Postdoctoral position in molecular biology and human genomics (Nice, France)

Inserm, Niue

Updated: over 1 year ago
Job Type: FullTime
Deadline: 09 Oct 2022

Project overview - Retrotransposons make up to 50 % of the human genome but are often disregarded because their high copy number and variability pose unique technical challenges. However, while methods to study them are rapidly evolving, it becomes clear that they play a major role in the plasticity of the cancer genome and epigenome.

Retrotransposon replicate through a copy and paste mechanism. New insertions can disrupt genes and gene regulatory networks leading to genetic diseases and tumorigenesis. Pre-existing transposable elements can also be epigenetically reactivated, acting as new promoters and enhancers and leading to abnormal gene activities including overexpression of oncogenes. On the other hand, their transcriptional activity can produce cancer-specific products including immunogenic antigens and double stranded RNAs, which stimulate immune responses and create new vulnerabilities that can be exploited for cancer treatment. Of note, similar processes appear to be operating during cellular senescence and aging.

Remarkably, only few loci are capable of retrotransposition in vivo and these loci differ among cell types. To identify active loci, the selected candidate will develop massively parallel assays to measure genome-wide (i) the intrinsic transcriptional activity of retrotransposon promoters; (ii) their mobilization capabilities. Other projects ongoing in the lab, which could be also pursued by the selected candidate, focus (i) on the impact of retrotransposons on gene expression, or (ii) on understanding retrotransposon site selection in the human genome. Together, these projects will extend our knowledge of a potent endogenous mutagen in humans.

The project requires excellent molecular and cellular biology skills, a strong background and interest for genetics, genomics, and epigenetics, and a taste for technological developments. Although not absolutely required, bioinformatic skills related to next-generation sequencing data processing would be an asset.

Environment - The "Retrotransposon and genome stability" group, headed by Gael Cristofari, is one of the founding teams of the Institute for Research on Cancer and Aging of Nice (IRCAN), located at the Faculty of Medicine of the University Côte d'Azur. It is supported by two major supervising bodies, the National Center for Scientific Research (CNRS) and the French National Institute of Health and Medical Research (Inserm), as well as by the French Foundation for Medical Research (FRM) through an FRM team award. We have full access to cutting-edge core facilities (genomics, microscopy, cytometry, etc). We offer an international, friendly and dynamic environment. The working language is English.

How to apply? The candidate must have obtained a Ph.D. degree in Life Sciences and have a solid background and publication track in molecular and cellular biology, genomics, or genetics. We are expecting high motivation, and ability to work independently as well as part of the team. Good verbal and written communication skills in English are required. The earliest start date is November 2022, but a later start date is possible.

To apply, please send an email to Gael Cristofari ([email protected] ) indicating « postdoc application 2022 » in the object, with the following documents:

  • a CV (including a publication list and the information contacts for 2 to 3 referees)
  • a cover letter describing your previous work and why you are interested to work in our lab, your career goals, and a putative starting date.

Recent selected publications

  • Sarkar, A., et al. (2022). Targeted nanopore resequencing and methylation analysis of LINE-1 retrotransposons. BioRxiv 2022.06.25.497594. https://doi.org/10.1101/2022.06.25.497594 .

  • Lanciano, S., and Cristofari, G. (2022). Flip-flop genomics: Charting inversions in the human population. Cell 185, 1811–1813. https://doi.org/10.1016/j.cell.2022.05.002 .

  • Lanciano, S., and Cristofari, G. (2020). Measuring and interpreting transposable element expression. Nat Rev Genet 21, 721–736. https://doi.org/10.1038/s41576-020-0251-y .

  • Tristán-Ramos, P., et al. (2020). The tumor suppressor microRNA let-7 inhibits human LINE-1 retrotransposition. Nat Commun 11, 5712. https://doi.org/10.1038/s41467-020-19430-4 .

  • Sultana, T., et al. (2019). The Landscape of L1 Retrotransposons in the Human Genome Is Shaped by Pre-insertion Sequence Biases and Post-insertion Selection. Mol Cell 74, 555-570.e7. https://doi.org/10.1016/j.molcel.2019.02.036 .

  • Philippe, C., et al. (2016). Activation of individual L1 retrotransposon instances is restricted to cell-type dependent permissive loci. eLife 5, 166. https://doi.org/10.7554/elife.13926 .


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