ABOUT

since 2009
RNS Berlin UG (haftungsbeschränkt), formerly Research Network Services Ltd., Berlin
Director and sole Shareholder
main activities: scientific visualisation and animation (since 2019), research project management (since 2009), including:

EURATRANS Project Manager (2010 to 2015)
European large-scale functional genomics in the rat for translational research (EURATRANS), FP7 Large-scale integrated research project, coordinator: Norbert Hübner, MDC Berlin

BiomarCaRE Project Manager (2011 to 2016)
Biomarker for Cardiovascular Risk Assessment across Europe (BiomarCaRE), FP7 Large-scale integrated research project, coordinators: Stefan Blankenberg and Tanja Zeller, UKE Hamburg

2016 to 2019
Design Akademie Berlin
Bachelor of Arts (B.A.), study Film and Motion Design

2015 to 2016
Akademie für Illustration und Design (AID) , Berlin
Vorstudienjahr Design

2006 - 2010
Medical Research Council (MRC) Clinical Sciences Centre(CSC) (now MRC London Institute of Medical Sciences), London, United Kingdom
EURATools Project Manager
European Rat Tools for Functional Genomics (EURATools), FP6 Integrated Project; Co-ordinator: Tim Aitman, MRC Clinical Sciences Centre, London (now: University of Edinburgh)

1997 to 2006
Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany
2004 to 2006: Research Grants, Groupleader Extramural Funding
2002 to 2003: Support of the proposal processes for projects within the 6th European Framework Programme
1997 to 2002: Ph.D. thesis in the Heinemann Lab (see other tab)
1997 to 2002: Associated membership in the Graduate College "Model Studies of Structures, Properties and Recognition of Biological Macromolecules" (Speaker: Prof. Dr. Wolfgang Höhne, Charité Berlin), Co-organisation of the year 2000 meeting "Berlin Humboldt School on Structural Biology".

1991 to 1997
Johannes Gutenberg Universität Mainz, Germany
1996/97: Diploma thesis under the supervision of Prof. Bernd Kaina (toxicology) and Prof. Horst Kunz (organic chemistry).
1991 to 1996: Study chemistry (Diploma)

1994 to 1995
University of California, Irvine, CA
DAAD-scholarship, laboratory work in the groups of Prof. Harald Biessmann and Prof. Donald F.Senear (biochemistry, molecular biology)

1990 to 1991
University Hospital of the Johannes Gutenberg University Mainz, Germany
Civilian Service in the 1. Medical Clinic (clinical director Prof. H.H. Meyer zum Büschenfelde)

1981 to 1990
Kant-Gymnasium, Boppard, Germany
Abitur

Journals

Erik Werner (2022): Strategies for the Production of Molecular Animations. Frontiers in Bioinformatics (2), article 793914.
DOI: 10.3389/fbinf.2022.793914.

Erik Werner, Wolfgang Wende, Alfred Pingoud, Udo Heinemann (2002): High resolution crystal structure of domain I of the S. cerevisiae Homing Endonuklease PI-SceI.
Nucleic Acids Research30(18), 3962 - 3971

      : 1GPP


Erik Werner, Mathias Ziegler, Felicitas Lerner, Manfred Schweiger, Udo Heinemann (2002): Crystal structure of human nicotinamide mononucleotide adenylyltransferase in complex with NMN.
FEBS Lett.516, 239-244
Corrigendum: FEBS Lett.523, 254-255
      : 1GZU


Erik Werner, Mathias Ziegler, Felicitas Lerner, Manfred Schweiger, Yves A. Muller, Udo Heinemann (2002): Crystallization and preliminary X-ray analysis of human nicotinamide mononucleotide adenylyltransferase (NMNAT).
Acta Crystallogr.D58, 140-142



Perini, L.T., Doherty, E.A., Werner, E. , Senear, D.F. (1996): Multiple specific CytR binding sites at the Escherichia coli deoP2 promoter mediate both cooperative and competitive interactions between CytR and cAMP receptor protein.
J. Biol. Chem.271,33242-55
   

Theses

B.A. Thesis (2019)

Science vs. Design - Principle strategies for the production of molecular animations

Short Abstract
The author of this thesis and owner of the company RNS Berlin UG offers scientific animation and motion design to scientists to empower their scientific communicating and ultimately create more knowledge. This thesis determines the strategic brand positioning of RNS Berlin UG. To enable this effort, the principle strategies for the production of molecular animations are determined. Design principles are deemed universally applicable to any design process with the major exception of the so-called Disney animation principles. They mimic natural movement from every day life experience that has no equivalent in the atomic, nano-scale world.
A set of principle strategies for the production of molecular animations is determined with the Principle of Consistent Complexity in the center. It requests the complexity level of a molecular animation to be consistent throughout, including the representation detail level, the associated motion and the main character - environment relation. Ultimate determinant of the overall complexity is the communication goal target. Also, the expertise level of the target audience may restrict the maximum complexity level but the animation should go beyond and educate the audience further. The animation may include data from various resources, but also predictions, assumptions or even speculations. The level of speculation should be visualised in the animation and the use of artistic license is to be reduced to a minimum. Transparency for the sake of authenticity and credibility is key. Finally, methods of cinematic storytelling should be used tell the molecular story. A tool visualising the development of the complexity is predicted to reveal patterns of animation and storytelling types.

Ph.D. Thesis (2002)

Two Ways of Binding Nucleotides
Crystal Structures of Nicotinamide Mononucleotide Adenylyltransferase from Homo sapiens and of Domain I of the Homing Endonuclease PI-SceI from Saccharomyces cerevisiae

more details on the next tab

Diploma Thesis (1997)

Nachweis von DNA-Addukten durch Hochleistungs-Flüssigkeits-Chromatographie (HPLC) und dessen Anwendung auf die DNA-Reparatur

Abstract (German only)
Die vorliegende Arbeit hatte zum Ziel, DNA-Schäden (die Methylpurine 7-Methyl-guanin, O6-Methylguanin und 3-Methyladenin sowie den oxidativen DNA-Schaden 8-Hydroxyguanin) durch Hochleistungs-Flüssigkeits-Chromatographie (HPLC) nachzuweisen.
Die Methylpurine wurden als Nucleobasen unter isokratischen Chromatographie-bedingungen durch eine stark saure Ionenaustauschersäule getrennt und entweder durch elektrochemische Detektion oder radioaktive Markierung nachgewiesen. Dabei erwies sich die radioaktive Markierung um den Faktor 102 bis 103 empfindlicher als die elektrochemische Detektion; gegenüber der UV-Absorptionsmessung war die radioaktive Markierung sogar um den Faktor 105 bis 106 empfindlicher. Das entwickelte System wurde verwendet, um die Reparatur der Methylpurine in Zellen des Chinesischen Hamsters und in Mausfibroblasten, die entweder mit N-Methyl-N-nitrosoharnstoff (MNU) oder N-Methyl-N'-nitro-N-nitrosoguanidin (MNNG) behandelt worden waren, zu untersuchen. Die Purine wurden durch saure Hydrolyse aus der DNA freigesetzt.
Es wurden die Zellinien CHO-9 und TK47-AT17-C3 hinsichtlich ihrer Reparaturfähigkeit verglichen. Die beiden Zellinien unterscheiden sich darin, daß die TK47-AT17-C3-Zellen die O6-Methylguanin-DNA-Methyltransferase (MGMT) exprimieren, während in CHO-9-Zellen dies nicht erfolgt. Übereinstimmend damit zeigen TK47-AT17-C3-Zellen eine Reparatur von O6-Methylguanin.
Weiterhin wurden Mausfibroblasten der Zellinien BK4 Wildtyp (WT), BK4 fos-/- und BK1 p53-/- hinsichtlich ihrer Reparaturfähigkeit verglichen. Sie unterscheiden sich in der Expression der Transkriptionsfaktoren Fos bzw. p53. Während in BK4 WT-Zellen beide Faktoren exprimiert werden, sind BK4 fos(-/-)-Zellen defizient für Fos und BK1 (p53-/-)-Zellen für p53. Das Fehlen der Transkriptionsfaktoren Fos und p53 beeinträchtigte die Reparatur der Methylpurine nicht. In Zellen aller drei Linien nahmen die Adduktmengen innerhalb von 12 Stunden nach Behandlung mit MNU gleichermaßen ab. Die Menge an 7-Methylguanin sank auf 55 bis 80%, die an O6-Methylguanin auf 60 bis 70 %.
Als wichtigstes Beispiel für oxidative Schäden wurde 8-Hydroxyguanin (8-OH-G) untersucht. Das für den Nachweis der Methylpurin-Basen entwickelte Standardsystem wurde für die Auftrennung von Nucleosiden der DNA angepaßt, denn 8-OH-G wurde aus Gründen der Stabilität der Substanz auf der Ebene des Nucleosides, also als 8-Hydroxy-2'-desoxyguanosin nachgewiesen.
Da jedoch die Wechselwirkungen von 8-Hydroxy-2'-desoxyguanosin mit den funktionellen Gruppen der Ionenaustauschersäule zu gering waren, um die Elution wesentlich zu verzögern, wird dieses von anderen Produkten der enzymatischen DNA-Hydrolyse überlagert, die ebenfalls kaum ionischen Charakter besitzen. Es wurde gezeigt, daß dieses System für den Nachweis von 8-Hydroxyguanin nicht geeignet ist.

Two Ways of Binding Nucleotides

Crystal Structures of Nicotinamide Mononucleotide Adenylyltransferase from Homo sapiens and of Domain I of the Homing Endonuclease PI-SceI from Saccharomyces cerevisiae

Prepared by Erik Werner between May 1997 and May 2002 in the Heinemann Lab at Max Delbrück Center for Moleculare Medicine and at the Free University Berlin.

Download @ DARWIN-Server, Free University Berlin

Part 1:
Nicotinamide Mononucleotide Adenylyltransferase (NMNAT) from Homo sapiens in Complex with Nicotinamid Mononucleotide (NMN)
Collaboration with Mathias Ziegler (now: University of Bergen) and Manfrad Schweiger, Insitut for Biochemistry, Free University Berlin
Structure with max. 2.9 Å resolution, solved with the SAD-method (single-wavelength anomalous dispersion)

Part 2:
Domain I of the Homing Endonuklease PI-SceI from Saccharomyces cerevisiae
Collaboration with Wolfgang Wende and Alfred Pingoud, Institut for Biochemistry, Justus Liebig University Giessen
Structure with max. 1.35 Å resolution, solved with the molecular replacement method

Summary

Nicotinamide mononucleotide adenylyltransferase of Homo sapiens in complex with nicotinamide mononucleotide

Nicotinamide adenin dinucleotide (NAD⁺) is an important molecule as coenzyme in cellular redox reactions and signal-transduction pathways. The enzyme nictotinamide/nicotinate mononucleotide adenylyltransferase (NMNAT/NaMNAT) takes part in the biosynthesis of NAD⁺ by transferring the adenosine monophosphate moiety of ATP to nicotinamide/nicotinate mononucleotide. In the case of NaMN the product is nicotinate-adenin dinucleotide (NaAD⁺) which gets amidated by NAD⁺-synthetase. In the case of NMN, NAD⁺ gets synthesized directly.
The crystal structure of NMNAT from Homo sapiens in complex with NMN was solved to a maximum resolution of 2.9 Å with the SAD method (single wavelength anomalous dispersion). Final R_cryst and R_free values are 24.6 % and 28.6 % respectively. The structure of NMNAT consists of a six-stranded parallel b-sheet with helices on both sides, which in the core is the Rossmann fold. Electron density was observed for the ligand NMN but not for a loop of 37 amino acids, 109 to 146, that is positionally disordered. The structure of hNMNAT differs from the homologous proteins of M. thermoautotrophicum and M. jannaschii by this loop that contains a nuclear localization signal and by additional amino acids that form the helices H and I and the strand f in the human enzyme. Those secondary structure elements cause a different oligomerization compared to the archaeal proteins, but all occur as hexamer as biological unit. Protein-protein contacts between the monomers that form two trimers on top of each other are established between helices A, H and J as well as the loop between Helices J and K. The trimers are twisted with respect to each other, the b-sheets of subunits of different trimers arrange side by side in an antiparallel fashion and form a kind of a super-secondary structure but do not contact directly. Bacterial NMNAT occurs as monomer (E. coli) or dimer (B. subtilis) and in the case of E. coli NMNAT has further secondary structure elements.
The ligand NMN is bound by the amino acids Ser16, Lys57, Trp92, Thr95, Leu168 and Trp169, all on one side of the b-sheet. Comparison of the NMN complex with human NMNAT structures solved by other groups (the apoenzyme and the NAD⁺ complex) and with the archaeal and procarial homologs yield a model for ligand binding and synthesis. In the apoform, the enzyme is in an open state. Helices F and G on one side and the region around helix B on the other side have a greater distance than in the complex. NMN binds to this part of the ligand binding pocket, on one side of the b-sheet. ATP, the other reaction partner, is possibly attracted by a cluster of positively charged amino acids that only forms upon oligomerization. It could get transferred to the reaction center, possibly under participation of amino acids Lys58 and Arg231. ATP binds on the other side of the b-sheet. Binding is facilitated by Phe17, Gly156, Glu215 and Asn219 and most likely by the conserved residues Thr21, His24, Ser222, Thr224 and Arg227 which obviously bind the b- and g-phosphates. Upon substrate binding, the above mentioned elements approach and at the same time the C-terminus gets ordered (from residue 258 on). It covers parts of the NMN-binding pocket and of His24 and Lys58. Amino acids Gly15, Ser16, Phe17, His24 and Lys57 might participate in the synthesis reaction because they are locally close to the phosphodiester bond that is going to be formed. Dissociation of NAD⁺ and pyrophosphate PP_i goes along with relaxation of the protein and completes the reaction cycle.

Domain I of the homing endonuclease PI-SceI of Saccaromyces cerevisiae

The homing endonuclease PI-SceI of S. cerevisiae is an intein, an internal protein, embedded into the extein sequences of the 69 kDa subunit of the vacuolar membrane H⁺-ATPase. In a protein splicing process it cuts itself out of the protein precursor and combines the two exteins. Responsible is domain I of PI-SceI that at the same time accounts for most of the binding energy to the specific DNA sequence of at least 31 bp. The recognition sequence is the VMA1-Dvde locus of S. cerevisiae chromosome 8. This locus is the allele of the VMA1 genetic sequence (VMA: vacuolar membrane H⁺-ATPase) that is deficient for vde (VDE: VMA derived endonuclease = PI-SceI). Domain II of PI-SceI contains the nucleolytic center, which cuts the specific recognition sequence and initiates the insertion of the vde-gene ("homing"). It is a member of the LAGLIDADG family of homing endonucleases and binds the DNA only loosely.
The crystal structure of domain I of PI-SceI was solved with the molecular replacement method to a maximal resolution of 1.35 Å. Final R_cryst and R_free values are 15.0 % and 18.9 % respectively. Although four crystal structures of the whole protein were known already, the high resolution and the good definition of areas that were not or not well defined in the other structures give a view of further details. The goals to observe the whole protein sequence in the electron density and to produce protein-DNA cocrystals where not reached. Rather, protein crystals were observed in crystallization attempts with complexes. 96 of 217 amino acids take part in crystal contacts. Domain I of PI-SceI, or the core part of it, adopts the hint fold of the hedgehog/intein domain and consists mainly of b-strands. The active center of domain I, the protein splicing site, has cysteine 1 and two N-terminal extein residues but lacks the C-terminus of the intein, Asn454. The common model for the first step of the protein splicing reaction mechanism can be structurally confirmed. The side chain of Cys1 initiates the initial N-S acyl shift by a nucleophilic attack of the carbonyl carbon of Ala(-1). Subsequently follow a transesterification, formation of a succhimide and the final S-N acyl shift.
Residues Gln55 to Glu66 were not observed in the electron density due to local disorder. They obviously form a flexible loop that is suspected to take part in the tight binding of DNA by domain I. Further residues that are supposed to participate in DNA binding because of biochemical data, lie at the front side of a tongs-like subdomain that is formed by strands i, j and k and helices B and C. Most likely, helices D and E as well as strand l are also part of this subdomain because they also contain potential DNA-binding residues. A structural alignment of all known protein chains of PI-SceI domain I suggests, that besides the flexible residues Gln55 to Glu66 the amino acids Arg94, Arg90 and Arg87 have bigger, Tyr130 and Lys173 at least significant structural differences. Tyr176, Tyr420, Arg172 and Arg162, but also Lys112 and Lys124 on the other side are structurally constant. For the first, flexible group it can be suggested, that they possibly rearrange to facilitate DNA binding, for the latter, inflexible residues that they might take part in the initial positioning of the DNA.
A geometry based docking model makes the possibility of a movement of about 60º relative to the core visible. Four proven contact sites of PI-SceI and the recognition sequence were structurally aligned. Those are Asp218 and C^-3(bottom strand), Asp326 and G⁺³ (top strand), Tyr328 and G⁺⁴ (bottom strand) as well as His333 und T⁺⁹ (top strand), that means the nucleolytic active sites and two zero-length photo-crosslinks. The resulting model yields an orientation of the DNA relative to domain I that is not consistent with biochemical data and the distribution of surface charges. To reach agreement of biochemical data and the model, a rotational movement of the tongs-like subdomain (or parts thereof) was suggested that brings the strands i, j and k to close contact with the major groove of basepairs +16 to +18, the amino acids Arg90/Arg94 close to A¹⁴/T¹⁵/T¹⁶ of the top strand and Lys170/Lys173 close to the nucleotides 10 to 12.