Edsmre.univ-lille1.fr

DOCTORAL SCHOOL “ MATERIALS, RADIATION AND
ENVIRONMENTAL SCIENCES ” (ED 104)
UNIVERSITY : Lille 1
PhD. programme : Biological functions engineering
Title of the thesis: Understanding of the food proteins digestion mechanisms by the development of
an in vitro simulated digestion process and by the study of the generated peptide biological
activities.

Supervisor(s):

Laboratory : ProBioGEM
Research project (international/national/regional):

Scientific background

For a long time, the digestion has been considered as a “black box” transforming food into unitary compounds such as amino acids needed for metabolism and in the same way, the only function of the protein hydrolysis was to lead to amino acid assimilation. In recent years, many studies have shown the importance of peptides generated during digestion which could be involved in many physiological functions. In this context the objective of this project is to generate knowledge on the mechanisms of in vivo proteins digestion by the development of an in vitro simulated digestion including the three compartments that are the mouth, the stomach and the gut. The strategy is based on the use of the peptide mapping obtained from the hydrolysis of selected food proteins, well known in the laboratory (hemoglobin / pepsin or RuBisCO / pepsin) in order to identify the
peptides generated during the simulated digestion process. The studied biological activities will be the anti-
hypertensive molecules and the peptides able to stimulate the secretion of gut hormones involved in the
food intake regulation. The identification of biologically active substances from food by-products is an
important challenge in the production of novel peptides derived agents of interest for nutraceutic and
pharmaceutic markets.

In one hand, the goal of this work will be to understand the mechanisms of the gastro-intestinal digestive process of proteins that lead to the secretion of gut hormones able to regulate food intake. Many studies have shown the potential of peptides involved in the stimulation of the secretion of these hormones, which are mainly cholecystokinins (CCK), Glucagon Like Peptide-1 (GLP-1) and peptide YY (PYY) for the treatment and prevention of diseases such as obesity or elderly malnutrition. On the other hand this work will focus on peptides generated during the gastro-intestinal digestion and able to exert an anti-hypertensive effect by their ability to inhibit the angiotensin converting enzyme
(ACE). Inhibition of ACE is a pharmacological strategy commonly used to regulate blood pressure in
hypertensive patients (eg drug: captopril).
Research objectives:
(1)
follow the changes of the selected proteins of an experimental process simulating, in vitro, the different compartments of the digestion; (2) understand the mechanisms of action of the intermediate peptides generated during digestion which leads to stimulation of the secretion of CCK, GLP-1 and PYY through the use of intestinal cell lines; (3) characterize the in vitro and in vivo activity (agonist or antagonist) of the searched peptides through the use of cellular and animal models(rat, pig); (4) identify and purify these active molecules in order to improve the understanding of the biological mechanisms, but also to complete the existing databases dedicated to in silico prediction of biological activities (in relation with the bioinformatic platform of the laboratory). Some of these experiments will be conducted in collaboration, both in the laboratory but also with others laboratories, and will allow the candidate to experiment many techniques and acquire knowledge in various fields ranging from enzyme engineering to in vivo experimentation through cell culture and proteomics.

Source: http://edsmre.univ-lille1.fr/uploads/media/Eng-ProBioGEM-Ravallec-2012.pdf