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Compartmentalization of the Drosophila gut: molecular organization and impacts on digestion and mucosal immunity

English title Compartmentalization of the Drosophila gut: molecular organization and impacts on digestion and mucosal immunity
Applicant Lemaitre Bruno
Number 146163
Funding scheme Project funding (Div. I-III)
Research institution Global Health Institute EPFL SV-DO
Institution of higher education EPF Lausanne - EPFL
Main discipline Genetics
Start/End 01.04.2013 - 31.03.2016
Approved amount 793'880.00
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Keywords (6)

gut; digestion; gene regulatory network; Drosophila; mucosal immunology; intestinal compartimentalization

Lay Summary (French)

Lead
Compartimentalisation de l'intestin chez la drosophile: organisation moléculaire et impacts sur la digestion et la réponse immunitaire
Lay summary

Le tube digestif est un organe central dans la biologie des animaux car il participe à la digestion et l’absorption des nutriments. Cet organe se caractérise par une succession de compartiments avec des propriétés génétiques, histologique et métaboliques différents. L’étude de cet organe a été négligée et les connaissances sur son organisation et ses différentes régions sont rudimentaires. Nous proposons d’étudier de manière extensive les mécanismes moléculaires participant à l’organisation de l’intestin en différentes régions chez la drosophile. Dans un premier temps, nous allons étudier quels sont les gènes impliqués dans la compartimentalisation de l’intestin.  Nous étudierons ensuite l’impact de cette régionalisation sur deux fonctions de l’intestin : la digestion et la réponse immunitaire. Les connaissances acquises permettront de mieux comprendre le fonctionnement du tube digestif chez les insectes, un classe d’animaux comprenant de nombreuses espèces impliquées dans la transmission de maladies à l’homme ou aux plantes. Considérant le fait que l’intestin est l’organe qui est apparut en premier au cours de l’évolution chez les métazoaires, il est probable que nos études révéleront des mécanismes moléculaires conservés, y compris dans des phyla distants comme celui les mammifères.

Direct link to Lay Summary Last update: 27.03.2013

Lay Summary (English)

Lead
Compartmentalization of the Drosophila gut: molecular organization and impacts on digestion and mucosal immunity
Lay summary

Although the gut is a central organ of animals, our understanding of its organization remains rudimentary. We propose an in-depth analysis of molecular mechanism required for the compartmentalization of the Drosophila adult intestine. In addition, we will monitor the impact of intestinal compartmentalization on the digestive process and intestinal immunity. Our findings will significantly improve our body of knowledge on the insect gut, which is the main route of transmission of several human parasites and the main target of insecticides. In evolutionary terms, gut compartmentalization is a conserved feature among animal phyla. Therefore, studies performed in Drosophila will also have a major impact on understanding regulatory programs crucial for proper gut function in mammals.

Direct link to Lay Summary Last update: 27.03.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Cell-Specific Imd-NF-κB Responses Enable Simultaneous Antibacterial Immunity and Intestinal Epithelial Cell Shedding upon Bacterial Infection
Zhai Zongzhao, Boquete Jean-Philippe, Lemaitre Bruno (2018), Cell-Specific Imd-NF-κB Responses Enable Simultaneous Antibacterial Immunity and Intestinal Epithelial Cell Shedding upon Bacterial Infection, in Immunity, 48(5), 897-910.e7.
Transforming Growth Factor β/Activin signaling in neurons increases susceptibility to starvation
Chng Wen-bin Alfred, Koch Rafael, Li Xiaoxue, Kondo Shu, Nagoshi Emi, Lemaitre Bruno (2017), Transforming Growth Factor β/Activin signaling in neurons increases susceptibility to starvation, in PLOS ONE, 12(10), e0187054-e0187054.
A genetic framework controlling the differentiation of intestinal stem cells during regeneration in Drosophila
Zhai Zongzhao, Boquete Jean-Philippe, Lemaitre Bruno (2017), A genetic framework controlling the differentiation of intestinal stem cells during regeneration in Drosophila, in PLOS Genetics, 13(6), e1006854-e1006854.
Physiological Adaptations to Sugar Intake: New Paradigms from Drosophila melanogaster
Chng Wen-bin Alfred, Hietakangas Ville, Lemaitre Bruno (2017), Physiological Adaptations to Sugar Intake: New Paradigms from Drosophila melanogaster, in Trends in Endocrinology & Metabolism, 28(2), 131-142.
Remote Control of Intestinal Stem Cell Activity by Haemocytes in Drosophila
Chakrabarti Sveta, Dudzic Jan Paul, Li Xiaoxue, Collas Esther Jeanne, Boquete Jean-Phillipe, Lemaitre Bruno (2016), Remote Control of Intestinal Stem Cell Activity by Haemocytes in Drosophila, in PLOS Genetics, 12(5), e1006089-e1006089.
Accumulation of differentiating intestinal stem cell progenies drives tumorigenesis.
Zhai Zongzhao, Kondo Shu, Ha Nati, Boquete Jean-Philippe, Brunner Michael, Ueda Ryu, Lemaitre Bruno (2015), Accumulation of differentiating intestinal stem cell progenies drives tumorigenesis., in Nature communications, 6, 10219-10219.
Genetic, molecular and physiological basis of variation in Drosophila gut immunocompetence.
Bou Sleiman Maroun S, Osman Dani, Massouras Andreas, Hoffmann Ary A, Lemaitre Bruno, Deplancke Bart (2015), Genetic, molecular and physiological basis of variation in Drosophila gut immunocompetence., in Nature communications, 6, 7829-7829.
Gut physiology mediates a trade-off between adaptation to malnutrition and susceptibility to food-borne pathogens.
Vijendravarma Roshan K, Narasimha Sunitha, Chakrabarti Sveta, Babin Aurelie, Kolly Sylvain, Lemaitre Bruno, Kawecki Tadeusz J (2015), Gut physiology mediates a trade-off between adaptation to malnutrition and susceptibility to food-borne pathogens., in Ecology letters, 18(10), 1078-86.
Microbiota-induced changes in drosophila melanogaster host gene expression and gut morphology.
Broderick Nichole A, Buchon Nicolas, Lemaitre Bruno (2014), Microbiota-induced changes in drosophila melanogaster host gene expression and gut morphology., in mBio, 5(3), 01117-14.
The Drosophila MAPK p38c regulates oxidative stress and lipid homeostasis in the intestine.
Chakrabarti Sveta, Poidevin Mickaël, Lemaitre Bruno (2014), The Drosophila MAPK p38c regulates oxidative stress and lipid homeostasis in the intestine., in PLoS genetics, 10(9), 1004659-1004659.
Transforming growth factor β/activin signaling functions as a sugar-sensing feedback loop to regulate digestive enzyme expression.
Chng Wen-bin Alfred, Bou Sleiman Maroun S, Schüpfer Fanny, Lemaitre Bruno (2014), Transforming growth factor β/activin signaling functions as a sugar-sensing feedback loop to regulate digestive enzyme expression., in Cell reports, 9(1), 336-48.
Functional analysis of PGRP-LA in Drosophila immunity.
Gendrin M, Zaidman-Rémy A, Broderick NA, Paredes J, Poidevin M, Roussel A, Lemaitre B (2013), Functional analysis of PGRP-LA in Drosophila immunity., in Plos one, 8(7), e69742.
Gut homeostasis in a microbial world: insights from Drosophila melanogaster.
Buchon N, Broderick NA, Lemaitre B (2013), Gut homeostasis in a microbial world: insights from Drosophila melanogaster., in Nature Review Genetics, 11(09), 615-624.
Morphological and molecular characterization of adult midgut compartmentalization in Drosophila.
Buchon N, Osman D, David FP, Fang HY, Boquete JP, Deplancke B, Lemaitre B (2013), Morphological and molecular characterization of adult midgut compartmentalization in Drosophila., in Cell Reports, 3(5), 1725-1738.
The digestive tract of Drosophila melanogaster.
Lemaitre B, Miguel-Aliaga I (2013), The digestive tract of Drosophila melanogaster., in Annual Review of Genetics, 47(-), 377-404.

Collaboration

Group / person Country
Types of collaboration
UNIL Lausanne Switzerland (Europe)
- Publication
Imperial College Great Britain and Northern Ireland (Europe)
- Publication
EPFL-Bart Desplancke Switzerland (Europe)
- Publication

Communication with the public

Communication Title Media Place Year
Media relations: radio, television Genes-et-intestin RTS Western Switzerland 2014

Associated projects

Number Title Start Funding scheme
166679 The Drosophila gut: molecular organization and impacts on physiology and immunity 01.04.2016 Project funding (Div. I-III)
165457 Function of the homeotic (Hox) genes in the compartmentalization of the adult Drosophila intestine 01.04.2016 International short research visits
166679 The Drosophila gut: molecular organization and impacts on physiology and immunity 01.04.2016 Project funding (Div. I-III)
141762 Quantitative and molecular genomics of Drosophila response to infection 01.11.2012 ProDoc
135703 The Drosophila intestinal epithelium: an immune barrier 01.04.2011 Project funding (Div. I-III)

Abstract

The importance of the gut in health and disease, as well as the mechanisms impacting on gut homeostasis, like the maintenance of intestinal stem cells, have only just begun to be unravelled. However, how this important organ is patterned in order to fulfil its diverse functions is largely unknown. We propose an in-depth analysis of regional regulatory networks required for compartmentalization of the Drosophila adult intestinal tract, a highly differentiated tissue maintained throughout an animal’s life. In addition, we will monitor the impact of intestinal compartmentalization on the digestive process and mucosal immunity. Investigating the regulation of digestive enzymes involved in carbohydrate degradation will also be part of this application. Studies addressing intestinal organization and physiology and, more generally, the question of how this organ functions as a whole are one of the most promising areas of research. Thus, one innovative aspect of our project is to apply approaches classically used in development to study function and physiology of a vital adult tissue. Our findings will significantly improve our body of knowledge on the insect gut, which is the main route of transmission of several human parasites and the main target of insecticides. In evolutionary terms, gut compartmentalization is a conserved feature among animal phyla. Therefore, studies performed in Drosophila will also have a major impact on understanding regulatory programs crucial for proper gut function in mammals.
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