Telomeres are repeated sequences found at the end of the linear chromosomes of most eukaryotes and are required for chromosome integrity. They shorten with each cell division and expression of the reverse transcriptase telomerase allows for de novo addition of telomeric repeats, counteracting telomere shortening. Although Chlamydomonas reinhardtii, a photosynthetic unicellular green alga, is widely used as a model organism in photosynthesis and flagella research, as well as for biotechnological applications, the biology of its telomeres has not been investigated in depth.
We have recently characterized telomere sequence, structure and length distribution in C. reinhardtii. We have also identified CrTERT, the gene encoding the catalytic subunit of telomerase and shown that mutants of this gene have telomeres that continuously shorten, demonstrating that telomerase is required for long-term maintenance of telomeres in C. reinhardtii.
Based on these initial results, the candidate will investigate the phenotypes of telomerase-negative mutants, including replicative senescence and telomerase-independent survival, and the molecular mechanisms of telomere maintenance in C. reinhardtii, notably with regards to environmental conditions, genotoxic stress, in mutants affected in core metabolic and physiological pathways (e.g. photosynthesis or respiration) and in available strains that display markedly different telomere length distributions. The candidate will also characterize new factors involved in telomere integrity and length regulation.
Context and funding:
The project will be performed in a newly created group headed by Zhou Xu (http://www.lcqb.upmc.fr/telomere-and-genome-stability), which is part of the Laboratory of Computational and Quantitative Biology (LCQB, http://www.lcqb.upmc.fr), at Sorbonne Université (Paris, France) and jointly supported by the University and the National Center for Scientific Research (CNRS). The group has broad scientific interests in telomere biology and DNA damage response both in S. cerevisiae and in C. reinhardtii, using single-cell approaches, molecular biology, biochemistry, genetics and mathematical modeling.
The postdoc position is funded for 2 years through a young researcher ANR (Agence National de la Recherche) grant awarded to the group and will start in early 2019.
The project is a close collaboration with Stephan Eberhard (Assistant Professor at Sorbonne Université, http://www.ibpc.fr/UMR7141/index.html), expert in C. reinhardtii physiology.
The candidate must have a PhD degree in Life Sciences and experience in the molecular genetics, biochemistry and molecular biology of the model organism C. reinhardtii will be an important asset of the candidate. The candidate must be proficient in English. To apply please send your CV, a cover letter describing your interests and previous work, and contact information of 2 references to Zhou Xu:
email@example.com ; firstname.lastname@example.org
Eberhard, S.,..., and Xu, Z. Molecular characterization of Chlamydomonas reinhardtii telomeres and telomerase mutants. In prep. (This manuscript will soon be submitted for publication and can be sent to the candidate upon request)
Coutelier H.*, Xu Z.*1 et al. Adaptation to DNA damage checkpoint in senescent telomerase-negative cells promotes genome instability. Genes Dev (2018). 1Corresponding authors, *co-first authors.
Xu, Z. et al. Two routes to senescence revealed by real-time analysis of telomerase-negative single lineages. Nat Commun 6, 7680, (2015).
Damodaran, S. P., Eberhard, S. et al. A Millifluidic Study of Cell-to-Cell Heterogeneity in Growth-Rate and Cell- Division Capability in Populations of Isogenic Cells of Chlamydomonas reinhardtii. PLoS One 10, e0118987, (2015).
Xu, Z. et al. The length of the shortest telomere as the major determinant of the onset of replicative senescence. Genetics 194, 847-857, (2013).