Ageing in hibernating ground squirrels: exploring the role of telomerase and ALT mechanisms in seasonal telomere changes
Understanding the cellular mechanisms implicated in the process of ageing has been the focus of evolutionary biologists for decades. Telomeres – and more specifically telomere shortening or elongation rates – have been identified as key components of the aging process. Telomeres are non-coding genomic DNA sequences located at the end of linear chromosomes, whose primary role is thought to prevent the loss of genomic function by allowing the genomic rescue system to distinguish chromosome ends from accidental DNA breaks. However, telomere sequences are highly sensitive to oxidative stress and imperfectly replicated at each cell division, resulting in progressive erosion over time. Until recently, telomeres were seen as a hallmark of ageing, progressively shortening over time until cell apoptosis or senescence. The loss of telomere functionality has been correlated to the accelerated aging process. However, current data shows that cellular telomeres can be rejuvenated even in adult tissues, owing to maintenance mechanisms including telomerase activity (a ribonucleoprotein specialized in rebuilding telomeres) and/or alternative telomere lengthening through recombination (ALT) processes. Interestingly, several recent studies suggest that hibernating mammals may actually be able to restore cellular telomere length on a seasonal basis, but the mechanisms implicated in these dynamic changes (telomerase activity or ALT, or both) remain untested. In addition, how such changes are related to organism age and fitness remain unknown.
This Master’s (M2) project will investigate the links between seasonal telomere dynamics, telomere maintenance processes, and fitness in a hibernating rodent, the Columbian ground squirrel (Urocitellus columbianus). Our previous research has shown that these animals show dynamics patterns of telomere reconstruction following hibernation and loss over the summer breeding season. The candidate will be responsible for determining the mechanisms responsible for these dynamics and how they relate to individual reproductive success. They will benefit from samples already collected in the field and from a long-term life history data base providing information on individual age, reproductive success, past breeding experience. The tasks will include (1) laboratory analyses of samples to determine telomere length, telomerase activity, and DNA instability biomarkers related to telomere dysfunction; (2) statistical analyses of inter-individual variability in telomere maintenance and relations to fitness. The internship will be primarily based at the Institut Pluridisciplinaire Hubert Curien in Strasbourg (supervisors: F Criscuolo, F Bertile, VA Viblanc), but the candidate will perform all laboratory work at Cell Environment, Genopole Evry in Paris (supervisor: R M’Kacher).
Depending on the motivation and quality of the candidate and the adequation with the supervising team, the internship may lead-on to a PhD. No fieldwork is planned within the context of this Masters proposal, but will be in the context of a PhD.
Required skills:
• Previous experience with laboratory techniques
• Good background in cellular and molecular biology and evolutionary biology
• Good level of English
• An interest in labwork and fieldwork
Acquired skills:
• Proficient learning of state-of-the-art laboratory techniques (cytogenetic preparations, fluorescence in situ hybridization)
• Advanced statistical skills (multivariate variance partitioning, random effects analyses)
• Scientific writing and presenting
Reading:
• Viblanc VA, Criscuolo F, et al. 2022. Telomere dynamics in a mammal: recovery after hibernation and loss after reproduction. Oecologia, 199: 301-312
• M’Kacher R, Colicchio B, et al. 2020. Telomere and centromere staining followed by M-FISH improves diagnosis of chromosomal instability and its clinical utility. Genes 11: 475.
Contact: If interested, please send full CV and cover letter to Vincent Viblanc (vincent.viblanc@iphc.cnrs.fr) before 15/10/24
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