Description du sujet de thèse

The Tubulin Code team works on post-translational modifications (PTMs) of tubulins that modulate microtubules properties. The team seeks to characterize the enzymes that generate these PTMs and to understand the physiological role of these modifications using different models such as human cells in culture, mice and Drosophila. As such, the team has recently identified new enzymes modifying microtubules and a new PTM of β-tubulin in humans(1).
The aim of this thesis project is to characterize the enzyme responsible for and the role of α-tubulin detyrosination during gametogenesis in Drosophila. Detyrosination is an evolutionarily conserved PTM modulating microtubule dynamics and stability. It consists in the removal of the last amino acid from α-tubulin C-terminal tail which is exposed at microtubule surface. Two families of detyrosinases have been identified in mammals(1–4), but none of them is conserved in flies. We recently identified the enzyme generating α-tubulin detyrosination during spermatogenesis in Drosophila, which represents a third class of detyrosinating enzymes. The first objective of this project is to characterize the role of detyrosination during spermatogenesis using a mutant of the Drosophila enzyme that we have generated in the lab.
The second part of the PhD project is to investigate α-tubulin processing during Drosophila oogenesis. This part of the project is being carried out in collaboration with Antoine Guichet's group in the Institut Jacques Monod (Paris). Our aim is to identify additional enzyme responsible for another PTM of microtubules during oogenesis using biochemistry and genetic screening.
We are looking for a highly motivated candidate with a solid background in genetics and cellular biology. Experience with the Drosophila model is a plus. Main techniques involved for the project are: molecular and cellular biology, biochemistry, in vitro assays, imaging (including expansion microscopy and high-resolution imaging) and Drosophila genetics.

Bibliography :
1. Nicot, S. et al. A family of carboxypeptidases catalyzing α- and β-tubulin tail processing and deglutamylation. Sci. Adv. 9, (2023).
2. Aillaud, C. et al. Vasohibins/SVBP are tubulin carboxypeptidases (TCPs) that regulate neuron differentiation. Science 358, 1448–1453 (2017).
3. Landskron, L. et al. Posttranslational modification of microtubules by the MATCAP detyrosinase. Science 376, eabn6020 (2022).
4. Nieuwenhuis, J. et al. Vasohibins encode tubulin detyrosinating activity. Science 358, 1453–1456 (2017).

Contexte de travail

The Tubulin Code team is part of the Institut de Génétique Humaine (IGH), a CNRS - Université de Montpellier joint research unit (UMR 9002) dedicated to excellence in fundamental research and the study of pathologies. The IGH's main areas of research are genome dynamics, developmental genetics, epigenetics and molecular and cellular pathology. The Institute benefits from an excellent scientific environment in Montpellier, including numerous technical platforms. We have state-of-the-art equipment, particularly for microscopy.
See www.igh.cnrs.fr/ for more details.

The progress of the thesis is evaluated annually by a Comité de Suivi Individuel (CSI).

The IGH is located on the Arnaud de Villeneuve campus, which is part of the Objectif Employeur Pro-Vélo programme.

Contraintes et risques

Sometimes a few hours' work at the weekend.

Informations complémentaires

Expected skills
- Training in molecular, cellular and genetic biology
- Practical experience with the Drosophila model
- Cell culture
- Oral and written communication skills in English
- Ability to work in a multidisciplinary team
- Organizational skills
- Autonomy, rigor, creativity
- Keeping laboratory notebooks