[ccp4bb] PhD Position in serial crystallography and drug design, the European Synchrotron Radiation Facility, Grenoble, France

[Max Nanao <max.nanao@ESRF.FR>]

Hi All,
We have an exciting opportunity for a PhD project on drug design and 
serial crystallography at the ESRF. The project will be in collaboration 
with the Servier Institute. More details can be found on the ESRF 
website (https://esrf.gestmax.eu/1432/1/phd-student-id23-2/en_US), or 
below


CONTEXT & JOB DESCRIPTION
X-ray crystallography is a critical tool in modern drug design. Ligand 
and/or fragment screening campaigns for drug design are typically 
carried out by collecting diffraction data at 100 K from large (> 30 
mm), robust, well diffracting crystals. However, there is increasing 
evidence that crystal soaking protocols are more efficient when applied 
to smaller crystals and that the cryo-cooling of crystals may obscure 
biologically relevant information. Post ESRF-EBS X-ray beams will allow 
us to apply recently developed multi-crystal (MDX) data collection 
protocols to complexes of micro-crystals with small molecules. However, 
how best to combine the partial data sets obtained in MDX in order to 
obtain the best electron density for bound fragments or ligands and the 
best analysis of modes of binding to their target molecules is an area 
requiring optimisation.

The aims of this PhD work are:

1). To provide a systematic analysis of the effect of crystal size of 
the ligand/fragment occupancy obtained in soaking experiments;

2). To improve and optimize protocols for the combination of MDX data 
sets using enhanced protocols for hierarchical cluster analysis (HCA) 
and genetic algorithms (GAs), areas which are being actively developed 
at ESRF.

The project proposed here is based on a combination of methodology 
development at the ESRF and access to material, training expertise and 
insight from IDRS Servier, Suresnes, France. This opportunity will thus 
provide an unrivalled opportunity for a young scientist interested in 
optimising structure-based drug design processes, which exploit 
microcrystals. During the PhD work, the student will learn experimental 
methodology (protein production and purification, crystallisation, 
diffraction data collection, data analysis) and interpretation of 
real-world results in an area designed to overcome major bottlenecks in 
the drug design process.

Further information may be obtained from Max Nanao (tel.: +33 (0)4 76 88 
4087, email: nanao@esrf.fr).

EXPECTED PROFILE
Degree allowing enrollment for a PhD (such as MSc, Master 2 de 
Recherche, Laurea or equivalent) in chemistry, physics, materials 
science or closely related science
A background in Statistics is desirable as is some knowledge of 
Structural Biology
The candidate should show a strong aptitude for team working and have 
excellent communications skills
Proficiency in English (working language at the ESRF)
WORKING CONDITIONS
Contract of two years renewable (subject to satisfactory progress) for 
one year.

The ESRF is an equal opportunity employer and encourages diversity.





--
Max Nanao
European Synchrotron Radiation Facility
Structural Biology Group
71,Avenue des Martyrs
F-38000 Grenoble
Tel: +33.(0)4.76.88.40.87
ORCID: 0000-0002-6340-1376

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