Disciplines Biologie Cellulaire
Laboratoire INSERM_U 1116
Institution d'accueil Université de Lorraine
Lorraine Université d’Excellence (LUE) Program is inviting applications for a post-doctoral position (100 %, 18 month) on telomere dynamics and accelerated arterial aging within the project IMPACT «Geenage» («Functional Genomic, Epigenomic and ENvironment interplay to IMPACT the understanding, diagnosis and management of healthy and pathological AGEing»).
LUE IMPACT GEENAGE. The ambition of GEENAGE is to produce new strategies of diagnosis and management of healthy and pathological ageing by targeting the functional consequences of the interplay between genes, epigenome and environment.
Duration: 18 months post-doctoral position available
Telomeres are defined as non-coding repetitive DNA sequences (TTAGGG) located at the ends of chromosomes Telomere length (TL) is genetically determined at birth, decreasing thereafter with age. At the cellular level, short TL have consequences on chromosome integrity, chromatin stability and cellular replicative capacities. Clinical studies have shown that short TL is associated with age-related cardiovascular alterations and diseases such as stiffness, atherosclerosis and heart failure, and diminished survival in the elderly. We have shown in longitudinal cohorts with long term sequential measurements of telomere length and cardiovascular phenotypes that short LTL precede the metabolic disorders and the atherosclerotic lesions, suggesting that short telomeres are significant bio-determinants of age-related vascular lesions
We make the hypothesis that short TL at the level of hematopoietic cells (HSC) measured on leucocytes denotes diminished HSC-mediated vascular repair capacity increasing thus the vulnerability for developing age-related arterial email@example.com
We have shown that the difference in TL between leukocytes-LTL (representing the highly proliferative hematopoietic system) and skeletal muscle (a low-proliferative tissue) is:
– more pronounced in patients with atherosclerotic cardiovascular disease than in controls and
– established during the two decades of life, suggesting that the LTL shortening during early life plays a major role in the development of age-related arterial diseases later in life.
Our goal is to study the role of telomere dynamics and their determinants, in the in the pace of arterial aging. We develop several translational research programs in large cohorts of different ages –from new-borns to very old adults.
The present post-doc project is focused on the study of the role of telomeric dynamics on the phenotype of progenitor endothelial cells.
Our research group (Telomeres and Arteries: TELART) combines a clinical research department (Geriatric Department and Center of Clinical Investigations) at the University hospital (CHRU) of Nancy for the study of arterial function and structure in clinical cohorts. Our group has developed translational research in this field for more than 25 years with significant publications. Our laboratory (INSERM U1116) for the cellular and telomere studies is located in the same campus as the clinical research department.
The methodological aspects are of major importance for the development of this translational research: creation and arterial phenotyping of cohorts; methods to measure TL in several tissues, in vitro cellular studies.
The TELART group is composed by 3 physicians, 1 Clinical Research Engineer, 1 Research Nurse, 1 PhD on Molecular Biology, 1 PhD student and 1 lab technician.
-Applicants should have a strong expertise in progenitor cell biology and good skills in primary cell culture and stem cell handling. -They should have some notions in the field of age-related cardiovascular diseases -Applicants should be able to conduct his/her research independently but also to work in a team. -The project will require a wide variety of techniques including flow cytometry, fluorescence-activated cell sorting (FACS), cellular and molecular imaging, reverse transcription polymerase chain reaction, Western blot analysis and ELISA. The applicant should not necessary have experience in all these techniques but he will probably have to get expertise on some of them
– Benetos A, Toupance S, Gautier S, et al. Short Leukocyte Telomere Length Precedes Clinical Expression of Atherosclerosis: Blood-and-Muscle Model. Circ Res. 2017 Dec 14. pii: PMID: 29242238. – Toupance S, Labat C, Temmar M, et al. Short Telomeres, but Not Telomere Attrition Rates, Are Associated With Carotid Atherosclerosis. Hypertension. 2017 Aug;70(2):420-425. PMID: 28630210. – Benetos A, Aviv A. Ancestry, Telomere Length, and Atherosclerosis Risk. Circ Cardiovasc Genet. 2017 Jun;10(3). pii: e001718.PMID: 28615296. – Verhulst S, Dalgård C, Labat C, et al. A short leucocyte telomere length is associated with development of insulin resistance. Diabetologia. 2016 Jun;59(6):1258-65. doi: PMID: 27020448. – Benetos A, Dalgård C, Labat C, et al. Sex difference in leukocyte telomere length is ablated in opposite-sex co-twins. Int J Epidemiol. 2014 Dec;43(6):1799-805. PMID: 25056338; – Benetos A, Kark JD, Susser E, et al. Tracking and fixed ranking of leukocyte telomere length across the adult life course. Aging Cell. 2013 Aug;12(4):615-21. PMID: 23601089; – Daniali L, Benetos A, Susser E, et al. Telomeres shorten at equivalent rates in somatic tissues of adults. Nat Commun. 2013;4:1597. PMID: 23511462;
Type de financement : Contrat de travail
Montant du financement: 2000 € Net / mois
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