DC 11: Design, synthesis and biological evaluation of RNA ligands targeting the SAM-I/IV riboswitch

PhD project description:

The SAM-I/IV riboswitch belongs to a class of riboswitches that specifically binds to S-adenosylmethionine (SAM), a cofactor used in many kinds of methylation reactions. During the development of the project, in collaboration with DC12 and 13, we aim to perform the structure-based design of new ligands specific for this riboswitch using the available crystal structures and the structures determined in WP1 as well as taking advantage of the different analogues of SAM available in the literature for other scopes in addition to the hits discovered here. We will perform the synthesis of different series of RNA binders bearing suitable physico-chemical properties for prokaryote targeting and evaluate their affinity and selectivity using fluorescence-based biochemical assays available in the laboratory (the latter will also be done for other RNA targets). To determine selectivity, we will also measure ligand binding to tRNA and double stranded DNA. The biological evaluation of the most promising compounds in vitro will then be performed during secondments at MUAS and in collaboration with DC8 and DC9. We thus expect to obtain active compounds suitable for further lead optimization but also to increase our knowledge about RNA targeting and biological function thanks to these important chemical biology tools.

Research environment:

The PhD position is associated to Maria Duca, director of the research group for Targeting of Nucleic Acids.

Skills/qualifications:

• 5-years degree (Master) in Organic/Medicinal Chemistry, or related fields.
• Practical experience in organic and bio-organic chemistry.
• Good level of English proficiency (understood, spoken and written).
• Team spirit and proactive attitude.

We seek a person interested in medicinal chemistry and/or synthetic organic chemistry with an interest for biological applications. A solid knowledge in heteroaromatic chemistry as well as conjugation techniques is required.

Benefits/salary/social security:

• Becoming a Marie Skłodowska-Curie fellow
• Work on an innovative project of high societal value
• Be recruited in France under a full-time employment contract for a period of 36-months
• Have the opportunity to work in a laboratory abroad during secondment
• Earn an above-national standard salary including social security coverage, unemployment benefits and pension rights
• Form part of a rich multidisciplinary network of researchers and supervisors

The gross salary will be between 2700-2900 € with additional mobility allowance and family allowance if applicable.

The position is open to candidates of any nationality, as long as they fulfill the requirements set for the DCs funded by MSCA.
The period of employment is 36 months full time (100%). Starting date is approximately February 2025 (or according to mutual agreement). The position is a full-time position.

For more information about the position, please contact Maria Duca.