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An integrated evolutionary and functional characterisation of the Drosophila immune peptidic secretome

Applicant Lemaitre Bruno
Number 186397
Funding scheme Sinergia
Research institution Institut suisse de recherche expérimentale sur le cancer EPFL SV ISREC
Institution of higher education EPF Lausanne - EPFL
Main discipline Interdisciplinary
Start/End 01.07.2019 - 30.06.2022
Approved amount 1'205'202.00
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All Disciplines (4)

Discipline
Interdisciplinary
Genetics
Immunology, Immunopathology
Information Technology

Keywords (9)

antimicrobial peptides; synteny-based orthology; comparative genomics; Innate immunity; Drosophila genetics; system genetics; Small ORF genes; phylogenomics; bioinformatic algorithms

Lay Summary (French)

Lead
Une approche intégrée en bioinformatique et génétique pour caractériser la réponse antimicrobienne peptidique de la drosophile.
Lay summary
Les insectes représentent environ 70% de l’ensemble des espèces animales et ont colonisé tous les écosystèmes terrestres. Comment font-ils pour se défendent contre les infections microbiennes ? Ont-ils développé des stratégies immunitaires particulières ? Voilà des questions au cœur de cette demande Sinergia. Les recherches sur les mécanismes immunitaires ont grandement bénéficié des travaux réalisés chez la drosophile, un modèle avec une large palette d’outils en génétique. Chez cet organisme, l'induction des peptides antimicrobiens au cours de la réponse immunitaire systémique a été bien caractérisée. Elle implique le corps gras et, dans une moindre mesure, les hémocytes (‘cellules sanguines’ de l’insecte), produisant une batterie d’effecteurs qui sont sécrétés dans l'hémolymphe (le ‘sang’ de l’insecte). En plus des peptides antimicrobiens, de nombreux autres peptides sont produits après infection. Ces effecteurs peptidiques sont mal caractérisés. En effet, les gènes de petite taille sont plus difficiles à définir et les outils traditionnels d’annotation des génomes ne sont pas suffisants pour les caractériser. Ce projet Sinergia réunit trois équipes ayant des compétences complémentaires en annotation des génomes (Robert Waterhouse), bioinformatique (Christophe Dessimoz) et génétique expérimentale (Bruno Lemaitre) dans le but de mieux caractériser la réponse antimicrobienne peptidique. L’objectif n’est pas seulement de mieux décrire la réponse immunitaire de la drosophile, mais aussi de développer des outils qui permettent l’étude des gènes codant pour des petits peptides. Ainsi, ce projet aura un impact bien au-delà des recherches sur l’immunité de l’insecte.
Direct link to Lay Summary Last update: 29.05.2019

Responsible applicant and co-applicants

Employees

Project partner

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Arthropod Genomics Symposium (virtual) Poster Evolutionary and functional characterisation of Drosophila immune peptides 21.07.2020 Lausanne, Switzerland Thiebaut Antonin;
SIB Days 2020 - virtual conference Poster Evolutionary and functional characterisation of Drosophila immune peptides 09.06.2020 Lausanne, Switzerland Thiebaut Antonin;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
SIB Days 2020 - virtual conference Workshop 08.06.2020 Lausanne, Switzerland Thiebaut Antonin;


Associated projects

Number Title Start Funding scheme
205085 Reconstructing ancestral microsyntenies across the tree of life, and inferring their impact on gene function and species adaptation 01.10.2021 Project funding (Div. I-III)
150654 Harnessing Phylogenetic Variation Among Genetic Loci to Unravel Species Phylogenies, Lateral Gene Transfer, and Recombination Hotspots 01.09.2015 SNSF Professorships
167149 Bio-SODA: Enabling Complex, Semantic Queries to Bioinformatics Databases through Intuitive Searching over Data 01.04.2017 NRP 75 Big Data
185295 The foreign within: Drosophila-Spiroplasma interaction as a model of insect endosymbiosis 01.05.2019 Project funding (Div. I-III)
167276 Efficient and accurate comparative genomics to make sense of high volume low quality data in biology 01.04.2017 NRP 75 Big Data
202669 Genomic innovations underlying arthropod success and diversity 01.09.2021 SNSF Professorships

Abstract

Life on Earth features complex interactions between diverse species, with both competition and cooperation but above all a critical requirement for effective self-defence mechanisms in the fierce struggle for survival. This has led to the invention and evolutionary refinement of intricate immune systems that determine the outcomes of health or infection. Understanding pathogen infection mechanisms and animal immune responses has revolutionised medicine and transformed human society. The study of invertebrate immune systems has played a crucial role in developing this understanding, with key findings in innate immunity such as the discovery of phagocytosis, antimicrobial peptides (AMPs) or the implication of Toll receptors in metazoan immunity. Elucidating immune mechanisms, genes, and signalling pathways has greatly benefited from studies in the fruitfly, Drosophila melanogaster, with a large suite of molecular genetics tools for manipulating the system. The induction of antimicrobial peptides (AMPs) as part of the systemic immune response is probably the best characterized immune reaction of Drosophila. The systemic immune response involves the fat body, and to a lesser extent haemocytes, producing immune effectors which are secreted into the haemolymph. It encompasses many more components than just AMPs, as illustrated by the Drosophila Bomanins that encode short peptides that mediate humoral immunity. Nevertheless, immune effectors that make up the immune peptidic secretome remain largely unknown and poorly characterised. This is mainly due to their short sizes and dynamic evolutionary histories that make them difficult to identify with traditional genome annotation and comparative genomics methods. Accumulating genomics data offer new possibilities to develop and apply computational approaches specifically designed to leverage evolutionary signals and target short peptides. At the same time, in-depth functional characterisation offered by CRISPR/Cas9 technologies means that new candidates emerging from computational surveys can be assayed for roles in antimicrobial or stress responses or yet-to-be-discovered humoral defence modules.Our project aims to develop the computational tools required to fully exploit new genomics data in a framework that also takes advantage of the latest molecular biology tools to achieve combined evolutionary and functional characterisation of the Drosophila immune peptidic secretome. We bring together expertise in insect immunity and functional assays from the EPFL team and computational and comparative evolutionary genomics expertise from the UNIL team. By focusing on immune effectors, our results will advance mechanistic insights into the dynamic interplay between pathogen growth and host immunity. This enhanced knowledge of Drosophila systemic responses will serve as a paradigm for innate immunity in general and have a wider impact on our understanding of animal host defence, thus, our project will offer novel insights into the forces that guide the evolution of the immune system.
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