L’Inserm est le seul organisme public français entièrement dédié à la recherche biologique, médicale et en santé des populations. Il dispose de laboratoires de recherche sur l’ensemble du territoire, regroupés en 12 Délégations Régionales. Notre institut réunit 15 000 chercheurs, ingénieurs, techniciens et personnels administratifs, avec un objectif commun : améliorer la santé de tous par le progrès des connaissances sur le vivant et sur les maladies, l’innovation dans les traitements et la recherche en santé publique.

Rejoindre l’Inserm, c’est intégrer un institut engagé pour la parité et l’égalité professionnelle, la diversité et l’accompagnement de ses agents en situation de handicap, dès le recrutement et tout au long de la carrière. Afin de préserver le bien-être au travail, l’Inserm mène une politique active en matière de conditions de travail, reposant notamment sur un juste équilibre entre vie personnelle et vie professionnelle.

L'Inserm a reçu en 2016 le label européen HR Excellence in Research et s'est engagé à faire évoluer ses pratiques de recrutement et d'évaluation des chercheurs.

Internship in Chemical Biology

DNA scaffolds for tunable spatiotemporal control over receptor kinase assemblies.

Scientific background – Cellular stress induced by the abnormal accumulation of improperly folded proteins in the endoplasmic reticulum (ER) is emerging as a major actor in disease development and an appealing actionable target.[1] ER stress levels are under constant surveillance by the unfolded protein response (UPR), a major adaptive mechanism that lies at the core of cellular homeostasis and is responsible for cellular life-or-death decisions. The Inositol-requiring enzyme 1 (IRE1), the most evolutionary conserved UPR transducer, is an ER-resident transmembrane protein with a cytosolic dual kinase/RNase activity controlling pro-survival or pro-death signals. Yet, despite >20 years of investigations, the precise molecular mechanisms by which IRE1 is activated and exerts its catalytic and scaffolding functions still remain unclear and a subject of debate.[2] The group aims at deciphering the molecular mechanisms of IRE1 activation through a unique and novel prism at the interface of chemical biology, supramolecular chemistry and structural biology.

Description of the project & duties - This internship is in support of a PhD project focusing on using a programmable synthetic platform made of DNA structures (i.e. DNA origami) to control the nanoscale organization and nature of different complexes of a kinase protein.[3]

As part of this internship, you will focus on:

1 –Expressing, purifying and functionalizing the protein kinase N-terminus using a small molecule reagent.

2 - Assembling and purifying DNA origami structures.

3 - Bioconjugating proteins on the DNA origami using DNA hybridization principles.

4- Validating by AFM microscopy the functionalized Protein-DNA nanostructure obtained.

5 – Evaluating the enzymatic activities of the protein using established biochemical assays and molecular biology techniques.

Main activities and techniques involved –

• Molecular biology (design and conception of plasmids).

• Protein expression in eukaryotic cells.

• Protein engineering, bioconjugation, purification (affinity & SEC chromatography).

• Enzymatic assays.

• Structural characterization of protein-DNA conjugates (AFM, CryoEM).

References: [1] iScience 2023, 106687. https://doi.org/10.1016/j.isci.2023.106687; [2] Biomedicines 9, 156. https://doi.org/10.3390/biomedicines9020156; [3] Nat. Catal. 2020, 3, 295–306. https://doi.org/10.1038/s41929-019-0403-7.

Applicant profile – We encourage applications from highly motivated students from the national and international community with a background in chemical biology, biochemistry, biophysics, molecular biology, or other life sciences and with outstanding qualifications. Application only on this platform.