Postdoc Lifesearch WP1 EN 2013 .pdf


Nom original: Postdoc Lifesearch WP1 EN 2013.pdf
Titre: Postdoc Lifesearch WP1 EN 2013
Auteur: LAURENT MARTINEZ

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Post-doctoral position in physiopathology
“HDL-related therapy” assessment in animal models

Description of the company
Lifesearch is a new company in the biotechnology field which develops projects of R & D in
collaboration with leading research organizations (INSERM, CNRS, CEA). In the project presented
here, the post-doc recruited by Lifesearch will work within the Institute of Cardiovascular and
Metabolic Diseases, UMR1048 (INSERM - Université Paul Sabatier, Toulouse, France).
Research project
Cardiovascular diseases are number one of mortality causes in Western societies. The
protective effect of HDL-cholesterol (High Density Lipoprotein cholesterol or “good cholesterol”) in
cardiovascular disease is supported by many epidemiological studies and is now widely accepted.
Indeed, HDL-C has the unique ability to excreted cholesterol excess out of the body through
hepatic biliary lipid secretions. In addition, HDL-C exerts direct vascular beneficial functions by
protecting coronary arteries.
Lowering LDL-C (Low Density Lipoprotein cholesterol or “bad cholesterol”) is possible since
1987 with the first blockbuster statin (LDL-C lowering drug). The antidyslipidemics market is
since driven by statins, which account for 87% of it. However, even in high-risk patients treated
to aggressive LDL-C goals, coronary events still occur at a high rate and low HDL-C is a major risk
factor. Thus, a natural next step in the search for therapies to reduce cardiovascular morbidity
and mortality further involves raising HDL-C levels and/or improving HDL-C functions.
While some existing therapies can raise HDL-C levels, their major impact concern other lipid
targets, like LDL-C or triglycerides and their effects on HDL are modest. Therefore new therapies
specifically targeted to HDL (= “HDL-therapy”) are needed.
The research project aims to evaluate in animals the effect of a new molecule on HDL
metabolism and the development of atherosclerosis. This will include studying the metabolic
and vascular atheroprotective effects of this molecule on mice models of experimental
atherosclerosis. In these models, the reverse cholesterol transport will be measured in vivo.
Plasma kinetics of radiolabeled HDL and lipid and genetic analyzes will be performed (plasma
lipoprotein profile, lipid dosage in plasma, liver and gallbladder, expression of hepatic genes,
etc...). The effect of this molecule on the development of atherosclerosis will also be assessed.
Experience required
Outstanding skills in animal studies and surgery are requested, e.g.: liver perfusion,
gallbladder cannulation, iv and ip injection and Alzet pump, analyze of atherosclerosis lesions in
aortic arch, to develop nutritional regimes and experimental protocols, track animals during the
protocols.
Also a good knowledge in biochemistry and lipoprotein metabolism (to know how to analyze lipids
profile and HPLC/FPLC etc…) is wished.

The position is available for 2 years as soon as December 1st 2013. Interested applicants
should submit a motivation letter, a curriculum vitae including a full list of publications and
references to laurent.martinez@inserm.fr. Submissions should include the mailing label “Postdoctoral position”.


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