SPECK LAB OVERVIEW
The objective of the group is to discover new mechanisms in the initiation and elongation of DNA replication and to understand the function of replication factors in hetero-chromatin formation. We have reconstituted the loading of the eukaryotic replicative helicase onto DNA, an essential step in DNA replication and use this system to address the mechanism and regulation of two key events: the loading of the eukaryotic DNA helicase onto DNA and the kinase dependent activation of the helicase. More recently, we have started to investigate the role of the helicase loading factors in epigenetic memory, which has important implications for human disease and aging.
Enquires from motivated and exceptional students and postdocs to work in the group are always welcome. Please send full CV and cover letter to: email@example.com
Postdoc position for 2018
A Wellcome Trust funded 3-year postdoc positions is available in the Speck-lab:
This is an ideal opportunity for an enthusiastic and creative scientist to join a dynamic research team with excellent collaborators and facilities. The successful applicant will use cutting-edge biochemical approaches to work on a high profile project investigating novel mechanisms in eukaryotic DNA replication with therapeutic potential.
The project will address a basic biology question: how do key DNA replication factors function and how they are regulated. This type of work is crucial to understand how cancer development is initiated and will serve as a stepping-stone for the future development of replication inhibitors with potential as chemotherapeutic drugs.
The main aim of the project is to discover how Cdt1 functions in MCM2-7 ring opening/closing and induction of ATP-hydrolysis, two key events during initiation of DNA replication. The research will involve design of constructs, expression and purification of proteins & protein complexes using bacteria and yeast.
This is the ideal time to join the Speck lab, as our recent cryo-EM work provided us with key structural insights into the helicase loading He/She will work together with lab members to obtain high resolution cryo-EM structures of several reaction intermediates. The candidate will be able to take advantage of well-developed protocols and methods. However, there is plenty of scope to develop novel creative biochemical assays, to set-up new procedures or apply biophysical approaches such as single molecule FRET. In vitro results will be confirmed using yeast genetics and chromatin binding assays.
The successful candidate will enjoy intensive interactions with group members specialised in cryo-EM, biochemistry or in vivo approaches generating a collaborative and highly productive atmosphere, with opportunities for advanced training.
This project will take into account the background and interests of the candidate and will offer significant training opportunities
The application deadline is 5 April 2018. A publication in a decent quality journal (submitted/published) is essential. Please follow the link for details and get in touch if you have questions (firstname.lastname@example.org).
- You have a fascination for discovery of fundamental biological mechanisms with medical relevance.
- You are self-motivated and like to target ambitious research questions.
- You do not become discouraged by technical problems, but employ troubleshooting to overcome specific issues.
- You enjoy working in a team in order to tackle larger projects, while adding to your first author publication record.
What’s on offer:
- Advanced training opportunities in a range of biochemical assays, protein purification methods, assay development, protein engineering and cryo-Electron Microscopy.
- The PI is mentoring group members in grant writing, project design and the writing of research publications.
- The expanding lab with highly motivated postdocs & students, excellent equipment & facilities provides an ideal setting to make the jump to the next career stage.
Major scientific accomplishments
- The cryo-EM structure of Mcm2-7 on DNA suggests a new lagging-strand DNA extrusion model (Proceedings of the National Academcy of Science of the United States of America, 2009)
- Elucidation of the MCM2-7 double-hexamer structure reveals key mechanism in helicase loading and activation (Genes & Development, 2014a)
- Identification of the DNA entry gate of the MCM2-7 helicase during helicase loading (Genes & Development, 2014b)
- Characterisation of the first structure of an eukaryotic replicative helicase in complex with its loading factors (Nature Structural & Molecular Biology, 2013)
- Identification of a novel ATPase dependent pre-RC intermediate that is surveyed by a quality control mechanism for genomic stability (Molecular Cell, 2013)
- Discovery of a pre-RC intermediate that forms in the absence of ATP-hydrolysis and contains one copy of all 18 pre-RC factors (Nucleic Acids Research, 2013)
- Reconstitution of pre-RC formation and discovery of the MCM2-7 double-hexamer as a central DNA replication intermediate (Proceedings of the National Academcy of Science of the United States of America, 2009)
- Identification of an ATPase-dependent mechanism that allows sequence specific recognition of the DNA replication origin (Journal of Biological Chemistry, 2007)
- Elucidation of the ORC-Cdc6 complex structure and its sequence specific origin binding activity (Nature Structural & Molecular Biology, 2005)
- Identification of key mechanism in initiation of DNA replication in bacteria (The EMBO Journal, 2001)
- Discovery of an ATP dependent mechanism to coordinate initiation of DNA replication with transcriptional regulation in bacteria (The EMBO Journal, 1999)
Funding (past and present)
The Group is or has been funded by the BBSRC, DFG, EPSRC, EU (ERASMUS, Marie Curie), Wellcome Trust, Leukemia & Lymphoma Society, Max Planck Society, and MRC.
Group News & Congratulations to ...
Sarah for being awarded a prestigious two year year Deutsche Forschungsgemeinschaft (DFG) Research Fellowship
Katalin for being selected for the 2017 EMBL-EBI course in Structural Bioinformatics.
Yasunori for being awarded a prestigious two year year Japan Society for the Promotion of Science (JSPS) Overseas Research Fellowship.
Chris Weekes joins the lab as a PhD student. Big welcome!
Group picnic on the scrubs. Quiche, pate, cake ... and even some sunshine!
Claire Rousseau from France joins the lab as a summer intern. Big welcome!
Katalin for raising funds for the Daphne Jackson Trust to support scientist to return after a career break.
Leonhard Karl from Germany joins the lab as an MSc student. Big welcome!
Marta for being awarded a Higher Education Academy Associate Fellowship
The London consortium for cryo-EM (LonCEM), of which the Speck lab is a founding member, was awarded £ 3 million by the Wellcome Trust to for high end cryo-Electron microscopy.
Katalin, who successfully applied towards the EMBO course on High-throughput protein production and crystallization.
Max for being awarded a prestigious two year Deutsche Forschungsgemeinschaft (DFG) Research Fellowship.
Indiana for receiving the CSC Local Hero Award.
Katalin Kondas join the lab as a Postdoctoral Daphne Jackson Fellow. Big welcome!
Group retreat in Norfolk at the Grange Manor House - lots of fun.
Henry for passing his MSc viva with distinction.
Marta for being awarded a bursary from the Biochemical Society UK for the 80th Harden Conference.
Alberto, who successfully applied for the Cryo-Electron Microscopy and 3D Image Processing course at EMBL
Christian has been promoted to Professor of Genome Biochemistry & Molecular Biology.
Alberto new toy, a graphics processing unit (GPU)-accelerated workstation, has arrived.
Katalin Kondas, who will join the Group in September, was awarded a two year Daphne Jackson Trust Fellowship.
Max Reuter joins the lab as a Postdoc. Big welcome!
Sarah new toy arrived - the FEI Vitrobot Mark IV.
Sarah Schneider and Yasanori Noguchi join the lab as Postdocs. Big welcome!
Silvia Tognetti, as the News & Views she wrote got published in Nature Cell Biology.
Marta and Indiana participated in the CSC microscopy workshop for local primary school children from Ark Conway Academy and Old Oak Primary School.
Christian gave an update of Athena SWAN progress of the institute and presented the mentoring awards at the annual retreat.
* NEW PHD POSITIONS AVAILABLE FOR 2017/2018 *
Imperial College PhD Scholarship Scheme I am considering now to sponsor an excellent UK, European or International candidate for the fully funded Imperial College PhD Scholarship Scheme - academic year 2017/2018. Please contact me directly to discuss potential research proposals (email@example.com).
3.5 YEAR MRC DTP Studentships Candidates with an interest in genomic stability, epigenetics and disease please contact Christian to discuss potential research proposals. Competitive candidates for each of these projects will hold a degree in biochemistry or closely related subject with an outstanding academic record and some practical research experience. Applications can be submitted online through the Imperial College website; informal enquiries (CV/covering letter) may be sent to Christian via email (firstname.lastname@example.org).
OTher positions available
Bachelor/ MRes/ Master Students (UK/EU/International)
Any students interested in pursuing research in our group should contact Christian Speck by email (email@example.com) for potential openings. Please send your CV and explain your interest in the specific research area. European/International students must obtain independent funding through ERASMUS or via a government bursary to cover their expenses.
Any students interested in pursuing postgraduate research in our group should contact me directly by email (firstname.lastname@example.org); all prospective applicants should have or expect to obtain a 1st class honours degree (or equivalent) in biochemistry, or a closely related discipline.
If you are interested in joining the lab as a postdoc please contact Christian Speck by email (email@example.com) sending your CV and explaining your interest in this specific research area. Outstanding PhD students are encouraged to make contact as early as possible to discuss potential fellowship applications, for example from the European Union, HFSP, etc.. Full assistance will be given in preparing a competitive research proposal with bridging funding being available to the candidates; we have an exceptional track record in accelerating the careers of outstanding postdoctoral researchers, with fellowships from Marie Curie, DFG and MRC awarded to members of our lab.
The SPECK LAB
About Dr. Christian Speck
Christian is a Professor of Genome Biochemistry & Molecular Biology at the Institute for Clinical Sciences in the Faculty of Medicine. He is a Fellow of the Royal Society of Biology (FRSB) and has been the recipient of two prestigious research fellowships from an US charity foundation and the Max Planck Society, research grants from the UK research councils, and received the Wellcome Trust Investigator award in 2015. Christian served as an invited panel member during the scientific evaluation of the Horizon 2020-MSCA-IF-2016- LIF and the French National Research Agency - ANR. He sits on the editorial board of the Journals Microbial Cell, Biochemical Journal, chairs the Institutes Athena Swan committee and sits on the Clinical Science Centre Postgraduate Education Committee. He has given oral presentations at the renowned Cold Spring Harbor DNA replication meeting for the last 10 years. Christian has been invited to numerous European and UK universities for research seminars and as a session Chair to the Cold Spring Harbor Replication meeting and the FEBS Congress . During his B.Sc. degree in biotechnology at the Beuth Hochschule of Berlin, Dr. Speck undertook a project at Genentech Inc in South San Francisco USA for 6 month in the laboratory of Dave Goeddel (CSO, Genentech) to get industry experience. Christian obtained his Ph.D. in biochemistry from the Free University of Berlin under the guidance of the late Prof. Walter Messer working at the Max-Planck institute of Molecular Genetics, while being funded by a Max-Planck Fellowship to study bacterial DNA replication. This work resulted in 3 first author publications including two in EMBO Journal. He then moved to the US to work with Bruce Stillman, President of the Cold Spring Harbor Laboratory, while being supported by a Leukaemia and Lymphoma Research Fellowship exploring eukaryotic DNA replication and the role of Cdc6 in initiation of DNA replication. This work resulted in 4 first author publications in Nature Structural & Molecular Biology, PNAS and JBC. Following this period of training he moved to Imperial College London to establish his group in 2006 at MRC-CSC and since 2013 at Imperial College, Institute of Clinical Science. His group reconstituted the loading of the replicative helicase with purified proteins (F1000 – excellent) and identified a series of crucial mechanisms and regulatory principles in DNA replication being published in prominent journals such as Molecular Cell, Nature Structural & Molecular Biology Genes & Development and PNAS.
et al., 2017, Cryo-EM structure of Mcm2-7 double hexamer on DNA suggests a lagging-strand DNA extrusion model, Proceedings of the National Academy of Sciences of the United States of America, Vol:114, ISSN:0027-8424, Pages:E9529-E9538
et al., 2017, From structure to mechanism-understanding initiation of DNA replication, Genes & Development, Vol:31, ISSN:0890-9369, Pages:1073-1088
et al., 2017, Structural basis of Mcm2-7 replicative helicase loading by ORC-Cdc6 and Cdt1, Nature Structural & Molecular Biology, Vol:24, ISSN:1545-9993, Pages:316-+
et al., 2015, Cdc6 ATPase activity disengages Cdc6 from the pre-replicative complex to promote DNA replication, Elife, Vol:4, ISSN:2050-084X
et al., 2015, A reconstituted system reveals how activating and inhibitory interactions control DDK dependent assembly of the eukaryotic replicative helicase, Nucleic Acids Research, Vol:43, ISSN:0305-1048, Pages:10238-10250
et al., 2014, Structural and mechanistic insights into Mcm2-7 double-hexamer assembly and function, Genes & Development, Vol:28, ISSN:0890-9369, Pages:2291-2303
et al., 2014, A unique DNA entry gate serves for regulated loading of the eukaryotic replicative helicase MCM2-7 onto DNA, Genes & Development, Vol:28, ISSN:0890-9369, Pages:1653-1666
Riera A, Tognetti S, Speck C, 2014, Helicase loading: How to build a MCM2-7 double-hexamer, Seminars in Cell & Developmental Biology, Vol:30, ISSN:1084-9521, Pages:104-109
et al., 2013, Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1-MCM2-7 bound to DNA, Nature Structural & Molecular Biology, Vol:20, ISSN:1545-9993, Pages:944-+
et al., 2013, An ORC/Cdc6/MCM2-7 Complex Is Formed in a Multistep Reaction to Serve as a Platform for MCM Double-Hexamer Assembly, Molecular Cell, Vol:50, ISSN:1097-2765, Pages:577-588
et al., 2005, ATPase-dependent cooperative binding of ORC and Cdc6 to origin DNA, Nature Structural & Molecular Biology, Vol:12, ISSN:1545-9985, Pages:965-971
et al., 2009, A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication, Proceedings of the National Academy of Sciences of the United States of America, Vol:106, ISSN:0027-8424, Pages:20240-20245