Sent on behalf of Guillaume Duménil, Institut Pasteur.

Research Project

We are looking for a highly motivated post-doctoral scientist who would like to 
decipher,
at atomic resolution, how newly discovered small-molecule inhibitors disable 
the type IV
pili of pathogenic bacteria. These virulence nanomachines are essential for host
colonization and represent an untapped source of antibacterial targets. 
Building on our
discovery of potent inhibitors that block pili surface display (Aubey et al., 
PNAS 2019) and
on recent chemoproteomic work that revealed their protein targets, your mission 
will be
to determine the binding sites and to unravel the complete mode of action of 
these
compounds. First steps of the work will rely on single-particle cryo-EM and 
X-ray
crystallography, complemented by enzymatic, biophysical and functional assays 
in live
bacteria. By integrating structural information with mechanistic data you will 
guide
medicinal-chemistry efforts aimed at turning these leads into first-in-class 
antibiotics.

Host lab

The project is funded for at least two years and will be carried out in the 
Pathogenesis of
Vascular Infections Unit headed by Guillaume Duménil at the Institut Pasteur, a 
vibrant
campus in the heart of Paris that hosts more than 150 research groups. You will 
join an
interdisciplinary team of microbiologists, structural biologists, cell 
biologists and
biophysicists. You will have privileged access to state-of-the-art core 
facilities, including
Titan Krios and Glacios microscopes, a fully equipped crystallography platform,
advanced computing clusters, proteomics and BSL-2/3 imaging facilities. The 
institute
provides numerous training courses, an active post-doctoral association, sports
facilities and competitive salaries with full social benefits.

Knowledge and skills

Candidates should hold (or be about to obtain) a PhD in structural biology, 
biochemistry,
biophysics or a related discipline. Demonstrated experience in recombinant 
protein
expression and purification as well as in cryo-EM and/or macromolecular 
crystallography
is essential; familiarity with cryo-ET, membrane-protein reconstitution, 
chemical biology,
drug design, medicinal chemistry, basic scripting and/or bacterial genetics 
will be
considered advantageous. We value intellectual curiosity, rigor, the ability to 
work in a
team and strong communication skills in English; knowledge of French is not 
required.

Recruitment process

Applications will be reviewed continuously until the position is filled, with 
an ideal start
early 2026 (date negotiable). Please send a single PDF containing a cover 
letter outlining
your research interests and suitability for the project, a detailed CV with 
publication list,
and the names and e-mail addresses of two to three referees to Dr Guillaume 
Duménil
([email protected]). Informal enquiries are welcome. Come and help us
reveal the structural blueprints for tomorrow’s antibiotics.

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