Deubiquitinases (DUBs) are specific proteases which remove ubiquitin moieties from ubiquitinated proteins. DUBs regulate many biological functions including protein stability, cell signaling or endocytosis. Their dysregulation has been linked to many human pathologies, enlightening the importance of understanding how their functions are coordinated and regulated. Our team has been studying the DUB USP36 in the model organism Drosophila melanogaster for several years. dUSP36 is involved in several physiological processes including immunity, stem cell maintenance, autophagy. Moreover, we have recently shown that a nucleolar isoform of dUSP36 promotes cell growth and proliferation by regulating the Drosophila homolog of the MYC oncogenic protein. The MYC-USP36 complex, which also includes the E3 ligases AGO represents an evolutionary conserved regulatory node that tightly controls MYC ubiquitination levels and stability in both Drosophila and human cells. To further understand USP36 functions in vivo, we have generated a catalytically inactive version of the endogenous dUSP36 protein by mutating by CRISPR-Cas9 its catalytic cysteine to a serine residue. Compared to Drosophila Usp36 null mutants, which produce no dUSP36 protein and display strong cell growth defects leading to larval lethality, Usp36 catalytic dead mutants display very mild cell growth defects and survive to adulthood. This preliminary result unambiguously shows that the catalytic dead version of dUSP36 can fulfil some of the functions of the wild-type protein. This completely reshapes our understanding of the mechanisms by which USP36 regulates MYC stability. Genetic and biochemical experiments will be carried out to characterize MYC ubiquitination status and the activity of the E3 ligase AGO. Additionally, the requirement of USP36 catalytic activity in the other known phenotypes of Usp36 mutants (immunity, stem cell maintenance and autophagy) will be addressed using experimental procedures (RT q- PCR and immunofluorescence) which are routinely used in the team.

Keywords
MYC-dependent cell growth, ubiquitin.

Supervisor

Call for students applications. Academic year 2021-2022

In the framework of the Chemistry Biology Health (CBH) Graduate School of Université Grenoble Alpes, the GRAL research programme funds MSc (Master 2) research scholarships.

We seek motivated candidates planning to:

attend one of the following Master programmes (2^nd year MSc / Master 2 / M2) at Université Grenoble Alpes (taught in English):
Master in Biology:
Structural Biology of Pathogens
Immunology, Microbiology, Infectious Diseases
Neurobiology, Neurosciences
Physiology, Epigenetics Development, Cell Differentiation

Master in Plant Biology:
PLANTA International

& do a research internship in Integrated & Structural Cell Biology at one of the labs associated with the GRAL programme in Grenoble: IBS, PCV, BS, and CBM.

A maximum of 6 GRAL scholarships of 8 000 € are offered to cover the academic year from September 2021 to June 2022, which includes 4 months of courses and 6 months of research internship.

The call is open to EU and non-EU students.

The candidates must send their application in a unique pdf file to anne-mathilde.thierry _at_ ibs.fr (e-mail subject: M2-2021-LastName) before May 14^th 2021 (23:59, CET), including:

A cover letter indicating the selected MSc programme at Université Grenoble Alpes, and 2 choices (ranked) for the 6-month research internship project
A CV
Diplomas and copies of academic transcripts for the last 2 academic years (translated to French or English if appropriate)
For non-native English speakers, level of language proficiency (e.g. TOEIC, Bulats, etc.)
One letter of recommendation
E-candidate portal application number

We strongly recommend that the candidates take contact with the potential supervisor(s) for the research project(s) of interest.

The applications will be evaluated by a selection committee composed of representatives of the GRAL Directory and the Master programmes.

The scholarship is conditional to the registration to one of the above programmes of the master’s degree in Biology of Université Grenoble Alpes, and to the recipient maintaining a satisfactory academic record in the programme. The admission to a 2^nd year MSc programme (M2) at Université Grenoble Alpes is fully independent of the GRAL Scholarship. Application deadlines may differ between the different programmes. See admission requirements on Université Grenoble Alpes’s website: http://www.univ-grenoble-alpes.fr/fr/grandes-missions/formation/candidatures-et-inscriptions/

Schedule

Opening of the call for applications: March 1^st 2021
Applications must be submitted by May 14^th 2021
Results: June 2021