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: firstname.lastname@example.org
NEW PHD POSITION AVAILABLE
A 3.5-year PhD position is available in the Speck lab - the starting date is October 2021.
The student will use and develop a novel single-molecule biophysical method (mass-photometry) to investigate a key step in DNA replication, the loading of the replicative helicase on DNA, and explore this multi-step reaction in a time resolved manner. This work will address how DNA replication works and contribute to the development of helicase loading inhibitors as a potential anti-cancer therapy.
The project is a collaboration between Refeyn Ltd and the Imperial College London research groups of Professor Speck and Professor Rueda. Refeyn, a company based in Oxford, has recently developed and brought to market a breakthrough technology that measures the molecular weight of individual proteins and protein complexes by mass photometry. This revolutionary biophysical technique is highly-accurate, very fast, label-free and allows the use of native proteins.
The group of Professor Speck, including 7 postdocs, 3 PhD students and 2 technicians, applies a range of biochemical, structural, proteomic and genetic/genomic approaches in order to investigate DNA replication and chromatin structure. We work in a highly collaborative way and provide PhD students with a multidisciplinary learning environment. Applicants that have interest in genome stability, method development and a very good background in biochemistry or biophysics are strongly encouraged to apply.
A project description and application instructions can be found here.
Interested candidates can contact Professor Speck directly via email (email@example.com)
Major scientific accomplishmenTs
- Structural mechanism of helicase loading onto replication origin DNA by ORC-Cdc6 (Proceedings of the National Academy of Science of the United States of America, 2020)
- The cryo-EM structure of Mcm2-7 on DNA suggests a new lagging-strand DNA extrusion model (Proceedings of the National Academy of Science of the United States of America, 2017)
- Structural basis of MCM2-7 replicative helicase loading by ORC-Cdc6 and Cdt1 (Nature Structure & Molecular Biology, 2017)
- 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), Imperial College, Wellcome Trust, Leukemia & Lymphoma Society, Max Planck Society, and MRC.
Group News & Congratulations to …
Great News, our iCASE studentship application was successful. We are recruiting a PhD student for October 2021 to work on a collaborative project with Refeyn Ltd and Professor Rueda to investigate DNA replication by mass photometry and to develop new analysis approaches. Interested candidates please contact Christian@ firstname.lastname@example.org
The project description can be found here:
Lepakshi Ranjha and Marina Ivanova join the lab as Postdocs. Big welcome!
We say good bye to the fantastic Sarah Schneider, who will embark on her new career as the cryo-EM facility manager at EMBL Grenoble. We will miss you wish you all the best for the future.
Work in the lab is slowly starting again...
With Covid-19, lab meetings, journal clubs and 1:1 meetings move to an online platform.
Recruitment during Covid-19. Two fantastic postdocs will be joining in October - could not have hoped for a better outcome.
We had in February our group's third retreat at the beautiful Bellropes country estate. Exploration of scientific concepts, games and model building, lots of cooking and a visit of a brewery.
Great news, our BBSRC grant application was successful! Huge congratulations to Sarah S, Al and Yasunori for writing a fantastic proposal and achieving a superb ranking: 4th out of 89.
Our first data collection on the new LonCEM Titan Krios microscope using the K3 in super-resolution mode has just started. A dream come true...
Jessica Ellins and Shenaz Allyjaun join the lab as PhD students. Big welcome!
Joseph Dobbs joins the Group as a BSc student. Big welcome!
Greta Baltusyte joins the Group as a BA student. Big welcome!
Halil Bounoua joins the lab to carry out his BSc research project. Big welcome!
Sarah Faull joins the lab as a Postdoc. Big welcome!
Jillian Tay joins the lab to carry out her MRes research project. Big welcome!
Our eight GPU Cluster is almost ready for action - can't wait to see it happen...
Megan Turner joins the lab to carry out her MSc research project. Big welcome!
Audrey Mossler joins the group to gain experience in a UK lab. Big welcome!
Adrian Soderholm joins the lab to carry out his MRes research project. Big welcome!
Almutasem Saleh joins the lab as a Postdoc. Big welcome!
Marta, for passing her viva with minor corrections. Thanks to the examiners: Aga Gambus and Dave Carling.
Tomorrow the lab goes on a retreat to Southminster. 3-days of fun, exploring of ideas & concepts, collaborative cooking and baking. Can't wait...
Adrian Soderholm joins the Group as a MRes student. Big welcome!
Cecilia Pennica joins the lab as a Postdoc. Big welcome!
I have never spend so much money on hard disks. Today our new 50TB storage server went online.
Marta for submitting her thesis. Well done!
Our new neighbour arrived - welcome to Kyle Morris, Senior Scientist, advancing the cryo-EM efforts at the institute.
Owen Burbidge joins the lab as a Senior Biochemical Research Scientist. Big welcome!
Vera Leber joins the lab as a Postdoc. Big welcome!
Our new BBSRC grant was funded! Congratulations to everybody who helped, in particular Sarah.
Marta for having successfully applied for a Biochemical Society Sponsored Events Grant to support the Biochemistry Club.
Sarah for being awarded a prestigious two year year Deutsche Forschungsgemeinschaft (DFG) Research Fellowship
Ricardo Aramayo joined the institute as a senior cryo-EM scientist. He will take care of the cryo-EM facility. Big welcome!
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.
The Imperial College PhD Presidents Scholarship and the MRC DTP studentship for October 2019 have been filled now. New fully funded PhD studentships will be advertised when they become available. Candidates that want to apply for scholarships can continue to contact Christian Speck by email (email@example.com). Please indicate in your email for which fellowship you are eligible to apply. Please keep in mind that the Imperial College PhD Presidents Scholarship has been filled and therefore is not available.
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 (firstname.lastname@example.org) 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 (email@example.com); 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 (firstname.lastname@example.org) 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, JSPS and MRC awarded to members of our lab.
The SPECK LAB
About Prof. 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-2016/2017- LIF, DAAD and the French National Research Agency - ANR. He sits on the editorial board of the Biochemical Journal, chairs the Institutes Athena Swan committee and sits on the Clinical Science Centre Postgraduate Education Committee. 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, Prof. 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 London to establish his group in 2006 at MRC-CSC and since 2013 at Imperial College London, 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. In 2017 he became one of the founding members of the Wellcome Trust funded LonCEM consortium, which was awarded a Titan Krios cryo-EM with K3 detector. In the same year, he became a member of the Imperial College London Centre for Structural Biology (CSB) and in 2018 member of the associated Block Allocation Group (BAG) for flexible access to the Krios 1-4 of eBIC (Diamond Light Source - Harwell). In 2017 Christian, while being supported by Sarah S, has set-up the local cryo-EM screening facility at the Institute of Clinical Sciences. The facility is by now is fully operational and supports the electron microscopy efforts of the whole institute.
et al., 2019, An integrated workflow for crosslinking mass spectrometry., Mol Syst Biol, Vol:15
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:1549-5477, 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:316-324
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:1362-4962, Pages:10238-10250
Speck C, 2015, Cdc6 ATPase activity disengages Cdc6 from the pre-replicative complex to promote DNA replication, Elife, Vol:4, ISSN:2050-084X
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 Structure Molecular Biology
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., 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
et al., 2005, ATPase-dependent cooperative binding of ORC and Cdc6 to origin DNA., Nature Structural & Molecular Biology, Vol:12, ISSN:1545-9993, Pages:965-971