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Alexander Wolf: Molecular Toxicology and Pharmacology

alexander.wolf@helmholtz-muenchen.de
www.helmholtz-muenchen.de/en/toxi/research/research-fields-research-units/epigenetics/research/index.html
Address
Institute of Molecular Toxicology & Pharmacology, Helmholtz Zentrum Munich, Ingolstaedter Landstr. 1, 85764 Neuherberg
Germany
Keywords

RNA modifications, RNA processing, Fe(II) & 2-oxoglutarate dependent oxygenases, hydroxylation, hypoxia

Models

mammalian cell culture

Techniques

Fluorescence microscopy, confocal laser scanning microscopy, high content imaging; immunoprecipitation coupled to mass spectrometry (proteomics); recombinant protein purification; several assays (in cells, in vitro) for analyses of protein-protein/protein-peptide/protein-nucleic acid interaction

Collaborations outside COST

Short description of ongoing research projects

We are interested in the basic mechanisms of epigenetic regulation via modifications on proteins or RNA. The overall pattern of modifications can vary due to external stimuli. Dysfunction of this regulatory network can cause severe defects, like cancer or diabetes. Our work focuses on a large enzyme superfamily, which is present in eukaryotes and prokaryotes: the Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases. In order to shed further light on the role of 2OG oxygenases in regulating gene expression we use a combination of in vivo and in vitro techniques, including cell based work, microscopy and proteomics, as well as recombinant enzyme purification and characterization.

Publications
  1. Böttger A, Islam MS, Chowdhury R, Schofield CJ, Wolf A. The oxygenase Jmjd6 - a case study in conflicting assignments. Biochem J. 2015 Jun 1;468(2):191-202.
  2. Loenarz C, Sekirnik R,Thalhammer A, Ge W, Spivakovsky E, Mackeen MM, McDonough MA, Cockman ME, Kessler BM, Ratcliffe PJ, Wolf A, Schofield CJ. Hydroxylation of the eukaryotic ribosomal decoding centre affects translational accuracy. Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):4019-24.
  3. Ge W*, Wolf A*, Feng T, Ho C, Sekirnik R, Zayer A, Granatino N, Cockman ME, Loenarz C, Loik ND, Hardy AP, Claridge TDW, Hamed RB, Chowdhury R, Gong L, Trudgian DC, Jiang M, Mackeen MM, McCullagh JS, Gordiyenko Y, Thalhammer A, Yamamoto A, Yang M, Liu Y, Zhang Z, Schmidt-Zachmann M, Kessler BM, Ratcliffe PJ, Preston GM, Coleman ML, Schofield CJ. Oxygenase Catalysed Ribosome Hydroxylation is Conserved From Prokaryotes to Humans. Nature Chem Biol. 2012, 3, 960-962.
  4. Webby CJ*, Wolf A*, Gromak N*, Dreger M, Kramer H, Kessler B, Nielsen ML, Schmitz C, Butler DS, Yates JR 3rd, Delahunty CM, Hahn P, Lengeling A, Mann M, Proudfoot NJ, Schofield CJ, Böttger A. Jmjd6 catalyses lysyl-hydroxylation of U2AF65, a protein associated with RNA splicing. Science. 2009 Jul 3;325(5936):90-3.
Other activities of potential interest to others


Cost UE