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Subject of the Master's internship

Bio-orthogonal chemistry to study the trafficking of the Atox1 copper chaperone in mammalian cells

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Published on 26 March 2022
Project summary
The ability to specifically engineer a protein of interest in living cells offers a wide range of possible studies. A way that emerged within the last ten years is the use of bio-orthogonal chemistry strategies to incorporate a non-canonical amino acid (ncAA) at a specific position in the protein of interest. The development of cyclo- octyne ncAA enables the use of click chemistry to couple these ncAA to tetrazine-conjugated molecules such as fluorophores. Besides, this type of click chemistry reactions can be performed in vitro but also in living cells. In this master project, this strategy will be used to specifically fluorescently label Atox1. Atox1 is a small protein, crucial for copper (Cu) homeostasis in Human. Atox1 is a Cu chaperone that chelate Cu with high affinity upon its cellular entry. Cu-bound Atox1 traffics through the cell for delivery of Cu to target proteins. Since Cu is at the same time an element essential for life and heavily toxic for the cell in its free form, these trafficking processes are finely orchestrated and there is a need to better understand them. This goal will be achieved thanks to super resolution fluorescence microscopy. This imaging approach will enable to decipher Atox1 localization and dynamics in different conditions and at tens of nanometer resolution. This analysis will be performed in Cu normal, deprived and overloaded conditions to mimic different situations encountered by human cells in healthy and disease conditions. Besides, Atox1 has been shown to play a role in intracellular trafficking and excretion of platinum complexes used in cancer therapy. Therefore, the methodology developed in this project will enable to study this question. Finally, bio-orthogonal chemistry will be used to engineer Atox1 with a polarizing agent to explore a novel in cell NMR approach enabling to obtain molecular information within the cellular context.

Host laboratory
Met&Or team.

Bio-orthogonal chemistry, copper homeostasis, super resolution fluorescence microscopy.

Aurélien Deniaud

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 (2nd 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_ (e-mail subject: M2-2021-LastName) before May 14th 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
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 2nd 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:


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

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