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 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.
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.