M2-Msc_Internship_offer_DNAOrigami_2027
Supervisors: Dr X. Guillory (PI), C. Walter (PhD);
Remuneration: 580€ net/month;
Duration: 6 months between January and July 2027
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).
• Structural characterization of protein-DNA conjugates (AFM, CryoEM).
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.
Please send CV, cover letter, M1/4th year transcripts and at least one contact likely to provide a recommendation to: Dr. Xavier Guillory – xavier.guillory@univ-rennes.fr & Chloé Walter chloe.walter@etudiant.univ-rennes.fr
DEADLINE – 18th September 2026
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.