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User:YosDav/Christian Speck draft-revised

Christian Speck
Born (1970-10-03) 3 October 1970 (age 54)
Berlin, Germany
NationalityGerman, British
Alma materBeuth Hochschule für Technik Berlin (Diplom-Ingenieur, 1995)
Freie Universität Berlin (Diplom, 1997)
Max-Planck-Institute for Molecular Genetics (PhD, 2000)
Known forMCM2-7 helicase loading and activation pathway
Scientific career
FieldsBiochemistry, cryo-EM, epigenetics, high resolution genomics
InstitutionsCold Spring Harbor Laboratory
MRC Clinical Science Centre
Imperial College London
ThesisATP- and ADP-DnaA: New models and mechanisms of dnaA transcription and initiation of DNA replication (2000)
Doctoral advisorWalter Messer
Other academic advisorsBruce Stillman
Websitespecklab.com

Christian Speck (born 3 October 1970) is a German biochemist, biotechnologist and interdisciplinary research scientist in DNA replication. He is Full Professor and Chair of Genome Biochemistry & Molecular Biology and head of the DNA Replication Group in the Faculty of Medicine at the Institute of Clinical Sciences at the Hammersmith Campus of Imperial College London. Speck’s research group studies the mechanisms in genome stability and epigenetics, with a particular interest in disease associated with these processes and the development of novel DNA replication inhibitors for therapeutic purposes.

Education, training and career

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Speck earned his Diplom-Ingenieur degree in Biotechnology in 1995 from Beuth Hochschule für Technik Berlin and his Diplom (1997) and PhD (2000) degrees in Biochemistry from Freie Universität Berlin. For his PhD, he studied bacterial gene regulation and DNA replication[1][2][3][4] as a Max Planck Society PhD Fellow in the laboratory of Walter Messer at the Max Planck Institute for Molecular Genetics in Berlin. In 2001, Speck was awarded a postdoctoral fellowship by the Leukemia & Lymphoma Society to work on the reconstitution and characterisation of the ORC-Cdc6-origin DNA complex in Saccharomyces cerevisiae[5][6] with Bruce Stillman’s group, at Cold Spring Harbor Laboratory. Since 2006, Speck has led the DNA Replication Group, initially at the now defunct Medical Research Council (MRC) Clinical Sciences Centre, and, since 2013, at the Institute of Clinical Sciences at Imperial College London. He was appointed lecturer in 2013, reader in 2015, and Full Professor and Chair of Genome Biochemistry & Molecular Biology in 2016. In 2015, Speck received a Wellcome Trust Investigator Award[7] and was elected Fellow of the Royal Society of Biology (FRSB). He has served on numerous scientific evaluation panels (ANR, DAAD, Horizon 2020) and editorial boards and as the chair of the Athena SWAN opportunities committee, supporting gender equality in research. He is a founding member of the London consortium for cryo-EM (LonCEM)[8][9] and established the cryo-EM facility at the Hammersmith Campus of Imperial College London.

Research

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Speck’s group is focussed on discovering new mechanisms in initiation of DNA replication and understanding the function of replication factors in hetero-chromatin formation. The lab is using an integrative approach involving biochemical, genetic, genomic, structural, and molecular methods to obtain a holistic understanding of the underlying biological processes, uncover novel mechanisms and regulatory principles, and develop specific therapeutic inhibitors for disease associated with these processes.

The group has reconstituted the loading of the eukaryotic replicative helicase onto DNA[10] — an essential step in DNA replication — and has used this system to address the mechanism and regulation of two key events: 1) the stepwise loading of the eukaryotic DNA helicase onto DNA[11][12][13][14][15][16][17][18][19][20], and 2) the kinase-dependent activation of the helicase[17][21][22]. In more recent years, Speck has developed an interest in investigating the role of helicase loading factors in epigenetic memory, which has important implications for human disease and ageing.

References

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  1. ^ Speck, Christian; Weigel, Christoph; Messer, Walter (1997-08-01). "From footprint to toeprint: a close-up of the DnaA box, the binding site for the bacterial initiator protein DnaA". Nucleic Acids Research. 25 (16): 3242–3247. doi:10.1093/nar/25.16.3242. ISSN 0305-1048. PMC 146876. PMID 9297181.{{cite journal}}: CS1 maint: PMC format (link)
  2. ^ Speck, Christian; Weigel, Christoph; Messer, Walter (1999-11-01). "ATP– and ADP–DnaA protein, a molecular switch in gene regulation". The EMBO Journal. 18 (21): 6169–6176. doi:10.1093/emboj/18.21.6169. ISSN 0261-4189. PMC 1171680. PMID 10545126.{{cite journal}}: CS1 maint: PMC format (link)
  3. ^ Speck, Christian. ATP- und ADP-DnaA-Protein: neue Modelle und Mechanismen zur Regulation der dnaA-Transkription und zur Initiation der DNA-Replikation (Thesis).
  4. ^ Speck, Christian; Messer, Walter (2001-03-15). "Mechanism of origin unwinding: sequential binding of DnaA to double- and single-stranded DNA". The EMBO Journal. 20 (6): 1469–1476. doi:10.1093/emboj/20.6.1469. ISSN 0261-4189. PMC 145534. PMID 11250912.{{cite journal}}: CS1 maint: PMC format (link)
  5. ^ Speck, Christian; Chen, Zhiqiang; Li, Huilin; Stillman, Bruce (2005-11). "ATPase-dependent cooperative binding of ORC and Cdc6 to origin DNA". Nature Structural & Molecular Biology. 12 (11): 965–971. doi:10.1038/nsmb1002. ISSN 1545-9985. PMC 2952294. PMID 16228006. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  6. ^ Speck, Christian; Stillman, Bruce (2007-04). "Cdc6 ATPase Activity Regulates ORC·Cdc6 Stability and the Selection of Specific DNA Sequences as Origins of DNA Replication". Journal of Biological Chemistry. 282 (16): 11705–11714. doi:10.1074/jbc.m700399200. ISSN 0021-9258. PMC 3033201. PMID 17314092. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  7. ^ "Research to unzip secrets of our DNA wins Wellcome Trust award". LMS London Institute of Medical Sciences. 2015-07-27. Retrieved 2021-08-27.
  8. ^ "A London consortium to establish a high resolution cryo-electron microscopy facility for research and training (360G-Wellcome-206175_Z_17_Z)".{{cite web}}: CS1 maint: url-status (link)
  9. ^ "Imperial to lead new £3m London consortium for structural biology | Imperial News | Imperial College London". Imperial News. Retrieved 2021-08-27.
  10. ^ Evrin, Cecile; Clarke, Pippa; Zech, Juergen; Lurz, Rudi; Sun, Jingchuan; Uhle, Stefan; Li, Huilin; Stillman, Bruce; Speck, Christian (2009-12-01). "A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication". Proceedings of the National Academy of Sciences. 106 (48): 20240–20245. doi:10.1073/pnas.0911500106. PMC 2787165. PMID 19910535.{{cite journal}}: CS1 maint: PMC format (link)
  11. ^ Evrin, Cecile; Fernández-Cid, Alejandra; Zech, Juergen; Herrera, M. Carmen; Riera, Alberto; Clarke, Pippa; Brill, Shlomo; Lurz, Rudi; Speck, Christian (2013-03-01). "In the absence of ATPase activity, pre-RC formation is blocked prior to MCM2–7 hexamer dimerization". Nucleic Acids Research. 41 (5): 3162–3172. doi:10.1093/nar/gkt043. ISSN 0305-1048. PMC 3597701. PMID 23376927.{{cite journal}}: CS1 maint: PMC format (link)
  12. ^ Fernández-Cid, Alejandra; Riera, Alberto; Tognetti, Silvia; Herrera, M. Carmen; Samel, Stefan; Evrin, Cecile; Winkler, Christian; Gardenal, Emanuela; Uhle, Stefan; Speck, Christian (2013-05). "An ORC/Cdc6/MCM2-7 Complex Is Formed in a Multistep Reaction to Serve as a Platform for MCM Double-Hexamer Assembly". Molecular Cell. 50 (4): 577–588. doi:10.1016/j.molcel.2013.03.026. ISSN 1097-2765. {{cite journal}}: Check date values in: |date= (help)
  13. ^ Sun, Jingchuan; Evrin, Cecile; Samel, Stefan A.; Fernández-Cid, Alejandra; Riera, Alberto; Kawakami, Hironori; Stillman, Bruce; Speck, Christian; Li, Huilin (2013-08). "Cryo-EM structure of a helicase loading intermediate containing ORC–Cdc6–Cdt1–MCM2-7 bound to DNA". Nature Structural & Molecular Biology. 20 (8): 944–951. doi:10.1038/nsmb.2629. ISSN 1545-9985. PMC 3735830. PMID 23851460. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  14. ^ Evrin, Cecile; Fernández-Cid, Alejandra; Riera, Alberto; Zech, Juergen; Clarke, Pippa; Herrera, M. Carmen; Tognetti, Silvia; Lurz, Rudi; Speck, Christian (2014-02-01). "The ORC/Cdc6/MCM2-7 complex facilitates MCM2-7 dimerization during prereplicative complex formation". Nucleic Acids Research. 42 (4): 2257–2269. doi:10.1093/nar/gkt1148. ISSN 0305-1048. PMC 3936773. PMID 24234446.{{cite journal}}: CS1 maint: PMC format (link)
  15. ^ Samel, Stefan A.; Fernández-Cid, Alejandra; Sun, Jingchuan; Riera, Alberto; Tognetti, Silvia; Herrera, M. Carmen; Li, Huilin; Speck, Christian (2014-08-01). "A unique DNA entry gate serves for regulated loading of the eukaryotic replicative helicase MCM2–7 onto DNA". Genes & Development. 28 (15): 1653–1666. doi:10.1101/gad.242404.114. ISSN 0890-9369. PMC 4117941. PMID 25085418.{{cite journal}}: CS1 maint: PMC format (link)
  16. ^ Chang, FuJung; Riera, Alberto; Evrin, Cecile; Sun, Jingchuan; Li, Huilin; Speck, Christian; Weinreich, Michael (2015-08-25). Walter, Johannes (ed.). "Cdc6 ATPase activity disengages Cdc6 from the pre-replicative complex to promote DNA replication". eLife. 4: e05795. doi:10.7554/eLife.05795. ISSN 2050-084X. PMC 4547096. PMID 26305410.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  17. ^ a b Cite error: The named reference :0 was invoked but never defined (see the help page).
  18. ^ Riera, Alberto; Barbon, Marta; Noguchi, Yasunori; Reuter, L. Maximilian; Schneider, Sarah; Speck, Christian (2017-06-01). "From structure to mechanism—understanding initiation of DNA replication". Genes & Development. 31 (11): 1073–1088. doi:10.1101/gad.298232.117. ISSN 0890-9369. PMC 5538431. PMID 28717046.{{cite journal}}: CS1 maint: PMC format (link)
  19. ^ Yuan, Zuanning; Riera, Alberto; Bai, Lin; Sun, Jingchuan; Nandi, Saikat; Spanos, Christos; Chen, Zhuo Angel; Barbon, Marta; Rappsilber, Juri; Stillman, Bruce; Speck, Christian (2017-03). "Structural basis of Mcm2–7 replicative helicase loading by ORC–Cdc6 and Cdt1". Nature Structural & Molecular Biology. 24 (3): 316–324. doi:10.1038/nsmb.3372. ISSN 1545-9985. PMC 5503505. PMID 28191893. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  20. ^ Yuan, Zuanning; Schneider, Sarah; Dodd, Thomas; Riera, Alberto; Bai, Lin; Yan, Chunli; Barbon, Marta; Magdalou, Indiana; Ivanov, Ivaylo; Stillman, Bruce; Li, Huilin (2020-07-28). "Structural mechanism of helicase loading onto replication origin DNA by ORC-Cdc6". Proceedings of the National Academy of Sciences. 117 (30): 17747–17756. doi:10.1073/pnas.2006231117. PMC 7395460. PMID 32669428.{{cite journal}}: CS1 maint: PMC format (link)
  21. ^ Sun, Jingchuan; Fernandez-Cid, Alejandra; Riera, Alberto; Tognetti, Silvia; Yuan, Zuanning; Stillman, Bruce; Speck, Christian; Li, Huilin (2014-10-15). "Structural and mechanistic insights into Mcm2–7 double-hexamer assembly and function". Genes & Development. 28 (20): 2291–2303. doi:10.1101/gad.242313.114. ISSN 0890-9369. PMC 4201289. PMID 25319829.{{cite journal}}: CS1 maint: PMC format (link)
  22. ^ Herrera, M. Carmen; Tognetti, Silvia; Riera, Alberto; Zech, Juergen; Clarke, Pippa; Fernández-Cid, Alejandra; Speck, Christian (2015-12-02). "A reconstituted system reveals how activating and inhibitory interactions control DDK dependent assembly of the eukaryotic replicative helicase". Nucleic Acids Research. 43 (21): 10238–10250. doi:10.1093/nar/gkv881. ISSN 0305-1048. PMC 4666391. PMID 26338774.{{cite journal}}: CS1 maint: PMC format (link)
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