oxford – modelling and simulation. The
overall aims include development of robotics and recombinational cloning
strategies for HTP production of expression constructs, development of HTP
screening methods for expression, solubilisation and purification, with
subsequent production of large numbers of purified proteins on >10mg scale
for crystallisation and structure determination, and HTP modelling of
homologues. Expression constructs, purified proteins and crystals will be
distributed around the consortium, according to available resources, expertise
and manpower, and data will be shared via a common LIMS database. The
ultimate outcome will be the production of a generic strategy linking the
identification of genes to a structural knowledge of the encoded membrane
proteins, and thence to a greater understanding of key biological processes.
Research environment
The Faculty of Biological Sciences at the University of Leeds is very large and
varied, and carries out high quality research in fields ranging from biophysics to
"whole organism" biology. A particular strength lies in the area of Membrane
Biology: as the result of a major SRIF2 award researchers working in diverse
areas of this field from cell biology and physiology to structural biology of
membrane proteins are located in contiguous laboratory space, forming a
Centre for Integrative Membrane Biology. The Faculty is also the major
component the interdisciplinary Astbury Centre for Structural Molecular Biology
(ACSMB), that additionally encompasses elements of the Schools of Chemistry
and Physics, and the Faculty of Medicine. In addition to work on membrane
protein structure (led by Profs. S.A. Baldwin, P.J.F. Henderson, J.B.C. Findlay
and Dr. M.A. Harrison), ACSMB encompasses groups working in X-ray
crystallography (Profs. S.E.V. Phillips, Drs. T.A. Edwards & M.R. Parsons),
protein engineering and design (Prof. M.J. McPherson and Dr. A. Berry), NMR
spectroscopy (Prof. S.W. Homans), electron crystallography (Prof. J. Trinick,
Drs. N.A. Ranson & P. Knight), protein folding (Prof. S.E. Radford), and
bioinformatics (Drs. D. Westhead, R. Jackson and M. Parker). These groups are
well integrated in terms of exchange of personnel and collaboration on projects
of common interest.
Facilities
Excellent facilities for large-scale membrane protein expression, purification and
crystallisation. These have recently been further enhanced by awards from SRIF
to establish a Membrane Protein Genomic Facility and from JIF to establish a
Centre for Biomolecular Interactions. Both of the latter are located in the Astbury
Building. Of particular relevance to the project are a state-of-the art fermentation
facility (currently comprising one 25L fermenter, two 30 L fermenters and shortly
to be equipped with a 70L fermenter), an MWG liquid handling robot for clone
construction and protein expression trials. Crystallization trials are supported by
a Hamilton liquid-handling robot for screen construction, a Douglas Instruments
crystallisation robot and an automated system for imaging crystal plates will be
purchased shortly (currently in tendering exercise) . Additional dedicated
equipment funded by the MPSI grant, has ensured that the facilities available for
the project are outstanding. The crystallographic group is equipped to
international standards, with three rotating-anode X-ray generators, two Rigaku
X-ray image plate systems (one Raxis-II and one Raxis-IV) and a
Siemens/Xentronics X-ray area detector system, all systems being equipped
with crystal cryocoolers. Computing facilities are very powerful, with a cluster of
Alpha-AXP workstations and multi-processor servers, 22 Silicon Graphics
workstations and servers and a powerful, new 160 processor Beowulf cluster.
Relationships
You will be formally responsible to the joint co-ordinators of the project at Leeds,
Profs. Baldwin and Phillips and, ultimately, to the Dean of the Faculty (Prof. A.J.
Turner). However, day to day management of specific aspects of the work may
be associated with individual members of the management team (Baldwin,
Phillips, Henderson, McPherson, Findlay and Knox) as directed by the coordinators in consultation with the entire management team.
The Faculty of Biological Sciences
The Faculty of Biological Sciences at the University of Leeds is one of the
largest in the UK with a total research grant portfolio approaching £70M and
an annual research spend of approximately £17M. Our research activities
have considerable breadth and depth with key strengths spanning molecular,
cellular, organism and population biology, with a significant focus on
multidisciplinary research.
Research within the Faculty is coordinated within Research Groups that are
clustered into three Research Institutes: The Institute for Integrative &
Comparative Biology (IICB), the Institute for Membrane & Systems Biology
(IMSB) and the Institute for Molecular & Cellular Biology (IMCB).
Each
Research Institute consists of approximately 50 academic staff and their
research teams. The breadth of our activity is illustrated by the subject areas
represented by the research groups: Ecology & Evolution, Genetics &
Genomics and the Centre for Plant Sciences which form the IICB; Membrane
Biology, Neurosciences, Cardiovascular Biology and Sport & Exercise
Sciences which make up the IMSB; Structural Molecular Biology, Molecular
Contractility, Molecular Cell Biology and Infection & Immunity which together
form the IMCB.
Collaborations across the Faculty are facilitated by an environment where low
walls between the Research Institutes and central Faculty research facilities
enable close interactions between researchers. We currently have over 230
postdoctoral staff and more than 300 PhD and MRes students who contribute
to the dynamic and vibrant research culture. The breadth of our research
strengths help create an intellectually stimulating and exciting environment
which creates considerable opportunities for ambitious researchers wishing to
develop their research careers.
Job description
You will be required to carry out original research, as a member of a team with
the common objective of the HTP structural analysis of membrane proteins.
Although the research will be directed by the management team, you will be
responsible for the day-to-day organisation of your own part of the research
project, and is expected to show considerable independence in its
implementation and design. You will also be responsible for updating the
appropriate parts of the LIMS. In addition to carrying out the research and
regularly presenting the resultant data at scientific meetings and in the form of
papers, you will participate in supervision of the technicians who are also
being funded by the BBSRC. The participation in the supervision of
postgraduate students working on the project is also required, as is the ability
to work as part of a larger team of scientists in busy research laboratories.
The specific duties associated with the post are as follows:
The post will primarily involve the crystallization and structure determination of
membrane transporters and channels. This will concern mainly, but not
exclusively, prokaryote proteins produced by the rest of the MPSI team at
Leeds. Techniques to be used will include automated crystallization screening
and preliminary X-ray diffraction studies, data collection and structure
determination using synchrotron radiation sources and structure refinement. In
addition, there will be opportunities to develop a novel method for generating
crystal scaffolds to aid in structure determination of proteins that do not
crystallize alone. The work will be in collaboration with, and complementary to,
studies by other team members both at Leeds and at the other participating
institutions, and will offer the opportunity of learning techniques for membrane
protein expression.
Person Specification
Qualifications
Essential

PhD in Biochemistry or related biological science subject
Desirable

1st class or 2i first degree (or equivalent) in Biochemistry or allied
science subject
Experience
Essential

PhD or post-doctoral experience in crystallization and structure
determination of proteins by X-ray crystallography
Desirable



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Research background in structural molecular biology
PhD or post-doctoral experience in the expression and purification of
proteins for structural studies
Practical experience of structure determination of membrane proteins or
of large and complex structures
Presentation of research results in the form of posters, papers or talks at
scientific conferences
Skills/Knowledge
Essential
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Effective practical skills at the laboratory bench
Excellent numerical skills for the appropriate interpretation of data
Excellent organisational skills to allow several aspects of the project to
be pursued simultaneously as well as organising team meetings,
workshops etc.
Excellent interpersonal skills: the ability both to work effectively as a
member of a team and to supervise the work of technicians and students
Effective communication skills both verbal and written (e.g. oral
presentations of research, preparation of papers for submission to
scientific journals)
Ability to use own initiative in determining the course of the research
project
Desirable

Familiarity with available tools for protein purification, crystallization and
structure determination and ability to advise others on their use

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Familiarity with software packages for protein structure analysis, and
molecular graphics
Good word-processing skills, preferably using Word for Windows
Ability to use spreadsheets and data analysis packages, e.g. Excel and
Origin
Ability to use presentation/drawing packages e.g. Powerpoint, Corel
Draw.
Personal Qualities
Essential

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Enthusiasm for research
Friendly and helpful manner
Commitment to producing and writing up publishable results
How to apply
Applications should include the following:


A completed application form
A Curriculum Vitae/information requested on page 2 of the form
Equal Opportunities Monitoring Form (Enclosed). Please return the
Form in a separate envelope (enclosed) marked 'EOs Monitoring'.
Replies will be treated in complete confidence.
Completed applications should be returned to Mr Alex Bateman, Faculty
Staff Recruitment Office, Faculty of Biological Sciences, University of
Leeds, Leeds, LS2 9JT, email a.bateman@leeds.ac.uk quoting job ref
313030 not later than 31 December 2005.
If you are selected for interview you can expect to hear from the University
not later than 4 weeks after the closing date. If you are not selected for
interview the University will not contact you again.
A Criminal Records Disclosure is not required for this position.
Disabled Applicants
The post is located in the Astbury Building, which is fully accessible. Disabled
applicants are welcome to review the building and its access. Additional
information may be sought from the Team Co-ordinator in Disability Services,
e-mail disability@leeds.ac.uk or tel 0113 343 3927.
Disabled applicants are not obliged to inform employers of their disability but
will still be covered by the Disability Discrimination Act once their disability
becomes known.
Data Protection
The information you provide in your application will be used to consider your
suitability for the post for which you have applied. If your application is not
successful the information will be disposed of confidentially within 8 months. If
your application is successful and you are appointed, your information and
future data will be processed in accordance with the University's Data
Protection Code of Practice. A copy of this code can be obtained from either
the University's Human Resources Department or by visiting
http://www.leeds.ac.uk/hr/policy/index.htm
Health and Safety Responsibilities
You are required to adhere and comply to the provisions of the Health and
Safety at Work Act, related Regulations and in accordance to the University’s
Policy on Health and Safety which can be accessed via
http://www.leeds.ac.uk/safety/usp/uspindex.htm
In addition you are also required to cooperate with regard to the
implementation of Health and Safety arrangements and should not interfere
with or misuse anything provided in the interest of Health, Safety and Welfare
at Work.
For more information on the University and terms and conditions of
appointments please visit http://www.leeds.ac.uk
RIA
The University of Leeds
Salary Scales
Research Staff Grade IA
With effect from 1 August 2005
£
20,044
21,156
22,289
23,182
24,352
25,565
26,470
27,929
28,829
30,002
The University of Leeds
Equality and Diversity Statement
The University of Leeds is proud to be a multi-cultural community. We value
diversity, and are determined to ensure:

that we treat all individuals fairly, with dignity and respect;

that the opportunities we provide are open to all;
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that we provide a safe, supportive and welcoming environment – for
staff, for students and for visitors.
We recognise that we still have work to do to secure a truly inclusive
community, and we are committed to a wide-ranging plan of action to tackle
discrimination and to promote diversity.
The Equality and Diversity Statement forms part of the University’s Equality
and Diversity Policy, which applies to staff and students alike and is available
on the University’s website at http://www.equality.leeds.ac.uk/ed/policy/
The University has published the following policy and code of practice which
are linked to the Equality and Diversity policy. They are also available on the
University’s website:


The Race Equality Policy,
The Code of Practice on Harassment and Bullying
Further policies are being developed, and will be made available on the
University’s website in due course.
Further information and advice are available from The Equality Unit,
Telephone: 0113 343 3927 or by email to equality@leeds.ac.uk
Removal Expenses
The University will contribute to removal expenses incurred by new members
of Academic and Academic-Related staff who:



accept a position for two years duration or more, which is University
funded,
accept a position that has been advertised nationally (this includes the
University website and jobs.ac.uk),
at the time of appointment (i.e. date of letter of appointment) live
outside a radius of 25 miles from Leeds (LS2) and who move to within
such a distance to take up the post.
Appointees based at the Bretton Campus must, in order to qualify, live outside
a radius of 25 miles from West Bretton (WF4) at the time of appointment and
should move to within such a distance to take up the post.
Claims may not cover conveyancing or estate agent's fees or other costs
involved in the relocation. Members of staff seeking such assistance should
contact the Recruitment Service for the details of approved contractors and a
copy of the University Removals Policy.
Key Principles
For qualifying staff the University will reimburse the cost of moving
household effects only (by surface freight), the cost of storage (up to a
maximum period of six months) and insurance costs (while effects are in
transit or storage). The costs must be reasonable and up to a maximum of
£5,000.
Staff joining the University from overseas on a University funded position, may
receive full reimbursement of economy class fares for all members of their
immediate family i.e. spouse/partner and children, together with reasonable
costs for removing household effects by surface freight. Receipted invoices
or other appropriate documentation should accompany all claims for removal
expenses.
Expenses are normally paid only in respect of an initial appointment and must
normally be claimed within 12 months of taking up the appointment.
The University is entitled to recover removal expenses for all staff who, at
their own volition, terminate their employment with the University within the
first 2 years of their contract. The University will not however seek to recover
such expenses from staff granted an ex gratia payment on a discretionary
basis i.e. staff on University-funded appointments of two years or less or staff
on outside-funded appointments.