Description of the thesis topic

Selenium (Se) is an essential trace element for life, thanks to its antioxidant properties via selenized amino acids and selenoproteins. In aquaculture, the Se-rich fishmeal used to feed farmed fish is being replaced by feed based on sustainable ingredients such as fish by-products that have until now been thrown away. Rich in Se, tuna by-products are highly attractive and innovative, but they can contain metallic contaminants such as mercury (Hg), which is toxic and can interact with Se to modify the expression of selenoproteins in breeding fish, reducing the transfer of nutrients to offspring. Because early-stage fry are particularly sensitive to oxidative stress, which makes them vulnerable to further development, studying Se metabolism in early-stage fry in relation to new diets is a key issue. To determine the chemical forms of Se and the interactions of Hg with surrounding biomolecules in such small size fry, direct analysis using multimodal imaging mass spectrometry must be developed.

The candidate will be in charge of analytical developments based on Laser Ablation coupled with ICPMS (LA-ICP MS) for quantitative imaging of total Se and Hg as well as selenoproteins after labelling by immunohistochemistry on fry thin sections. He will be involved in the development of sample preparation and analysis protocols for multimodal imaging of Se and Hg in fry thin sections. For multimodal imaging, the aim is to develop an original approach for combining MALDI mass spectrometry imaging with LA-ICP MS imaging, as well as with immunohistochemistry (IHC). Based on the benefits of each modalities, the idea is to be able to correlate i) molecular data (peptides/proteins) with elemental data, and ii) molecular data with cell typing. Advanced data processing is essential to extract and correlate imaging data from these three modalities.

These fundamental developments will be applied to identify the chemical forms of Se and Hg in fry sections following 5 different new sustainable diets.

Work Context

The Institut des sciences analytiques et de physico-chimie pour l'environnement et les matériaux (IPREM) is a joint research unit of the CNRS and the Université de Pau et des pays de l'Adour. The researchers of IPREM's three research clusters (CAPT, CME, PCM) are interested in developing fundamental knowledge in physical chemistry, analytical chemistry and microbiology, in relation to applications concerning the structure of living organisms, environmental management and the functional properties of different classes of materials. IPREM brings together expertise in analytical chemistry, organic synthesis, polymers and theoretical modelling, together with a state-of-the-art instrumental platform supported by UPPATech and the CNRS. A significant proportion of IPREM's members (CAPT and CME divisions) contribute to research into metals (isotopy, microanalysis, nano-imaging, speciation and metallomics).
This PhD thesis project is part of the ANR MOONFISH project and is linked with the CAPT (Analytical, Physical and Theoretical Chemistry) cluster, whose methodological developments are at the core of the research for the analysis of chemical elements (metals, metalloids, halogens) at trace level. The analytical methodologies developed include sample preparation protocols and the coupling of separation techniques (chromatography, electrophoresis) with elemental and molecular mass spectrometry (ICP MS and ESI-FT-MS/MS) and imaging techniques (LA-ICP MS, SIMS, MALDI-FT ICRMS).
This PhD project will be carried out in close collaboration with the CBMN in Bordeaux for developments of multimodal imaging with MALDI mass spectrometry.
The candidate will also interact with researchers at NUMEA (St-Pée sur Nivelle (64)) for the development of the immunohistochemistry protocol.
The candidate will be registered at the ED SEA 211 doctoral school at the Université de Pau et des pays de l'Adour (https://ed-sea.univ-pau.fr).

Constraints and risks

The candidate will be required to travel to the CBMN for periods of 1 month to 1.5 months for MALDI-Orbitrap MS analyses.

Additional Information

The candidate will have a Master 2 in chemistry with a strong analytical chemistry component. Solid theoretical and practical knowledge of mass spectrometry is required. Knowledge of biology would be appreciated. Candidates must have a good level of English, the ability to work both in a team and autonomously, and the ability to summarize and present his/her research work.

To apply, candidates must provide:
- a CV and a single pdf document containing the following items:
- a letter of motivation briefly outlining the applicant's research interests, particularly for this PhD topic.
- marks and diplomas attesting to completion of the bachelor's and master's degrees
- an approved document proving proficiency in English
- the names and contact details of two referees. One of these must be the principal supervisor of the master's thesis
- if applicable, a list of all scientific works/publications. (Do not include full papers).