Workpackage : WP1
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Our team is highly interdisciplinary. It brings together students and researchers from a variety of disciplines, including pharmaceutical sciences, medical sciences, biochemistry, molecular biology and physiology, to work side by side. Current members of the team are: Jean-Luc Desseyn, PhD, HDR, head Valérie Gouyer, PhD, HDR, Eng. CHU Ségolène Plet, Tech. Mylène Magnien, Tech. Frédéric Gottrand, MD, PhD, PUPH David Séguy, MD, PhD, PUPH (adjunct to the group) Guillaume Lacroix, Thesis D2 Previous PhD students: Hélène Valque, PhD (2008-2011), Project leader/Eng., Servier Labs, France Céline Portal, PhD (2013-2016), Postdoctoral fellow, Johns Hopkins University, Wilmer Eye Institute, Baltimore Bastien Demouveau, PhD (2016-2019), Project manager at OptimHal-pProtecSom, France Salah Amini, Postdoc (under supervision of D. Séguy) |
[Recent achievements] [Events] [Publications][Gallery]
Research topics
The laboratory uses recombinant molecules, cellular biology, genetically modified murine models and in vivo imaging as part of an integrated approach (i) to study the mechanistic basis of human diseases linked to mucus and mucins, (ii) to identify new biomarkers and (iii) to develop innovative therapeutic treatments. We examine the mechanisms involved in the protection by the mucus hydrogel of the underlying epithelium (nose, trachea, lung, intestine, ear, eye, vagina) and how we can modulate the mucus properties. | ![]() |
Recent achievements |
Our events |
2019 |
June 2020: The next Gordon Research Conference on Cilia, Mucus and Mucociliary Interactions has been postponed to the week of May 2-7 and relocated to Switzerland (Les Diablerets).
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[Top][Recent achievements] [Events] [Gallery]
Publications
Articles |
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Impact and consequences of intensive chemotherapy on intestinal barrier and microbiota in acute myeloid leukemia: The role of mucosal strengthening |
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Importance of the Phospholipid Core for Mucin Hydrogel Penetration and Mucosal Cell Uptake of Maltodextrin Nanoparticles |
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Mucin CYS domain stiffens the mucus gel hindering bacteria and spermatozoa |
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Early life nutrition influences susceptibility to chronic inflammatory colitis in later life |
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Muc5b-deficient mice develop early histological lung abnormalities |
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Muc5b is mainly expressed and sialylated in the nasal olfactory epithelium whereas Muc5ac is exclusively expressed and fucosylated in the nasal respiratory epithelium |
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Non-C-mannosylable mucin CYS domains hindered proper folding and secretion of mucin |
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Long-term dietary (n-3) polyunsaturated fatty acids show benefits to the lungs of Cftr F508del mice |
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Systematic gene overexpression in Candida albicans identifies a regulator of early adaptation to the mammalian gut |
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In vivo imaging of the Muc5b gel-forming mucin |
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Preclinical mouse model to monitor live Muc5b-producing conjunctival goblet cell density under pharmacological treatments |
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Delivery of a mucin domain enriched in cysteine residues strengthens the intestinal mucous barrier |
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Dietary pectin-derived acidic oligosaccharides improve the pulmonary bacterial clearance of Pseudomonas aeruginosa lung infection in mice by modulating intestinal microbiota and immunity |
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Impact of fish oils on the outcomes of a mouse model of acute Pseudomonas aeruginosa pulmonary infection |
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Pectin-Derived Acidic Oligosaccharides Improve the Outcome of Pseudomonas aeruginosa Lung Infection in C57BL/6 Mice |
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Assembly of the respiratory mucin MUC5B: a new model for a gel-forming mucin |
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MUC5B leads to aggressive behavior of breast cancer MCF7 cells |
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The mucin MUC4 and its membrane partner ErbB2 regulate biological properties of human CAPAN-2 pancreatic cancer cells via different signalling pathways |
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Abnormal expression of Muc5b in Cftr-null mice and in mammary tumors of MMTV-ras mice |
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(n-3) long-chain PUFA differentially affect resistance to Pseudomonas aeruginosa infection of male and female cftr–/– mice |
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The extraordinarily complex but highly structured organization of intestinal mucus-gel unveiled in multicolor images |
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The characterization of the first anti-mouse Muc6 antibody shows an increased expression of the mucin in pancreatic tissue of Cftr-knockout mice |
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Dietary (n-3) polyunsaturated fatty acids affect the kinetics of pro- and antiinflammatory responses in mice with Pseudomonas aeruginosa lung infection |
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Mucin CYS domains are ancient and highly conserved modules that evolved in concert |
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Autocrine induction of invasion and metastasis by tumor-associated trypsin inhibitor in human colon cancer cells |
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Dietary n-3 fatty acids have suppressive effects on mucin upregulation in mice infected with Pseudomonas aeruginosa |
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Epigenetic regulation (DNA methylation, histone modifications) of the 11p15 mucin genes (MUC2, MUC5AC, MUC5B, MUC6) in epithelial cancer cells |
Reviews |
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The cervicovaginal mucus barrier |
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Ocular mucins in dry eye disease |
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Transgenic mouse reporter to study Muc5b in vivo |
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Gel-forming mucin interactome drives mucus viscoelasticity |
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Early-life origin of intestinal inflammatory disorders |
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Biological modeling of mucus to modulate mucus barriers |
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Modulation of host defence against bacterial and viral infections by omega-3 polyunsaturated fatty acids |
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Long chain polyunsaturated fatty acids: immunomodulators in disease |
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Architecture of the large membrane-bound mucins |
General audience |
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La structure des mucines conditionne les propriétés viscoélastiques des gels de mucus |
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Différenciation des cellules à mucus et régulation de la mucine gélifiante Muc5b : un nouvel outil pour des études ex vivo et précliniques in vivo |
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Le défaut de mucus intestinal, nouvelle cible thérapeutique |
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Modification à façon des propriétés physiques du mucus. Preuve de concept et applications potentielles |
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Maladie de l'intestin - Renforcer le mucus pour mieux protéger |
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Organisation du gène de mucine humaine MUC5B et bases moléculaires d’une nouvelle classification des gènes de mucines |
Biological tools |
Antibodies
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Anti mouse-Muc6 antibody (rabbit polyclonal). Directed against the peptide TSKIPVTQTTTHRVPSRCIT, which is N-terminal to the tandem repeats of Muc6 (amino acids 1,387–1,406, GenBank: AY184388.1). For WB and IHC, available upon request. ← serial sections showing strong labelling of the deep gland cells with the anti-Muc6 antibody (CP4), and Muc6 within the gel layers, while Muc5ac was synthesized in the superficial/foveolar epithelium in agreement with the human distribution. |
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Anti mouse-Muc5b antibody (rabbit polyclonal). Directed against the 19 aa peptide DVSSGLVCYNKDQGGTFQM found in CYS domains #2/3/5 of Muc5b. For IHC, available upon request. |
Construct
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Mini5B expression plasmid: Eucaryotic hybrid promoter + intron + Mini5B + Ires-Luc. The plasmid contains a Neo cassette for stable transfection. The mini5B is made of two MUC5B CYS domains flanking a full TR array of MUC5B with a functional N-glycosylation site at the C-term. |
Transgenic mouse lines
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Tff3-rCYSx12-eGFP. Mouse Tg(Tff3/MUC5B-meGFP)1Jlcd: Tff3 promoter driving the production/secretion of a meGFP-tagged CYSx12 (human MUC5B) recombinant molecule with Muc2 in the mouse intestine. With its large Tff3 (mItf) promoter, this transgenic mouse can be used as a Tff3 eGFP-reporter mouse. Available under a collaborative MTA.
Tff3-rCYSx12. The variant without the eGFP tag (named Tg208 or K208/Tg(Tff3/MUC5B)1Jlcd) has been deposited and is available at EMMA. Homozygotes are viable. For details, see MGI/Jax. |
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Muc5b-meGFP/Muc5b knockout Mouse eGFP reporter for Muc5b obtained by homologous recombination (knockin). The full Muc5b glycoprotein is labelled with a monomeric eGFP tag. The last two exons of Muc5b are floxed, giving the opportunity to generate any conditional Muc5b knockout. Available under a collaborative MTA. |
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Muc4 knockout. Mouse Muc4 knockout was obtained by gene targetting. The first exon was removed. This transgenic model has not been published. Available under a collaborative MTA. |
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