Job offers

LIRIC provides a unique space and environment for research on inflammatory disease. Our teams welcome scientists, clinicians doctors, pharmacists, students, manufacturers and innovators in a very open structure that fosters creativity, promotes innovation and includes all types of skills.
You will find below our PhD program, internship and job offers.
If you would like to join us, please feel free to contact us.

Master 2 proposed in Team Dubuquoy (1)

Bioremédiation des métaux lourds par des microorganismes alimentaires naturels et des bactéries du microbiote intestinal

Tuteur : Benoît Foligné ; Lille Inflammation Research International Center (LIRIC) - UMR995, Université de Lille / Inserm / CHU de Lille. Faculté de Pharmacie, 3 rue du Professeur Laguesse, BP 83, F-59006 Lille Cedex. Tel : 03 20 96 40 08. benoit.foligne_AT_univ-lille.fr

 

description du projet : La bioremédiation in vivo consiste à limiter la biodisponibilité des éléments métalliques toxiques au niveau des muqueuses digestives pour en réduire l’accumulation dans l’organisme. Il est établi que des bactéries alimentaires ont une certaine affinité pour des métaux toxiques par des mécanismes passifs d’adsorption/séquestration, mais aussi par des processus actifs non élucidés, illustrant le concept «Probiotiques versus Xénobiotiques» [1]. Les bactéries du genre Lactobacillus ont montré une bonne aptitude à séquestrer les cations du plomb, du cadmium et des preuves d’efficacité vis-à-vis d’expositions aiguës ou chroniques ont été établies chez la souris, et plus récemment chez l’homme. Ces potentiels de détoxication sont très spécifiques selon les genres bactériens, mais aussi entre les souches au sein d’une même espèce. La biodiversité des bactéries commensales humaines offre aussi un large éventail de microorganismes à fort potentiel de bioremédiation, encore peu exploré. Le projet de Master 2 Recherche consistera à (i) identifier des microorganismes à forte capacité de captation vis-à-vis de quatre contaminants métalliques (Pb, Cd, As et Al) et (ii) en évaluer la performance protectrice dans des modèles précliniques, chez la souris.

[1]. Monachese et al. Bioremediation and tolerance of humans to heavy metals through microbial processes: a potential role for probiotics? Appl Environ Microbiol. 2012, 78(18):6397. 

Master 2 proposed in Team Dubuquoy (2)

Caractérisation fonctionnelle du pathovar Adherent-Invasif d’E.coli (AIEC).

Tuteur : Marie Titécat – LIRIC-U995 Inserm | Université de Lille  | CHU de Lille. Equipe Dubuquoy : Maladies Inflammatoires digestives : physiopathologie et développement de cibles thérapeutiques. Place Verdun 59045 Lille. Tel: 03 20 44 49 44. marie.titecat_AT_chru-lille.fr

 

description du projet : Le pathovar adhérent-invasif d’Escherichia coli (AIEC) est retrouvé avec une plus forte prévalence et une abondance accrue dans les muqueuses intestinales de patients atteints de maladies inflammatoires chroniques de l’intestin. A ce jour, aucun marqueur moléculaire fiable n’est disponible et l’identification des AIECs, essentiellement phénotypique, est relativement fastidieuse. Le sujet propose la mise au point d’un criblage automatisé à haut débit utilisant la microscopie de fluorescence. Cette méthode doit permettre l’identification, la quantification et la caractérisation de la virulence de clones d’E. coli à partir de prélèvements fécaux d’un patient. Elle repose sur l’analyse quantitative d’images représentatives de l’invasion de diverses lignées de cellules épithéliales et de macrophages par des bactéries marquées. Au-delà de l’intérêt évident en termes de diagnostic et de suivi de l’évolution de la maladie de Crohn, l’outil doit pouvoir servir à évaluer la contribution synergique ou antagoniste d’autres bactéries du microbiote intestinal, mais aussi à tester l’efficacité de molécules ciblées ou de probiotiques à visées anti-inflammatoires et anti-invasives. Les résultats ainsi obtenus in vitro seront corrélés in vivo dans le modèle Caenorhabditis elegans.

Thesis proposed by group FIRE in Team Vermersch/Mars (1)

Role of B cells in the Pathophysiology of Systemic Sclerosis (B-SCLERO)

thesis supervisor: David LAUNAY

mail: david.launay_AT_chru-lille.fr

 

details about the project :
Systemic sclerosis is a prototype of inflammatory diseases with extensive fibrosis. The immune system plays a major role in the pathophysiology of this disease. Among the different actors, B lymphocytes seem to play a central role as suggested by preliminary data et the presence of autoantibodies. The objectives of this project are 1. to describe the phenotypic and functional properties of circulating B lymphocytes/subpopulations in patients 2. to assess in an experimental model the phenotypic and functional properties of skin B cells. Innovative OMICs approaches (proteomic and transcriptomic) will allow assessing the impact of B cells on fibroblasts. This will allow studying anti B cell treatment in this disease and in a broader approach in fibrosing inflammatory disease.

keywords : systemic sclerosis, fibrosis, B lymphocytes, OMICs

required skills : Cell biology, culture, immunology, animal experimentation

-3im-53.pdf

Thesis proposed by Team Boulanger (1)

Role of diet in inflammaging: endogenous accumulation of glycation products and activation of specific receptors

Thesis supervisor: Frédéric TESSIER

mail : frederic.tessier_AT_univ-lille.fr

 

details about the project :
Carboxymethyl-lysine (CML) and other glycation products are found at high levels in several groups of commonly consumed processed foods such as coffee, chicory, ultra-processed cereal products, infant formula, etc. Exposure to CML in the perinatal period, and throughout life, raises health safety issues including its involvement in low-grade inflammation and aging.
The objective of this project is to understand by which biological mechanisms dietary CML accumulates in the body and promotes inflammation. Our team has already shown the toxicity of dietary CML on renal function and vascular health, but the originality of this study will be to reveal the biological mechanisms that cause the accumulation of CML in different tissues and organs.
Our strategy will be to use cell models and transgenic mice to discover the mechanisms by which dietary CML accumulates in some organs, but also how this glycation product can be eliminated after chronic exposure.
This thesis subject forms part of a larger, more ambitious program of understanding modifiable risk factors of aging (diet), and of developing anti-inflammaging therapeutic approaches.
This project aims to provide responses to mounting concerns surrounding the increasing consumption of ultra-processed foods potentially high in CML, and to be a decision aid for the agri-food industry to develop healthier foods

keywords: Glycation, inflammation, aging, nutrition, cell biology, animal models

required skills: cell biology, analytical biochemistry, animal experiment

-3im-95.pdf

Thesis proposed by Team Dubuquoy (3)

Study of the Role and Development of the Pathological Memory Immune Response in Inflammatory Bowel Diseases

thesis supervisor: Bertrand MERESSE

mail: bertrand.meresse_AT_inserm.fr

 

details about the project :
Background
Ulcerative colitis (UC) is a chronic inflammatory bowel disease that affects the epithelium of the colon. A variety of genetic and environmental factors have been implicated but the pathological mechanism is unknown. Our group have shown that the expression of the peroxisome-proliferator-activated receptor gamma (PPARg) is decreased in the gut epithelium of patients with UC. Yet, how the impaired expression of PPARg promotes epithelial lesions remains to determine.
Interestingly, PPARg regulates the expression of E-cadherin, a glycoprotein that has been associated with UC by genetic studies. E-cadherin is a ligand of the integrin CD103 expressed on intraepithelial lymphocytes (IELs); a population of resident memory T cells considered as the “sentinels” of the gut epithelium. Since CD103 is required to maintain and activate IELs within the epithelium we hypothesized that in UC their protective role could be impaired.

Study Aims
Thus, the aims of the study are:
1 - To assess the expression of E-cadherin on colonic intestinal epithelial cells in UC.
2 – To demonstrate that PPARg regulates E-cadherin expression in intestinal epithelial cells.
3 – To investigate consequences of the down regulation of PPAR and E-cadherin on the homeostasis and the activation of IELs.

Study Design
The proposal combines descriptive, analytic and experimental studies in both human and mouse models. The expression of E-cadherin and PPARg in the colonic epithelium and their consequences on CD103+ IELs will be studied in surgical specimens from patients with UC, crohn's disease or without inflammatory bowel diseases.
To demonstrate that PPARg influences retention and activation of iIELs through the regulation of the expression of the E-cadherin on intestinal epithelial cells, we will use Villin-crePPARgfl/fl or WT mice. These mice will also be infected with Citrobacter rodentium to evaluate the impact of PPARg on IELs during infection.

keywords : Crohn's disease, Ulcerative colitis, chronic inflammation, gut, memory cells

required skills : basic knowledge in immunology Skills: flow cytometry, cell culture, QRT-PCR

Thesis proposed by Team Gottrand (1)

GLP-2, a therapeutic factor to improve intestinal maturation for the preterm newborn?

thesis supervisor: Jean LESAGE

mail: jean.lesage_AT_univ-lille.fr

 

details about the project :
Premature births are in constant increase and represent 60 000 births / year in France. The rate of premature births in our region is the highest in France (9.4% versus 7.4% nationally). The prematurity of a child interrupts its development, and some of its organs are very immature. This mainly concerns the brain, lungs, ductus arteriosus and digestive tract. Gastrointestinal (GI) immaturity increases the risk of digestive intolerance, necrotizing enterocolitis (NEC) and septicemia in the short and medium term, exposing these newborns to an increased risk of mortality. To date, there is no pharmacological treatment that can improve the maturation and integrity of the intestinal barrier in preterm infants. GLP-2 is an intestinal hormone currently used clinically to stimulate the renewal of the intestinal mucosa and increase its absorption capacity in adults. This factor could represent a promising therapeutic in gastroenterology for the premature infant. The objectives of this project will be to evaluate: 1) the impact of GLP-2 on intestinal maturation; 2) the ability of GLP-2 to enhance the integrity of the intestinal barrier early. We will use an original murine embryo GI tract explant model to study the effects of GLP-2 on intestinal maturation. Explants from wild-type and transgenic mice, as well as a murine model of prematurity, will be used. Finally, a hypoxia-induced NEC model will test the effects of GLP-2 in pathophysiological conditions.

keywords: intestine, preterm babies, GI maturation, GLP-2, ex-vivo explants

required skills: animal experiments, explant culture, qRT-PCR, immunohistochemistry

Thesis proposed by Team Gottrand (2)

Effect of a hyper-protein diet on strengthening the intestinal barrier in acute graft-versus-host disease (aGvHD)

Thesis supervisor: David SEGUY

mail: david.seguy_AT_univ-lille.fr

 

details about the project :
Allogeneic hematopoietic stem cell transplantation (allo-SCT) following myeloablative conditioning (MAC) is the curative treatment for several haematological malignancies. In these patients, acute graft-versus-host disease (aGvHD), whose target organs are the intestine, liver and skin, is the leading cause of death.
The study of aGvHD in mice has revealed the impact of both intestinal epithelium damage and bacterial translocation following MAC on the apparition of aGvHD.
In humans, we have demonstrated that a low plasma citrulline level before MAC reflects the presence of subclinical intestinal damage which constitutes an independent aGvHD risk factor during the post-transplant period. Undernutrition and fasting increase the risk of aGvHD. In contrast, our team has shown that an early onset of enteral nutrition after allo-SCT decreases the incidence and severity of aGvHD in both adults and children. This is probably due to enteral nutrition's trophic action on the intestine.
In humans and mice, a protein deficient diet (or total parenteral nutrition) induces a decrease in small bowel mass that potentiates bacterial translocation while enteral amino acid supplementation reverses enterocyte atrophy.
We aim to demonstrate in mice that a high-protein diet limits the occurrence of aGvHD by strengthening intestinal barrier.

keywords: Chemotherapy/Radiotherapy - Intestinal barrier- Intestinal translocation - Graft-versus-host disease - Nutrition

required skills: Anomal experimentation - Histology - Immunochemistry - Microbiology - Flow cytometry - FITC dextran - qPCR - ELISA - Multiplex - SUNSET - PCNA - TUNEL

-3im-97.pdf

Thesis proposed by Team Gower (1)

Impacts of a food contaminant on the microbiota and intestinal homeostasis in humans

thesis supervisor: Cécile VIGNAL / Ariane LEROYER

mail: cecile.vignal2_AT_univ-lille.fr

 

details about the project :
Deoxynivalenol (DON), a mycotoxin produced by Fusarium species, is a frequent contaminant of grains and cereal products worldwide. DON causes many toxic effects on growth, immune response, reproduction, development… At the intestinal level, DON has been demonstrated to affect key immune functions which could lead to the induction and/or persistence of intestinal diseases. Study of the potential link between DON exposure and human Inflammatory Bowel Diseases (IBD) is the global aim of this proposal. Indeed, the different actors participating to the pathophysiological process leading to IBD development are still not well understood. We hypothesize that an improper detoxification of DON, implicating the gut microflora and/or endogenous enzymes, would lead to an increased susceptibility to DON toxicity in IBD patients. The objectives of this proposal are to compare, in healthy and IBD suffering individuals: 1) the cartography of DON absorption, distribution, metabolism and excretion; 2) the detoxification of DON by the gut and the consequences of DON exposure in term of immune homeostasis; 3) the effects of DON on the gut microbiota composition and the reciprocal effect of the gut microbiota on DON metabolism studied in vitro. The study of consequences of oral subchronic exposure of DON in humanized gnotobiotic mice colonized with a healthy or an IBD patient microbiota is our fourth objective. Our proposal is interdisciplinary bringing together gastroenterologists and researchers on nutrition, risk assessment, pathophysiology and microbiology.

keywords: dietary contaminant, gut microbiota, immunity, gut homeostasis

required skills: strictness, team work, motivation

Thesis proposed in Team Dubuquoy (1)

Factors Modulating Hepatocyte Regeneration in the Pathogenesis of Alcoholic Hepatitis, Cellular Mechanisms and Therapeutic Targets

 

thesis supervisor : Laurent DUBUQUOY / Sébastien DHARANCY

 e-mail : laurent.dubuquoy_AT_inserm.fr

details about the project :
Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease. Knowing that 40% of AH patients die very early from the consequences of liver damage, progresses in our understanding of the pathogenesis of the disease are mandatory. Researchers must identify the main mechanisms leading to death, in order to develop future therapies. Our previous original work suggests the need to explore the pathways of hepatocyte regeneration and hepatic progenitor differentiation. The objective of our research program is to better understand the cellular mechanisms responsible for the lack of regeneration that we have highlighted during AH in order to develop future targeted therapies, thanks to a multidisciplinary framework composed of clinicians and researchers. To achieve this goal we have access to unique liver samples from patients with AH. Approaches using cell isolation and culture, western blotting, immunohistochemistry and gene editing will identify and dissect the signaling pathways involved in the pathogenesis of HA.
This study should allow to radically change therapeutic strategies by identifying original targets and thus provide new solutions for the patient care. This project will benefit from the scientific, technical, material and infrastructural support necessary for its success.

keywords : alcoholic hepatitis, regeneration, hepatocyte, signaling pathways, pathophysiology

required skills : cell isolation and culture, molecular biology, ChIP