Opportunities

Internship opportunities for Masters students

We regularly host first- and second-year masters students. If you are interested in evolution, cellular biology, genomics, nematodes, or  any combination thereof (!), please send a CV and cover letter to Marie Delattre:

marie.delattre@ens-lyon.fr
00 33 4 72 72 89 30

This year, we are particularly interested in recruiting interns to work on our 'Programmed DNA Elimination' (PDE) project - but other projects can also be defined. The PDE project is outlined below:

Why (and how) do some animal species systematically eliminate portions of their genome in their soma?

Some species systematically undergo excision and elimination of portions of their genome in somatic cells, in a process called programmed-DNA elimination (PDE) (while the germline cells maintain an intact genome). PDE has emerged multiple times throughout evolution. It has been extensively studied in unicellular Ciliates, which led to breakthrough discoveries on the role of smallRNAs in genome stability (1). In animals, although spotted for the first time in 1887, we still don’t know how the genome is scanned and excised at specific locations and what is the ultimate function and PDE (2). We fortuitously discovered PDE in the free-living nematodes Mesorhabitis (3, 4). In contrast to the other animal species so far described, Mesorhabditis are genetically tractable. This offers a unique opportunity to, at last, understand the mechanism, the role and the evolution of PDE.

We use a combination of comparative genomics, comparative cell biology and CRISPR/Cas9-based genetics to investigate:
1) the molecular machinery responsible for chromosome breakage and fragmentation: we recently identified a specific motif near breakpoints in one species and are now looking for the protein(s) that are recruited at this motif to generate double-strand breaks. For this, we generate CRISPR-Cas9 mutants for in vivo analysis and also use in vitro assays with extracts to purify the enzyme(s).
2) the evolution of PDE: we have now a large collection of nematode species with or without PDE. We perform comparative genomics (based on Hi-C and long read Pacbio sequencing) to identify for instance if all species rely on the same motif for elimination and if the same kinds of sequences are eliminated.

Techniques used:
The project can be oriented towards bench work, bioinformatics, or a combination of the two, depending on the profile and interest of the applicant.
-Dry lab: Handling 3rd generation (PacBio, Nanopore) and Hi-C sequencing data; genome assembly & annotation; comparative transcriptomics; bioinformatic scripting.
-Wet lab: CRISPR-Cas9 genetics, cytology and high resolution microscopy (single molecule FISH and DNA-FISH, expansion microscopy), biochemistry (DNA pull-down, Co-IP, chromatin-IP)

References (*from the lab)
1. I. Rzeszutek, X. X. Maurer-Alcalá, M. Nowacki, Programmed genome rearrangements in ciliates. Cell. Mol. Life Sci. CMLS. 77, 4615–4629 (2020).
2. J. Wang, R. E. Davis, Programmed DNA elimination in multicellular organisms. Curr. Opin. Genet. Dev. 27, 26–34 (2014).
3. *C. Rey, C. Launay, E. Wenger, M. Delattre, bioRxiv, doi:10.1101/2022.03.19.484980. Under revision @ Current Biology
4. *M. Grosmaire, C. Launay, M. Siegwald, T. Brugière, L. Estrada-Virrueta, D. Berger, C. Burny, L. Modolo, M. Blaxter, P. Meister, M.-A. Félix, P.-H. Gouyon, M. Delattre, Males as somatic investment in a parthenogenetic nematode. Science. 363, 1210–1213 (2019).