Marc N. Offman, PhD

postdoc@

I12, Chair of Prof. Rost

Technische Universität München

Fakultät für Informatik

Boltzmannstraße 3,

85748 Garching, Germany

Mail: offman@rostlab.org

Phone: +49 89 289 17831

Fax: +49 89 289 19414

Room: 01.09.057

Research Interests

o Molecular Dynamics Simulations

o Single Nucleotide Polymorphism Analysis

o Protein Engineering

o Protein Modelling & Refinement

Molecular Dynamics Simulations

Proteins are intrinsically flexible molecules, thus function is often associated to flexibility. Experimental methods to determine protein flexibility are expensive and often time consuming. Over the past few years an efficient alternative, molecular dynamics (MD) simulations, more and more proved to be a powerful tool to yield information on protein dynamics. In MD methods, successive conformations of proteins can be calculated using Newton’s law of motion. As a result a trajectory is produced that describes how the positions and velocities of all atoms vary with time. This way important observations can be made, helping to understand proteins and eventually associated diseases better.

Protein Engineering

Proteins are central to most biological processes and their spectrum of functions is seemingly endless. Given that proteins are found in almost any living forms and each organism had to adapt to evolutionary pressure over million of years, a large number of different proteins have evolved. Some of these proteins could potentially be used as drugs, others need to be adapted (engineered), and for some purposes new proteins need to be designed. In protein engineering/design either known proteins are adapted in order to meet certain criteria such as increased stability, function, activity and recognition, or novel protein folds are created. Given the fact that proteins are large, complicated molecules with a huge number of degrees of freedom, protein engineering seems to be an unsolvable task. Nevertheless, methods are under constant development and show some success, as engineered proteins can already be used as therapeutics and as tools for cell biology.

Protein Modelling & Refinement

Malfunctioning proteins often cause diseases. Proteins are three-dimensional molecules with different functions, each defined by a gene. Much effort has been invested in sequencing the genomes of various species, including the human genome, however the number of known protein structures lags far behind. Exploring these unknown structures can either be done experimentally, involving a lot of time and costs, or computationally, for which further development is needed. The aim of my project is to use computational methods to built models for protein structures and refine these models to an accuracy level of experimentally determined protein structures.

Servers & Software

o 3D Jigsaw 3.0:

http://bmm.cancerresearchuk.org/~populus/

o POPULUS protein modelling & refinement software:

http://bmm.cancerresearchuk.org/~offman01/populus.html

o Hydrophobicity applet:

http://bmm.cancerresearchuk.org/~offman01/hydro.html

Teaching

o Hauptseminar Bioinformatik (2011)

o Practical Protein Structure and Function Analysis (2011)

CV

Personal Details

Name:	Dr. Offman
First name:	Marc Nathan
Date of birth:	18^th May 1979
Place of birth:	Munich
Nationality:	German
Marital status:	married

Career History

From 2010	I12, Chair of Professor Rost, Technical University Munich, Germany § Large-scale Molecular Dynamics Simulations of SNPs § Protein Engineering
2008 – 2010	Weizmann Institute of Science, Department of Biological Chemistry – Rehovot, Israel, Postdoctoral position § Protein Engineering of Glucocerebrosidase, a protein used for enzyme replacement therapy in Gaucher disease § Project coordination: Israel-Poland-UK § Algorithm development § Structural and statistical analysis § Scientific writing
2004 – 2008	Biomolecular Modelling Laboratory, Cancer Research UK – London, UK, PhD position § Development of new algorithms for Protein Modelling and Refinement § Protein Engineering in Drug Design § Structural and statistical analysis § Web server development
2003 – 2004	Technische Universität Munich, Department for Genome Oriented Bioinformatics – Munich, Germany, Graduate student position § Protein protein interactions § Data mining and analysis
2001 – 2002	Paper Technology Services – Munich, Germany IT support (part-time) § Network administration § Server configuration § Workstation configuration § On Site support
2000	Sigma Aldrich Diagnostics, Germany and Europe – Deisenhofen, Germany (full-time) § Sales analysis § Data Warehousing § Customer Support for European Distributor (AVM Austria)

Education

2004 – 2008	Ph.D. Biochemistry and Molecular Biology, Cancer Research UK / UCL, UK § Protein Modelling, Refinement and Engineering
2000 – 2004	B.Sc. in Bioinformatics, Technische Universität Munich, Ludwig Maximillian Universität Munich § Sequence Features of Protein Protein Interaction Interfaces

Fellowships and Awards

2008 – 2010	Minerva Long-term Fellowship
2004 – 2008	Cancer Research UK Ph.D. Scholarship
2004 – 2008	Barbara Mary Hill Memorial Fund Fellowship
2004 – 2008	B’nai B’rith Leo Baeck Lodge Scholarship
1999	Buchpreis des Fonds der Chemischen Industrie

Languages

German	Mother tongue
English	Excellent command, written and spoken
French	Good command, written and spoken
Hebrew	Basic command, written and spoken

Computing

§ Programming languages: C++, Java	§ Scripting: Perl, Python
§ Databases: PSQL, MySQL, Access	§ HTML
§ MS-Office package	§ SAP SD Module

Conferences and Courses

07/2011	Invited speaker at ISMB/ECCB
07/2011	ISMB/ECCB Conference – Vienna, Austria
Since 2011	ISCB Member
03/2010	GROMACS Workshop on Molecular Dynamics simulations – Rehovot, Israel
07/2007	Modern Drug Target Crystallography and Structure Based Drug Discovery – San Diego (CA), USA
10/2006	GRADPEST, Scientific communications course, Cancer Research UK – London, UK
12/2004	6^th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction – Gaeta, Italy
10/2003	German Conference on Bioinformatics – Munich, Germany

Publications

Zimprich A., Benet-Pages A., Struhal W., Graf E., Eck S.H., Offman M.N. et al. (2011). A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease. Am J Hum Genet, 89(1):168-175.

Offman M.N., Krol M., Rost B., Silman I., Sussman J.L., Futerman A.H. (2011). Validation of a Molecular Dynamics Protein Structure Prediction: Comparison of an MD model with the X-ray structure of the N370S acid-β-glucosidase mutant that causes Gaucher disease. Protein Engineering, Design & Selection, (submitted).

Offman M.N., Krol M., Patel N., Krishnan S., Saha V., Bates P.A. (2011). Rational engineering of L-asparaginase reveals importance of dual activity for cancer cell toxicity. Blood, 117:5.

Offman M.N., Krol M., Silman I., Sussman J.L., Futerman A.H. (2010). Molecular basis of reduced glucosylceramidase activity in the most common Gaucher disease mutant, N370S. Journal of Biological Chemistry, 285:53.

Patel N., Krishnan S., Offman M.N., Krol M., Moss C.X., Leighton C., van Delft F.W., Holland M., Liu J., Alexander S., Dempsey C., Ariffin H., Essink M, Eden T.O.B., Watts C., Bates P.A., Saha V. (2009). A dyad of lymphoblastic lysosomal cysteine proteases degrades the antileukemic drug l-asparaginase. Journal of Clinical Investigations, 119:7.

Offman M.N., Tournier A.L., Bates P.A. (2008). Alternating evolutionary pressure in a genetic algorithm facilitates protein model selection. BMC Structural Biology, 8:34.

Offman M.N., Fitzjohn P.W., Bates P.A. (2006). Developing a move-set for protein model refinement. Bioinformatics, 22(15):1838-1845.

Offman M.N., Nurtdinov R.N., Gelfand M.S., Frishman D. (2004). No statistical support for the correlation between the positions of protein interaction sites and alternatively spliced regions. BMC Bioinformatics, 5:41.

Contreras-Moreira B., Fitzjohn P.W., Offman M.N., Smith G.R., Bates P.A. (2003). Novel use of a genetic algorithm for protein structure prediction: searching template and sequence alignment space. Proteins, 53:424-429.