Marc N. Offman, PhD

 

postdoc@

 

 

I12, Chair of Prof. Rost

Technische UniversitŠt MŸnchen

FakultŠt fŸr Informatik

Boltzmannstra§e 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 NewtonÕs 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:

18th 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 UniversitŠt 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 UniversitŠt Munich, Ludwig Maximillian UniversitŠt 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

BÕnai BÕrith 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

 

6th 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.