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Martin Seizl
Cramer Lab
Gene Center, Feodor-Lynen-Str. 25, 81377 Munich
089 2180 76958
089 2180 76999

Structure-Function Analysis of the Transcription Coactivator Complex Mediator

Transcription is the fundamental biological process of synthesizing RNA from a DNA template by RNA polymerase. In eukaryotes regulation of RNA polymerase II (Pol II) transcription represents the basis for fundamental biological phenomena, including cell differentiation, organism development and biodiversity. It occurs at various stages including transcription initiation, mRNA processing, mRNA export, mRNA turnover, translation and protein turnover. However the regulation of transcription initiation is the crucial step involving hundreds of activator and repressor proteins. Coactivator complexes are necessary to integrate multiple regulatory signals and transmit an integrated output to Pol II.

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The most prominent coactivator is the multi-protein complex Mediator, which constitutes the central interface between regulatory proteins and Pol II. It is required for regulated transcription on most if not all yeast genes and is conserved throughout eukaryotes. The Mediator complex from the yeast Saccharomyces cerevisiae consists of 25 subunits of which 22 have homologs in higher eukaryotes, comprising a total molecular weight of around 1.5 MDa. Based on observations from electron microscopy and biochemical studies the Mediator complex can be subdivided into four modules referred to as Head, Middle, Tail and Kinase module. Despite its fundamental role in gene regulation, the molecular mechanisms underlying its function are poorly understood.

To elucidate the mechanism, I will obtain more structural information on the Mediator and correlate the observed structural interactions with functional roles in vitro and in vivo. To achieve this goal I will apply a wide range of methods from X-ray crystallography to in vitro transcription and yeast genetics.

  • PostDoc (since 2011)
    LMU Munich - P. Cramer lab
  • Visiting Scientist (08/2011 - 09/2011)
    University of Victoria, Victoria, Canada
  • PhD student (2007 - 2011)
    LMU Munich - P. Cramer lab
    Thesis: The Mediator Head module and regulation of RNA polymerase II transcription initiation

  • Biochemistry - M.Sc. (2005 - 2007)
    LMU Munich & Fred Hutchinson Cancer Research Center Seattle
    Thesis: Structural and functional studies of the Mediator head module
  • Internship - Crelux GmbH (2005)
    Structural Biology of a protein kinase

  • Human Nutrition - B.Sc. (2001 - 2005)
    TU Munich & Oklahoma State University
    Thesis: Degradation of PrP-res by proteases of coryneform bacteria
  • Larivière L, Seizl M, Cramer P. A structural perspective on Mediator function. Current opinion in cell biology. Epub 2012 Feb 15
  • Seizl M1, Hartmann H1, Hoeg F1, Kurth F, Martin DE, Söding J, Cramer P.
  • Member of the ENB Graduate Program "Protein Dynamics in Health and Disease"(2008 - 2011)
  • Boehringer-Ingelheim PhD fellowship for basic biomedical research (2007 - 2010)
  • Roemer prize for young scientists (2007)
  • EMBO short term fellowship (2006)
  • Organizer of the several ENB softskill workshops


Postdoc
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Martin Seizl
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Alumni
Biochemistry
Cramer Lab