SciLifeLab The Svedberg seminar series, Thomas Carell, Epigenetics


Monday March 6th

Thomas Carell

Center for Integrative Protein Science, Department of Chemistry, Ludwig Maximilians University, Munich, Germany

Thomas Carell (Ph. D) was raised in Bad-Salzuflen (Germany). He studied chemistry at the Universities of Münster and Heidelberg. In 1993 he obtained his doctorate with Prof. H. A. Staab at the Max Planck Institute of Medical Research in Heidelberg. After postdoctoral training with Prof. J. Rebek at MIT (Cambridge, USA) in 1993-1995, Thomas Carell moved to the ETH Zürich (Switzerland) as an ass. professor to start independent research. He obtained his habilitation (tenure) in 2000. He subsequently accepted a full professor position for Organic Chemistry at the Philipps-Universität in Marburg (Germany). In 2004 Thomas Carell moved to the Ludwig-Maximilians-Universität (LMU) in Munich (Germany), where he is heading a research group in chemical biology focused to analyze the chemistry of epigenetic programming in DNA and RNA. Thomas Carell is a member of the National German Academy Leopoldina and of the Berlin-Brandenburgische Academy of Arts and Sciences. He is a recipient of the Cross of Merit from the Federal Republic of Germany. Thomas Carell obtained the German Leibniz award in 2014 (comparable to a HHMI investigator in the USA).

DNA Bases beyond Watson and Crick

Epigenetic information is stored in the form of modified bases in the genome. The positions and the kind of the base modifications determines the identity of the corresponding cell. Setting and erasing of epigenetic imprints controls the complete development process starting from an omnipotent stem cells and ending with an adult specialized cell. I am going to discuss the latest results related to the function and distribution of the epigenetic marker bases 5-hydroxymethylcytosine (hmC), 5-formylcytosine (fC), 5-carboxycytosine (caC) and 5-hydroxymethyluracil (Scheme 1).[1] These nucleobases control epigenetic programming of stem cells and some of these bases are also detected at relatively high levels in brain tissues. Synthetic routes to these new bases will be discussed that enable today preparation of oligonucleotides containing the new bases. The second part of the lecture will cover mass spectroscopic approaches to decipher the biological functions of the new epigenetic bases of which some were described in the past as pure DNA lesions.[2] In particular, results from quantitative mass spectrometry, new covalent-capture proteomics mass spectrometry and isotope tracing techniques will be reported. The data allow us to unravel the chemistry in stem cells and the protein networks that are controlled by the epigenetic base modifications.[3] Finally I am dicussing potential präbiotic origins of these modfied bases[4].

[1]   M. Wagner, J. Steinbacher, T. F. Kraus, S. Michalakis, B. Hackner, T. Pfaffeneder, A. Perera, M. Müller, A. Giese, H. A. Kretzschmar, T. Carell Angew. Chem. Int. Ed. 2015, doi: 10.1002/anie.201502722. Age-Dependent Levels of 5-Methyl-, 5-Hydroxymethyl-, and 5-Formylcytosine in Human and Mouse Brain Tissues.

[2]   Perera, D. Eisen, M. Wagner, S. K. Laube, A. F. Künzel, S. Koch, J. Steinbacher, E. Schulze, V. Splith, N. Mittermeier, M. Müller, M. Biel, T. Carell, S. Michalakis Cell Rep. 2015 , 11, 1-12. TET3 Is Recruited by REST for Context-Specific Hydroxymethylation and Induction of Gene Expression

[3]   C.G. Spruijt, F. Gnerlich, A.H. Smits, T. Pfaffeneder, P.W.T.C. Jansen, C. Bauer, M. Münzel, M. Wagner, M. Müller, F. Khan, H.C. Eberl, A. Mensinga, A.B. Brinkman, K. Lephikov, U. Müller, J. Walter, R. Boelens, H. van Ingen, H. Leonhardt, T. Carell, M. Vermeulen Cell. 2013, 152, 1146-59. Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives

[4]   S. Becker, I. Thoma, A. Deutsch, T. Gehrke, P. Mayer, H. Zipse, T. Carell, Science, 2016, 352 (6287), 833-836.
A high-yielding, strictly regioselective prebiotic purine nucleoside formation pathway.

 

Read more about Thomas Carell’s research

 

Host: Daniel Globisch