Job offer

Biological sciences » Biological engineering

Organisation/Company: INSERM U1212-CNRS UMR 5320

Research Field: Chemistry » Biochemistry, Biological sciences » Biological engineering

Researcher Profile: Recognised Researcher (R2), Leading Researcher (R4), First Stage Researcher (R1), Established Researcher (R3)

Country: France

Application Deadline: 1 Jun 2025 - 22:00 (UTC)

Type of Contract: Temporary

Job Status: Full-time

Offer Starting Date: 1 Sep 2025

Is the job funded through the EU Research Framework Programme? Not funded by a EU programme

Is the Job related to staff position within a Research Infrastructure? No

Offer Description

Specific mRNA splicing correction using small molecules is an emerging field of drug discovery which has already provided innovative therapeutic applications in the context of inherited diseases. In the context of Spinal Muscular Atrophy (Naryshkin NA., Science 2014) and Huntington’s disease (Bhattacharyya A., Nat. Comm. 2021), the small molecule acts as a molecular glue between the first particle of the spliceosome and an A-1 bulged 5’-splice site to promote specific splicing correction. Even if the mechanism of action of the first small molecule splicing modifiers was elucidated (Campagne S. et al., Nat. Chem. Biol. 2019; Malard F. et al., Nucleic Acids Research 2024) and the concept of 5’-splice site bulge repair was discovered, there are still some open questions to fully understand the gene selectivity of splicing modifiers targeting an A-1 bulged 5’-splice site (Ishigami Y. et al., Nature Comm. 2024).

We are looking for a motivated PhD candidate to decipher the molecular details of small molecules RNA interactions in the context of specific splicing correction. During this part of the PhD thesis, the candidate will determine the structure of already known small molecule splicing modifiers bound to specific RNA helices and will investigate the effect of divalent ions on these interactions. Known small molecule splicing modifiers are active on A-1 bulged 5’-splice sites and brought novel therapeutic solutions in the context of Spinal Muscular Atrophy and Huntington’s diseases. However, mutations at the position -1 into C or U also trigger human diseases. In this context, the PhD candidate will also participate in the group project aiming at diversifying the pool of small molecule splicing modifiers and will discover using state-of-the-art AI-powered methods novel splicing modifiers acting on U-1 and C-1 bulged 5’-splice sites. Since many diseases originate from mutations falling at the position -1 of the 5’-splice sites, the overall aim of the project is to further explore the fundamental basis of the small molecule splicing modifier gene specificity but also to rationally design new tools for biomedicine. This PhD project is funded by the ANR EpiCor (to S.C. and JM.C.) and the expected starting date is in Autumn 2025.

We are seeking an excellent student who is willing to work at the interface between chemistry, biochemistry, drug discovery, genetics, and structural biology in a young and dynamic group of research. Previous experience in structural biology, genetics, or bioinformatics will be a nice add-on.