Description of the thesis topic

Development of improved cross-linking mass spectrometry workflows to decipher protein-nucleic acid interactions

Objectives of the thesis: The objective of this PhD will be to develop structural mass spectrometry methods, mainly based on native mass spectrometry (nMS) and cross-linking (XL-MS), for the characterization of protein/protein or protein/nucleic acid complexes involved in co-transcriptional mRNA splicing events.
As part of the ANR COTRANSPLICE project, the candidate will develop sensitive and robust proteomic analytical workflows based on MS for chemical cross-linking of proteins/proteins, as well as proteins/nucleic acids. This will involve the development of new LC-MS/MS methods to improve the enrichment, separation, and identification of conjugated peptides in vitro and in vivo. This thesis work will allow the PhD student to use state-of-the-art mass spectrometry instruments (Eclipse Tribrid Orbitrap, TimsTOF, ASTRAL).
These workflows will then be applied to biological complexes and subcomplexes involved in co-transcriptional splicing, provided by our biologist collaborators, in order to obtain a more exhaustive and complete characterization of their role in biological processes.

Work Context

The Institut Pluridisciplinaire Hubert CURIEN (IPHC), a joint research unit under the joint supervision of CNRS and the University of Strasbourg (UMR7178), is a multidisciplinary laboratory where research teams from different scientific cultures (ecology, physiology and ethology, chemistry and subatomic physics) develop very high level programs based on scientific instrumentation. The IPHC is structured into 4 departments and has a total staff of 393 staff including 257 permanent staff (ie 119 researchers and teachers / researchers and 138 engineers and technicians), 46 staff on fixed-term contracts and 102 doctoral students.
The PhD student will join the "Laboratoire de Spectrométrie de Masse Bio-Organique" (LSMBO) team of the IPHC and will be able to benefit from all the material conditions (LC-MS / MS instrumentation), human support (sharing of expertise) and IT (access to all the software tools for the processing of LC-MS / MS data) necessary for the successful completion of this thesis project.

The expected skills are :
- hold a master's degree in analytical science
- solid knowledge of protein biochemistry of proteins, nucleic acids, mass spectrometry and chomatography
- experience in mass spectrometry and chomatography. Experience in proteomics andr XL-MS will be a strong advantage.
- fluency in English in writing and orally (at level B2 according to the Common European Framework of Reference for Languages) in order to be able to write results reports and present them at meetings and conferences.
- The multidisciplinary and collaborative context of this project requires that the candidate has a strong motivation, curiosity to expand his area of expertise, autonomy and ability to work in a team with strong constraints to meet deadlines.
The candidate must hold a master's and/or engineering degree.
He/she will need to prove a solid knowledge of (bio-)informatics data analysis and programming languages (notably Python), and will need to have some prior experience with the application of machine learning or AI methods. A strong interest in biology and/or biochemistry will be an advantage.
The candidate must have a good command of written and spoken English (at level B2 according to the Common European Framework of Reference for Languages) to be able to report regularly and present his/her results to the collaborators and at conferences.

The candidate will benefit from access to an administrative restaurant, partial reimbursement of travel expenses, a works council, the possibility of teleworking and training to adapt to the job.

Applications should include a detailed CV, a letter of motivation, a summary of the Master's thesis, as well as the grades of Master 1 and 2.

The position is located in a sector under the protection of scientific and technical potential (PPST), and therefore requires, in accordance with the regulations, that your arrival is authorized by the competent authority of the MESR.

Constraints and risks

- Casual work in staggered schedule
- Work in an ISO 9001 certified environment