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LabTAU - Unité de recherche U1032
Applications des ultrasons à la thérapie
Jean-Yves Chapelon, directeur
PhD at LabTAU (Lyon, France) - Ultrasound-induced transformation of bacteria
The laboratory LabTAU is looking for a PhD candidate for working on the application of
ultrasonic cavitation to transfect bacteria in vitro.
The LabTAU, UMR-S 1032, is fully affiliated to the University Claude Bernard Lyon 1 (UCBL1) and to
the French National Institute for Health (INSERM). Research at LabTAU aims at developing and
optimizing innovative ultrasound therapies from bench to bedside. The team gathers interdisciplinary
research scientists and professors from INSERM, UCBL1, and clinicians from Lyon’s University
Hospitals and Regional Cancer Center Léon Bérard. The laboratory has worldwide renowned
expertise in (i) ultrasound physics (ultrasound- and shear-wave propagation, bubble dynamics),
metrology and bioeffects (thermal, cavitation) (ii) design and manufacturing of image-guided
therapeutic transducers for thermal ablation and drug delivery, (iii) clinical transfer, (iv) fundamental
modeling of therapeutic ultrasound beam, simulation and optical characterization of bubble dynamics,
(v) ultrasound-based methods of transfection in vitro and in vivo, (vi) ultrasound molecular imaging
with targeted contrast agents, (vii) ultrasound-mediated drug delivery with liposomes and microemulsions. LabTAU with its quality insurance system (certified ISO9001 since 2008) has a long history
in collaborating with industrial partners.
Transformation of bacteria is a widespread technique often used in molecular biology laboratories.
This technique allows the introduction of a gene into bacteria. The DNA transfer in bacteria is most
often done using heat shock or electroporation. The LabTAU has developed a device using confocal
transducers that allow a tight control of the ultrasonic cavitation activity to transfect eukaryotic cells.
This device has also been successful at transforming yeast and the bacteria strain E.coli.
The objective of the proposed PhD project is to further develop our knowledge in transformation of
bacteria using ultrasound and design an ultrasound-based transformation tool for bacteria.
In a first stage, the candidate will investigate the biological protocols to optimize the transformation of
different bacteria strains including Gram+ and Gram- bacteria. These can include strains from clinic.
This stage includes the choice of the Gram+ and Gram- bacteria strains, the plasmid construction
compatible with these strains, and the strains pre-culture. The aim being a significant reduction in the
pre-treatment operations needed.
In a second stage, the ultrasonic device will be upgraded to allow the ultrasonic exposure of 96-well
plates. Optimization of the exposure conditions will also be done in this case. The combination of
electroporation with sonoporation will be investigated to further optimize the method.
On a technological plan, it would be interesting to estimate the impact of the ultrasound settings on the
transfection efficacy. Ultrasound parameters affect the cavitation bubble size and thereby the poration
required for the bacteria that are smaller than eukaryotic cells. Plasmids of various sizes will be used.
On a methodological plan, one could study the effect of adjuvants. Addition of adjuvants could allow a
better permeabilisation of the bacteria membrane (CaCl2, photo sensitizer), or facilitate the coupling
between the bacteria and the plasmid (polarization, use of liposomes).
The in vitro tests will consist in:
 Set up a strict protocol for transformation of the Gram- bacteria E.coli (establish the plasmid
and bacteria concentrations, the necessary stages before ultrasonic treatment).
 Use this protocol for evaluation on different Gram- bacteria.
République française
LabTAU - Unité de recherche U1032
Bâtiment INSERM, 151 Cours Albert Thomas
69424 Lyon Cedex 03, France
Tél : 04 72 68 19 30 Fax : 04 72 68 19 31
E-mail : [email protected]
LabTAU - Unité de recherche U1032
Applications des ultrasons à la thérapie
Jean-Yves Chapelon, directeur


Establish a transformation protocol for specific Gram+ bacteria (Bacillus subtilis, Lactococcus
lactis…)
Estimate the effect of combining electroporation and sonoporation on the efficacy of the
bacteria transformation.
Applicants must hold a Master degree in biology or biomedical engineering with expertise and interest
in molecular and cell biology in relation to infectious diseases: Plasmid construction and analysis,
PCR, cell and bacterial culture, cell labeling, fluorescence and light microscopy, Western blot.
Competences in medical acoustics will be considered an asset.
The proposed project is expected to be further developed by an ambitious and creative candidate. The
candidate is expected to be highly motivated for a collaboration with another academic laboratory
specialized in infectious diseases.
Applications (3 pages max.), including a CV, a cover letter and contact information of referees should
be sent to Cyril Lafon ([email protected]) before May 25, 2015. Candidates will be invited for
interviews before June 14. The selected candidate will compete in a regional contest from the doctoral
school EDISS (http://www.ediss-lyon.fr) in order to obtain a 3-year fellowship starting in October 2015.
République française
LabTAU - Unité de recherche U1032
Bâtiment INSERM, 151 Cours Albert Thomas
69424 Lyon Cedex 03, France
Tél : 04 72 68 19 30 Fax : 04 72 68 19 31
E-mail : [email protected]