[SA_scat] Interdisciplinary postdoc position in SAXS and bioinformatics at EMBL-Hamburg

Dmitri Svergun svergun at embl-hamburg.de
Thu Feb 3 13:31:31 GMT 2011


Dear All,

this is an announcement of the call for applications 
for EMBL Interdisciplinary Postdocs (EIPOD). The 
EIPOD positions are funded initially for three years  
and promote interdisciplinary research in biology. 
Attached below is a predefined EIPOD project in biological SAXS 
associated with the SAXS group in Hamburg. 
The application deadline is March, 20, 2011. 
The on-line application is available from 

http://www.embl.de/training/postdocs/eipod/

For further detail, please contact D.Svergun (Svergun at embl-hamburg.de)

With best regards   D. Svergun


“Cross-validation of macromolecular models in solution built from small
angle X-ray scattering”
Coordinator: D.Svergun
Partners: G.Kleywegt, A.-C. Gavin

The project aims at the joint use of the bioinformatics and macromolecular
crystallography (MX) to construct and validate the low resolution models
obtained by small-angle X-ray scattering (SAXS). This technique experiences
a renaissance in modern structural biology providing three-dimensional (3D)
models based on the scattering data from solutions and being ideally suited
for systemic studies of complex biological objects and networks. Recent
progress in instrumentation (high brilliance synchrotrons) and novel data
analysis approaches significantly enhanced the capabilities of SAXS in
structural biology [1]. In particular, 3D shapes at a resolution of ca 1-2
nm can be reconstructed ab initio and quaternary structure of complexes can
be modeled in terms of the high resolution models of the individual
subunits. 

Building 3D models from SAXS is inherently ambiguous as the method provides
low resolution information only. At present, objective criteria like
crystallographic free R-factor and structural assessment tools like WHAT IF
or CING are not present for SAXS-generated models. The validation of these
models becomes an extremely important issue in view of the growing requests
from the biological community to make these models available in the Protein
Data Bank (PDB).

The EIPOD will develop bioinformatic tools for a comprehensive validation of
the SAXS models under the guidance of D.Svergun (EMBL Hamburg), developing
advanced SAXS analysis methods [1]. The validation principles and approaches
will be devised in collaboration with G. Kleywegt, (Head of PDBe, EBI
Hinxton), an expert in the validation of protein models [2]. The EIPOD will
be involved in the work of the wwPDB Task Force recently created to prepare
conditions for inclusion of the SAXS models into PDB. The developed tools
will be tested and applied to a challenging proteomics-scale project. The
EIPOD will take part in preparation and SAXS analyses of the protein
complexes selected from the ongoing biochemical screen in the A-C.Gavin’s
group (EMBL Heidelberg), exploring new types of biological networks [3]. The
combinatorial SAXS measurements will be performed utilizing a microfluidic
device on a new high brilliance EMBL synchrotron beamline in Hamburg. The
available high resolution structures of some complexes will be used to test
the validation criteria. The latter will then be applied in the structural
characterization of the complex formation in the entire interactome
(hundreds of proteins) as a proof of principle of the validation approach.

The research includes a synergistic use of structural, biochemical and
bioinformatics methods, providing an excellent opportunity for a biologist,
physicist or mathematician (preferably with bioinformatic, crystallographic
or NMR background) to develop complementary skills during the work on this
challenging and highly interdisciplinary project. 

1.	Mertens, H. D. T. & Svergun, D. I. (2010). Structural
characterization of proteins and complexes using small-angle X-ray solution
scattering. J Struct Biol 172, 128-141.
2.	Kleywegt, G.J. (2007) Quality control and validation. Methods Mol
Biol. 364, 255-272.
3.	Kühner S., van Noort V., Betts M.J., Leo-Macias A., Batisse C., Rode
M., Yamada T., Maier T., Bader S., Beltran-Alvarez P., Castaño-Diez D., Chen
W.H., Devos D., Güell Cargol M., Norambuena T., Racke I., Rybin V., Schmidt
A., Yus E., Aebersold R., Herrmann R., Böttcher B., Frangakis A.S., Russell
R.B., Serrano L., Bork, P. & Gavin, A.C. (2009) Proteome organization in a
genome-reduced bacterium. Science, 326, 1235-1240



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