towards An Artificial Intelligence Approach for - Nancy, France - Centre National de la Recherche Scientifique

Description

Réf
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ABG-113210

• Sujet de Thèse 12/04/2023
• Contrat doctoral
• Centre National de la Recherche Scientifique
• Lieu de travail
• Nancy
• Grand Est
• France
• Intitulé du sujet
• Champs scientifiques
• Biochimie
• Biotechnologie
• Chimie
• Mots clés peptides, enzymatic hydrolysis of proteins, screening, metalchelating peptides, coordination chemistry, emulsions

Description du sujet:


Modalities of supervision, follow-up of the training and progress of the doctoral student's research.

• This thesis attached to the doctoral school SIMPPE of the Université de Lorraine (UL) will be directed by Laetitia Canabady-Rochelle (CNRS Research scientist, HDR, attached to LRGP, UMR 7274 CNRS-UL) and codirected by Katalin Selmeczi (Associate Professor, UL, HDR, attached to L2CM, UMR 7053 CNRS-UL). It also involves other UL scientists, notably Roda Bounaceur (LRGP, IR developing the computer code) and Cédric Paris (IR, PASM platform manager). An international mobility of 4 to 6 months is planned in the team of Professor Charlotte Jacobsen (Danish Technological University, DTU, Denmark) in order to study the capacity of metal complexing peptides to inhibit lipid oxidation in emulsions. The student will carry out his thesis between these two laboratories and some of his experiments will be carried out on stateoftheart equipment present on the platforms of the University of Lorraine (PASM, ASIA, B2S, PhotoNS). Regular followups will be made with his/her supervisors. An individual followup committee of the PhD thesis will be carried out each year. _in silico_ from various theoretical proteins sequences, submitted to various theoretical hydrolysis treatment and complexation rules. In this context, the aim of this PhD thesis is to validate experimentally the construction of this internal software enabling the theoretical screening of MCPs in hydrolysate and enrich it in various enzymatic and complexation rules.

Themes:

Proteolysis, peptide hydrolysate, peptide, metal complexation, screening, SPR, mass spectrometry


Field:

Biochemistry of proteins and peptides, biotechnology, coordination chemistry, physicochemical analysis.
Context.

In a context of ecological transition linked to the bioeconomy, it is essential to discover new biomolecules while exploiting and valorizing the co-products generated by the agro-food industries.

The cakes co-generated during oil production are rich in proteins (~30% by mass).

Commonly used for animal feed, the proteins contained in these co-products could be extracted and valorized after proteolysis for the bio-functional peptides they contain.

Indeed, the presence of such target peptides has been reported in protein hydrolysates for their antioxidant, antihypertensive or antimicrobial properties (1,2).

Among the functional properties, some studies have highlighted the presence of metal-chelating peptides (MCP) in protein hydrolysates (3, 4).

However, depending on the nature of the complexed metal ion, MCPs may have different bioactivities beneficial for nutraceuticals, cosmetics or health (5).

For example, by complexing iron and copper, PCMs could inhibit lipid oxidation in emulsion systems and serve as an alternative to EDTA-type preservative (6).
Objectives.

The objective of this thesis is (i) to continue the development of an in-house software for in-silico screening of metal complexing peptides with the help of a computer scientist and (ii) to validate its performances by various experiments (proteolysis, SPR screening, mass spectrometry, IMAC separation), to guide the experimental approach for the screening/separation/identification of metal-complexing peptides in various protein resources (performed at UL, France) and (iii) to evaluate their ability to inhibit lipid oxidation in emulsions (DTU partnership, Denmark).
Method. After a first step of bibliography, allowing to define the rules of proteolysis and complexation of metals, these will be coded in a specific software under construction in the French laboratory.

This software, built with the help of a computer scientist, will allow the in-silico screening of metal complexing peptides.

In a second step, these theoretical results obtained via this software will have to be validated using various experiments of proteolysis (different sources of proteins and proteolytic enzymes), screening (optical techniques by SPR and SwithSENSE, mass spectrometry, study of complexation by spectroscopy) and separation (affinity chromatography of IMAC type).

These validation experiments will be carried out both on peptide hydrolysates but also on synthetic peptides to have a more detailed knowledge of the complexation phenomena.

In a third phase of the project, the most promising metal complexing peptides will be evaluated for their ability to inhibit lipid oxidation in emulsions, during an international mobility carried out at DTU.

-**Scientific, material (specific security conditions) and financial conditions of the rese