Download Synthesis of fluorescent lipid-polymer probes and study of their

 Synthesis of fluorescent lipid‐polymer probes and study of their insertion in lipid bilayers for optical imaging of virus/host cell interaction Laboratory “Engineering of Polymer Materials” in Lyon, France Hepatitis C affects 120 to 170 million people worldwide and is a chronic infection leading to liver cirrhosis and hepatocellular carcinoma. New drugs released in 2011 raised hope for patients, however they meet serious problems of tolerance. The entry step of hepatitis C virus (HCV) into its host cells (hepatocytes) still needs to be understood. This comprehension is essential for the development of innovative antiviral strategies. The HCV exists under 3 forms in patient's serum: (i) enveloped in a lipid bilayer (HCV pseudoparticles), (ii) non‐enveloped and (iii) associated to lipoproteins. 1 In the last years, we have developed lipid‐polymer conjugates able to interact with artificial lipid bilayers 2 and fluorescent lipid‐
polymer probes that efficiently label living cells such as HeLaand T lymphocytes. The aim of this project is to elaborate novel lipid‐polymer probes to label HCV viral particles and to follow their interaction and entrance in the host cells. The lipid‐polymer probes are synthesized from biocompatible polymer chains bearing a phospholipid moiety at one‐end and multiple fluorophores along the polymer chain. Such polymer probes generally exhibit an improved brightness compared to the corresponding molecular probes. 3 This strategy (already applied to chromophores emitting in the visible or the far red) will be extended to NIR fluorophores (convenient to escape the self‐fluorescence from the host cells) and to fluorophores especially designed to enable a fine localization of biological events (like the entrance of a virus inside a cell). The PhD training will be included in a larger multidisciplinary project with biologists and will consist in two main parts: • The synthesis of fluorescent lipid‐polymer probes; their structure (size of the polymer chain, nature of the phospholipid, number of chromophores per chain) will be optimized in order to efficiently label the viral particles. • The study of interactions of these lipid‐polymer probes with model lipid bilayers such as liposomes and LipoParticles (i.e., polymer particles coated with lipid layers) 4 will be achieved to select the relevant lipid‐polymer probes in terms of lipid layer insertion and membrane labeling. The evaluation of the ability of the lipid‐polymer probes to label HCV viral particles will be carried out with biologists collaborating to the project. The candidate should have a Master degree in organic chemistry or polymer synthesis or polymer physico‐chemistry and should have an interest for biology and microscopy. The PhD training will take place both at University Claude Bernard Lyon 1 (with Dr Catherine Ladavière) and at Ecole Normale Supérieure de Lyon (with Dr Arnaud Favier and Dr Marie‐Thérèse Charreyre). Contact: marie‐therese.charreyre@ens‐lyon.fr
http://www.imp.cnrs.fr/,http://www.ens‐lyon.fr/Joliot‐Curie/
1
Bartenschlager R., Penin F.,Lohmann V. and Andre P.,Trends Microbiol. 2011, 19, 95‐103. Bathfield M., Ladavière C., Charreyre M‐T. et al., Macromolecules 2008, 41, 8346‐8353. 3
Cepraga C., Favier A., Charreyre M‐T. et al., PolymerChemistry 2013,4, 61‐67. 4
Troutier A.L., Véron L., Delair T., Pichot C., Ladavière C., Langmuir 2005, 21, 9901‐9910. 2
INGENIERIE@LYON
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April 16, 2013
Letter of support from institut Carnot Ingénierie@Lyon (I@L) : thesis project
« Synthesis of fluorescent lipid-polymer probes and study of their insertion in lipid bilayers
for optical imaging of virus/host cell interaction”
Beca para estudios de doctorado CONACYT/ Ambajada de Francia
To whom it may concern,
1
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We have been greatly delighted to forward to the 12 academics laboratories of the institut
Carnot I@L (www.ingenierie-at-lyon.org), the call for mexican applications for a 3-year PhD
fellowship in France.
By supporting the thesis proposal supervised by the IMP laboratory (Lyon 1, INSA de Lyon)
labelized I@L and the Joliot Curie laboratory (ENS Lyon), we are convinced that the CONACYT
and Embassy of France’s initiative will efficiently contribute to the development of
international academic partnerships, and thus promote the development of innovation,
which is well consistent with our own objectives.
We therefore strongly support the referenced PhD project within the proposed framework.
Sincerely,
Pr Régis DUFOUR,
Chief Executive Officer of I@L