What is the background of the project?
LXR and FXR are nuclear receptors activated by nutritional derived ligands: oxysterols (oxidized metabolites derived from cholesterol) and bile acids, respectively. Epidemiologic studies pointed out the deleterious role of a high fat diet in the development of prostate cancer and male infertility in westernized countries. Our team develops two main projects. 1) In prostate cancer, our work demonstrated LXR are a potential pharmacological target in the treatment of this cancer. The aim of the project is to analyze the expression levels of LXR alpha and LXR beta, as well as some of their target genes in tumors from patients that underwent a radical prostatectomy. Normal contra-lateral tissues will be studied as well. This will be done by qPCR and/or western blot analysis. 2) In male infertility, we showed that FXR could regulate testis functions. The aim of the second project is to analyze the expression of the bile acids receptor and investigate their respective physiological functions in the various cells. This will be done using human samples and KO mice.
Preliminary readings: prostate cancer, male infertility, nuclear receptors, RNA and protein quantification
To manipulate human samples to extract RNA and proteins and measure the various expression levels. The student will be associated to every posters and/or papers that will be using her/his data.
You will acquire:
Strong skill in bench work regarding expression measurement, nuclear receptor functions, biology of prostate cancer, animal models of prostate tumors.
Pommier AJC, Alves G, Viennois E, Bernard S, Communal Y, Sion B, Marceau G, Damon C, Mouzat K, Caira F, Baron S, Lobaccaro JMA. Liver X Receptor downregulates AKT survival signaling in lipid rafts and induces apoptosis of prostate cancer cells. Oncogene. 2010; 29(18):2712-23.
Volle DH, Duggavathi R, Magnier BC, Houten S, Cummins CL, Lobaccaro JMA, Verhoeven G, Schoonjans K, Auwerx J. The small heterodimer partner is a gonadal gatekeeper of sexual maturation in male mice. Genes Dev 2007 Feb 1;21(3):303-15.
Volle DH, Mouzat K, Duggavathi R, Siddeek B, Déchelotte P, Sion B, Veyssière G, Benahmed M, Lobaccaro JMA. Multiple roles of the nuclear receptors for oxysterols LXR to maintain male fertility. Mol Endocrinol. 2007; May;21(5):1014-27. Epub 2007 Mar
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
A strong skill is molecular biology is needed.