Research Duties - Workspace

Job Title:
Research Associate (CRYO-EM)
Molecular Sciences
Clinical Sciences
Job Family and Level:
Academic and Research, Level B
Salary Range:
£33,860- £42,830 per annum
Reporting To:
Dr Christian Speck
Working Closely:
Members of the DNA Replication research group
Wellcome Trust
Hammersmith Campus
Full time, fixed term for three years
Summary of Post
The DNA replication group, Imperial College London, is looking to recruit a Research
Associate interested in understanding how the eukaryotic replicative helicase promotes
accurate DNA replication using cryo-EM approaches.
One of the most fundamental property of all living things is the ability to replicate their DNA,
which allows cells to pass on their genetic material from parent to progeny. Five years ago,
Dr Speck’s lab achieved the reconstitution of eukaryotic replicative helicase loading with
purified Saccharomyces cerevisiae proteins and the identification of the MCM2-7 doublehexamer as a novel eukaryotic DNA replication complex (Evrin et al PNAS 2009). This led to
a series of discoveries: the identification of a multi-step MCM2-7 double-hexamer assembly
pathway and its regulatory circuits (Fernandez-Cid et al Mol Cell 2013; Evrin et al NAR
2013; Evrin et al NAR 2014), the first cryo-EM structures of a eukaryotic helicase loading
intermediate (Sun et al Nature Structure & Mol. Biology 2013), and the structural and
functional characterisation of the MCM2-7 double-hexamer (Sun et al Genes & Dev 2014).
We are now in a strong position to address two of the most fundamental questions in
eukaryotic DNA replication: how the replicative helicase becomes loaded onto DNA and
activated for DNA synthesis. Last year, we identified the MCM2-7 DNA-entry gate for
helicase loading, which is made up by the Mcm2 and Mcm5 subunits (Samel et al Genes &
Dev 2014). Now we want to address how this gates functions.
Project: The candidate will employ cryo electron microscopy to study the structure and
function of replicative helicase in the context of helicase loading and helicase activation in
collaboration with Richard Henderson (LMB Cambridge), Xiaodong Zhang (Imperial College
London) and Huilin Li (Brookhaven National Laboratory) (Sun et al Nature Structure & Mol.
Biology 2013; Sun et al Genes & Dev 2014). The candidate will have full access to the wellequipped cryo-EM facility at Imperial College. Regular use of a Titan Krios will be possible.
Crucially, the candidate will also have direct access to very good protein samples
(Fernandez-Cid et al Mol Cell 2013, Herrera et al NAR 2015) produced by group members,
which are ideally suited for high resolution cryo-EM.
This project will take into account the background and interests of the candidate and will
offer significant training opportunities. Altogether, this Wellcome Trust funded position will
offer opportunities to develop personally and professionally, a stimulating research
environment and deep insights into DNA replication and genome stability.
We offer:
• The possibility to work on a cutting-edge project using state-of-the-art technology in a
highly motivated research team
• A stimulating, diverse and international research environment
• Advanced training opportunities.
Samel AS, Fernández-Cid A, Riera A, Tognetti S, Herrera MC, Speck C (2014). A unique
DNA entry gate for regulated loading of the eukaryotic replicative helicase onto DNA. Genes
& Development, Aug 28:1653-1666
Herrera MC*, Tognetti S*, Riera A, Zech J, Clarke P, Fernández-Cid A, Speck C (2015). A
reconstituted system reveals how activating and inhibitory interactions control DDK
dependent assembly of the eukaryotic replicative helicase. Nucleic Acids Research, Sep 3
* Shared first authorship
Sun J*, Fernandez-Cid A*,Riera A*, Tognetti S, Yuan Z, Stillman B#, Speck C#, Li H#
(2014). Structural and mechanistic insights into Mcm2-7 double-hexamer assembly and
function. Genes & Development, Oct 15;28(20):2291-303
* Shared first authorship # Corresponding author
Sun J*, Evrin C*, Samel S, Fernández-Cid A, Riera A, Kawakami H, Stillman B#, Speck C#,
Li H# (2013). Architecture of the eukaryotic replication-licensing complex OCCM formed by
ORC-Cdc6 and Cdt1-MCM2-7 on DNA. Nature Structure & Molecular Biology, August 5,
(20), 944–951
*Shared first authorship # Corresponding author
Fernández-Cid A, Riera A, Tognetti S, Herrera MC, Samel S , Evrin C, Winkler C, Gardenal
E, Uhle S, Speck C. (2013). An ORC/Cdc6/MCM2-7 complex is formed in a multistep
reaction to serve as a platform for MCM2-7 double-hexamer formation. Molecular Cell, 18
April, Volume 50, Issue 4, 577-588
Evrin C, Clarke P, Zech J, Lurz R, Sun J, Uhle S, Li H, Stillman B, Speck C (2009). A
double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic
DNA replication. Proc Natl Acad Sci U S A. Dec 1;106(48):20240-5
Research Duties:
To generate reagents for the project
To design and carry out scientific experiments in accordance with the project
To maintain highly organised and accurate records of experimental work
To prepare material for presentation in oral and poster formats and present findings to
colleagues and at conferences
To contribute to writing bids for research grants
To analyse, manage and communicate data, ensuring the validity and reliability of the
data at all times
To draft publications and prepare them for submission to refereed journals
To submit publications to refereed journals
To actively contribute to the smooth running of the laboratory in co-ordination with other
members of the group
To form a good working relationship with other members of the group and actively
participate in team work
To promote the reputation of the group, Centre, the Department and the College
To develop contacts and research collaborations within the Centre, the College and the
wider community
To supervise staff, as appropriate, and to provide guidance and occasional supervision
to junior members of the laboratory, if requested
To actively participate in the group’s research meetings and academic activities
organised by the Institute (including internal seminars, lectures, institute retreats and
public-related activities)
To take initiatives in the planning of research
To identify and develop suitable techniques for the collection and analysis of data
To conduct data analysis
To write reports for submission to research sponsors
To present findings to colleagues and at conferences
To provide guidance to staff and students
To attend relevant workshops and conferences as necessary
To provide guidance to PhD students
To maintain highly organised and accurate record of experimental work
To actively participate in the research programme of the Group and Unit
To publish in high quality journals and to present data at national and international
To collaborate with other allied scientists within Imperial College and elsewhere in
London and abroad, as appropriate
To contribute to the smooth running of the Group’s/Unit’s laboratories and facilities with
other scientists, clinicians, technicians and students within the laboratories
To comply with the College, Division, and Unit safety practices and to attend courses on
safety when appropriate
Any other duties as may be deemed reasonable by Head of group as well as Head of
Other Duties:
To undertake appropriate administrative tasks as required
To undertake any necessary training and/or development
To maintain an up to date knowledge of relevant statutory Health and Safety legislation
and recommendations and attend safety training as required.
To observe and comply with all College policies and regulations, including the key
policies and procedures on Confidentiality, Conflict of Interest, Business Continuity,
Data Protection, Equal Opportunities, Ethics related, External Interests, Financial
Regulations, Health and Safety, Imperial Expectations (for new leaders, managers and
supervisors), Information Technology, and Smoking.
To undertake specific safety responsibilities relevant to individual roles, as set out on
the College Health and Safety Structure and Responsibilities web page:
Job descriptions cannot be exhaustive and the post holder may be required to
undertake other duties, which are broadly in line with the above key responsibilities.
Imperial College London is committed to equality and valuing diversity.
Imperial Expectations
These are the 7 principles that Imperial leaders, managers and supervisors are expected to
Champion a positive approach to change and opportunity
Communicate regularly and effectively within, and across, teams
Consider the thoughts and expectations of others
Deliver positive outcomes
Encourage inclusive participation and eliminate discrimination
Support and develop staff to optimise talent
Work in a planned and managed way
Applicants are required to demonstrate that they possess the following attributes:
A PhD in Structural Biology, Biochemistry or equivalent experience
Strong academic track record
At least one first-author publication in an internationally recognised peer-reviewed
journal (published or submitted)
Strong background in Electron Microscopy
Experience in sample preparation, structural analysis and data analysis
Strong background in protein expression and purification
Skills and Abilities:
Capable of working in a team, but able to plan and work independently
Excellent communication skills and fluency of the English language
Ability to critically review project progress, and to provide intellectual input into the
continued development of research
Ability to conduct a detailed review of recent literature
Ability to develop and apply new concepts
Excellent analytical skills
Creative approach to problem-solving
Ability to plan ahead and organise time effectively
Ability to accurately document work and keep clear records of the experiments being
Good working knowledge of standard software and scientific applications.
Strong attention to detail and focus on high quality work
Excellent verbal communication skills and the ability to deal with a wide range of people
Excellent written communication skills and the ability to write clearly and succinctly for
Ability to organise own work with minimal supervision
Ability to prioritise own work in response to deadlines
Advanced computer skills, including word-processing, spreadsheets and the Internet
Strong attention to detail and focus on high quality work
Ability to work constructively, open minded and effectively within a small team
Excellent organisational skills are required
Willingness to work flexible hours as work demands
Willingness to travel both within the United Kingdom and abroad to conduct research
and attend conferences
Proactive and flexible attitude to work with the ability to learn new concepts and