PhD Student (M/F) in Molecular Biology for the Development of Inhibitory Aptamers and Detection of Matrix Metalloproteinases.

Descrizione

PhD Student (M/F) in Molecular Biology for the Development of Inhibitory Aptamers and Detection of Matrix Metalloproteinases. Sintesi in italiano (traduzione automatica): Il lavoro di dottorato si svolgerà nel team 'Digital RNA Biology' presso l'unità CNRS 'Architecture et Réactivité de l'ARN' a Strasburgo. Il candidato si concentrerà sullo sviluppo di aptameri inibitori e sulla rilevazione delle metalloproteinasi della matrice, in particolare MMP12, attraverso approcci di selezione in vitro (SELEX). Il progetto prevede l'uso di microfluidica a goccia e sequenziamento ad alta capacità per studiare le funzioni di MMP12. È richiesta una laurea in Biologia o un campo correlato. Il dottorando avrà accesso a tutte le attrezzature necessarie e parteciperà a riunioni di supervisione regolari. Il laboratorio è ben collegato ai mezzi pubblici e offre un ambiente di lavoro flessibile. The PhD work will be carried out in the "Digital RNA Biology" team led by Michael Ryckelynck, based within the CNRS unit "Architecture et Réactivité de l'ARN" (Institute of Molecular and Cellular Biology, Strasbourg). The team has unique, internationally recognized expertise in developing and using droplet microfluidics combined with high-throughput sequencing for RNA studies and the directed evolution of fluorescent RNA aptamers for biotechnological applications. The team currently consists of three permanent researchers, one postdoctoral fellow, five PhD students, and three engineers. The PhD student will have access to all the equipment and infrastructure necessary for the successful completion of the project. In addition to daily informal supervision and regular team laboratory meetings, weekly individual progress meetings will be organized with the thesis director. Several project follow-up meetings will also be held biannually within the consortium. Moreover, the laboratory is located in close proximity to public transportation (including the tram) as well as university eating facilities. Additionally, no specific time constraints (such as staggered hours or other obligations) will be required for carrying out the mission. For more information about the team and its activities, please visit the website: https://ibmc.cnrs.fr/en/laboratoire/arn-en/equipes/biologie-digitale-de… Matrix metalloproteinases (MMPs) are key players in tissue remodeling and the regulation of certain biological mechanisms. Among these enzymes, MMP12, produced and secreted by macrophages, is particularly interesting due to its multiple roles. In addition to its canonical function as a secreted protease mediating the degradation of the extracellular matrix and certain cell surface receptors, MMP12 also exhibits several non-canonical "moonlighting" functions. Notably, the catalytic domain of the protein has been shown to regulate the expression of genes in the NF-κB pathway (involved in inflammation, among other processes) by directly binding to nuclear DNA. Furthermore, the free hemopexin-like domain of MMP12 has been demonstrated to possess antibacterial properties within lysosomes. Thus, not only the full MMP12 protein but also its individual domains exhibit varied functions depending on their state and localization. This PhD project aims to deepen our understanding of the MMP12 system and dissect its complexities in greater detail through the development of new tools dedicated to imaging and/or targeted functional interference. The main objective of the PhD work will be the identification of aptamers (oligonucleotides capable of specifically recognizing epitopes on proteins, analogous to antibodies) targeting the different domains of the protein (catalytic domain, hemopexin-like domain, either isolated or in combination). To achieve this, the candidate will use in vitro selection approaches (SELEX) to enrich large libraries of candidate oligonucleotides with molecules capable of specifically binding the target protein (or domain). The enriched libraries obtained will then be screened using high-throughput droplet microfluidics platforms developed by the team. This dual approach will enable the rapid and efficient isolation of two types of aptamers: i) Aptamers dedicated to imaging protein targets, achieved by coupling the aptamers to a fluorescent module developed by the team. ii) Inhibitory aptamers that, by strongly binding to the protein, will inhibit a targeted function (enzymatic activity, intracellular relocalization, DNA binding, depending on the intended function). The combined use of these new molecular tools will enable a more in-depth and precise study of MMP12 under cellular conditions. This doctoral project will be affiliated with the Doctoral School of Life and Health Sciences of Strasbourg (ED-414), which has validated it. Conducted in close collaboration with Laurent Devel's team (CEA), who will develop new chemical tools, this res Annuncio in inglese. Fonte: Euraxess (Commissione europea).