IMPERIAL COLLEGE LONDON JOB DESCRIPTION Job Title: Research Associate in Genetics & Molecular Biology Department: Molecular Sciences Institute: 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 Funding: Wellcome Trust Location: Hammersmith Campus Contract: 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 yeast genetics and in vivo replication analysis. Background: 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). Description: 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. Yeast genetics and in vivo replication analysis: The candidate will employ a novel chemical biology tool (Samel et al Genes & Dev 2014) to interrogate the requirements and function of the Mcm2/5 gate DNA entry during DNA replication and to identify replication factors that associate and regulate MCM2-7 ring opening in vivo. 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 References: 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 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, 577588 Evrin C, Clarke P, Zech J, Lurz R, Sun J, Uhle S, Li H, Stillman B, Speck C (2009). A doublehexameric 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 conduct and plan own scientific work with appropriate supervision 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 meetings 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 Division/Department/Section 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: www.imperial.ac.uk/safety/policies/organisationandarrangements. 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. PERSON SPECIFICATION Imperial Expectations These are the 7 principles that Imperial leaders, managers and supervisors are expected to follow: 1) 2) 3) 4) 5) 6) 7) 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: Qualifications: Essential A PhD in Biochemistry, Genetics, Molecular Biology or equivalent experience Strong academic track record Knowledge/Experience: Essential At least one first-author publication in an internationally recognised peer-reviewed journal (published or submitted) Strong interest in the area of DNA replication and genome integrity Strong background in Molecular Biology Experience in ChIP, Immune precipitations and cell cycle analysis Previous experience in supervising and training other researchers (e.g. students) Desirable Background in Yeast Genetics or Biochemistry Background in Bioinformatics Experience in the areas of DNA replication, DNA repair, the chromatin field, and the broader area of genome stability Skills and Abilities: Essential Capable of working in a team, but able to plan and work independently Excellent communication skills and fluency of the English language Strong attention to detail and focus on high quality work Ability to work constructively, open minded and effectively within a small team Highly motivated and committed individual with clear goals Proactive and flexible attitude to work with the ability to learn new concepts and technologies Excellent organisational skills are required 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 performed Good working knowledge of standard software and scientific applications 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 publication Ability to direct the work of a small research team and motivate others to produce a high standard of work 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 Other Willingness to work unsociable hours as work demands from time to time Flexible attitude towards work Willingness to travel both within the United Kingdom and abroad to conduct research and attend conferences The candidate should be highly ambitious and will aim to develop and publish major research projects