CV Science

Patrick SCHULTZ PhD molecular biology

Course and current status

Qualifications:

Head of the Integrated Structural Biology department at IGBMC, Illkirch, France, 2007-2018

Research director (CNRS, DR1) at IGBMC, Illkirch, France, since 2005.

Director of a research unit of 12 teams in integrative cryo electron microscopy (GDR 2368) (2004-2008)

Research director (CNRS, DR2) at the IGBMC, Illkirch, France (1999-2005)

Assistant professor at the LGME (CNRS, CR1), Strasbourg, France (1991-1999)

Ph.D. in Molecular Biology (1985) Laboratoire de Génétique Moléculaire des Eucaryotes (LGME), Strasbourg, France

Positions and Employment:

Head of the Integrated Structural Biology Department of the IGBMC, since 2007

Team Leader at IGBMC, Illkirch, since 2000

Research assistant at the LGME, Strasbourg (1990- 2000)

Foundation for Medical Research Fellowship at the LGME, Strasbourg (1989-1990)

Research ministry fellowship at the LGME, Strasbourg with P. Oudet (1987-1989)

Fellowship at the EMBL, Heidelberg, with J. Dubochet (1985-1987)

Ph.D. work at the LGME, Strasbourg under the supervision of P. Oudet (1983-1987)

Scientific summary

My major scientific interest is to understand the structure-function relationships of multi-protein complexes involved in transcription regulation, DNA repair, and in the modulation of chromatin structure. In my team we use a combination of biochemistry, yeast genetics, molecular biology and structural biology methods in particular high resolution cryo-EM the implementation of which I pioneered in Strasbourg University in the early 90’. We obtained structural and functional insights into the transcription/DNA repair factor TFIIH and provided the first structural structural models of the general transcription factor TFIID from yeast by working out subunit maps of the complexes. In collaboration with I. Berger (EMBL, Grenoble) we determined a 10 Å resolution structure of a recombinant human core-TFIID subcomplex consisting of a subset of 5 subunits and showing two-fold symmetry (Bieniossek et al., Nature, 2013). We demonstrated that binding of the TAF8/TAF10 heterodimer breaks the original symmetry of core-TFIID and analyzed the incorporation of TAF2 into core-TFIID (Trowitzsch et al., Nature Commun, 2015). We published the first near atomic model of yeast TFIID bound to a gene promoter (Kolesnikova et al., Nature Commun, 2018). We could position existing subunit atomic structures, propose a model for the subunit organization of TFIID, and identify two promoter DNA interaction domains separated by 35 bp. This work provided new insights into the way TFIID recognizes and binds to gene promoters. We determined the first model of SAGA revealing the modular organization of the complex into functional modules (Wu et al., Mol. Cell, 2004, Durand et al., structure, 2014). We positioned the histone acetyl transferase (HAT) module and showed that it is located in a flexible arm of SAGA. We determined the first cryo-EM model of SAGA and revealed the structural organization of Tra1 at 5.7 Å resolution (Sharov et al., Nature Commu. 2017). At this resolution, we could trace the main chain of the 430 KDa Tra1 protein, which is key to signal cellular events to the transcription machinery. Recently we determined an atomic model of SAGA (Papai et al., 2020) showing that SAGA and TFIID share a similar TBP-delivery machine composed of a deformed octamer of histone fold containing proteins. We show how TBP is sterically hindered to bind DNA, an inhibition released by TFIIA. This structure showing at atomic details the mode of interaction of TBP with SAGA was cited in several reviews and was awarded the Grandes Avancées Françaises en Biologie distinction by the French academy of sciences. 

Major scientific contributions

• Atomic structure of SAGA bound to TBP (Papai et al., 2020, Nature, 577, 711-716)
• Atomic structure of core TFIID bound to its promoter element (Kolesnikova et al., 2018, Nature comm. 9, 4666)
• Structure of an initiation competant RNA polymerase I complex at sub nanometric resolution in which secondary structural elements are revealed. (Pilsl et al., 2016, Nature comm 7: 12129)
• Struture of  a TFIID core complex at 10 Å resolution (Bieniossek et al., 2013, Nature. 493:699-702.)
• First structural model of the SAGA coactivator Wu et al., 2004, Mol. Cell. 15, 199-208.
• Location of the DeUbiquitination module within the SAGA coactivator (Durand et al., 2014, Structure 22, 1553-1559)
• Role of TFIID in activated transcription (Papai et al., 2010 Nature 465:956-60).
• Structural model of the complex between HIV-1 integrase and the human cofactor LEDGF (Michel et al., 2009. EMBO J 28(7), 980-991).
• Mapping Functional sites within yeast TFIID general transcription factor (Leurent, et al., 2004, EMBO J. 23 : 719-27.
• First structural model of the human general transcription factor TFIIH (Schultz et al., 2000, Cell, 102, 599-607.