Differences in mutational processes and intratumour heterogeneity between organs: the local selective filter hypothesis.

International audienceExtensive diversity (genetic, cytogenetic, epigenetic and phenotypic) exists within and between tumors, but reasons behind these variations, as well as their consistent hierarchical pattern between organs, are poorly understood at the moment. We argue that these phenomena are, at least partially, explanable by the evolutionary ecology of organs’ theory, in the same way that environmental adversity shapes mutation rates and level of polymophism in organisms. Organs in organisms can be considered as specialized ecosystems that are, for ecological and evolutionary reasons, more or less efficient at supressing tumours. When a malignancy does arise in an organ applying strong selection pressure on tumours, its constituent cells are expected to display a large range of possible surviving strategies, from hyper mutator phenotypes relying on bet-hedging to persist (high mutation rates and high diversity), to few poorly variable variants that become invisible to natural defences. In contrast, when tumour suppression is weaker, selective pressure favouring extreme surviving strategies is relaxed, and tumours are moderately variable as a result. We provide a comprehensive overview of this hypothesis

Characteristics of meiofauna in extreme marine ecosystems: a review

Extreme marine environments cover more than 50% of the Earth’s surface and offer many opportunities for investigating the biological responses and adaptations of organisms to stressful life conditions. Extreme marine environments are sometimes associated with ephemeral and unstable ecosystems, but can host abundant, often endemic and well-adapted meiofaunal species. In this review, we present an integrated view of the biodiversity, ecology and physiological responses of marine meiofauna inhabiting several extreme marine environments (mangroves, submarine caves, Polar ecosystems, hypersaline areas, hypoxic/anoxic environments, hydrothermal vents, cold seeps, carcasses/sunken woods, deep-sea canyons, deep hypersaline anoxic basins [DHABs] and hadal zones). Foraminiferans, nematodes and copepods are abundant in almost all of these habitats and are dominant in deep-sea ecosystems. The presence and dominance of some other taxa that are normally less common may be typical of certain extreme conditions. Kinorhynchs are particularly well adapted to cold seeps and other environments that experience drastic changes in salinity, rotifers are well represented in polar ecosystems and loriciferans seem to be the only metazoan able to survive multiple stressors in DHABs. As well as natural processes, human activities may generate stressful conditions, including deoxygenation, acidification and rises in temperature. The behaviour and physiology of different meiofaunal taxa, such as some foraminiferans, nematode and copepod species, can provide vital information on how organisms may respond to these challenges and can provide a warning signal of anthropogenic impacts. From an evolutionary perspective, the discovery of new meiofauna taxa from extreme environments very often sheds light on phylogenetic relationships, while understanding how meiofaunal organisms are able to survive or even flourish in these conditions can explain evolutionary pathways. Finally, there are multiple potential economic benefits to be gained from ecological, biological, physiological and evolutionary studies of meiofauna in extreme environments. Despite all the advantages offered by meiofauna studies from extreme environments, there is still an urgent need to foster meiofauna research in terms of composition, ecology, biology and physiology focusing on extreme environments

Multiple Changes in Peptide and Lipid Expression Associated with Regeneration in the Nervous System of the Medicinal Leech

peer reviewe

Caractérisation et étude fonctionnelle des acteurs de la réponse immunitaire du système nerveux de la sangsue (Hirudo medicinalis)

A la différence des mammifères le système nerveux central (SNC) de la sangsue médicinale, possède la faculté de régénérer ses neurites et ses connexions synaptiques suite à une lésion. Notre équipe a démontré que ce processus de régénération était favorisé par une infection bactérienne contrôlée. Le premier axe de ma thèse fut d étudier le lien entre, l'activation de la réponse neuroimmunitaire et le processus de régénération, par l étude de trois effecteurs récemment caractérisés au sein de la chaîne nerveuse de sangsue: deux peptides antimicrobiens (PAMs) (l Hm-lumbricine et la neuromacine) et une cytokine-like, nommée Hm-EMAP II. Les résultats obtenus démontrent pour la première fois (i) une synthèse neuronale de PAMs possedant une activité neurotrophique en plus de leur activité antimicrobienne et (ii) l effet chimiottractant d EMAP II vis-à-vis des cellules microgliales humaines et de sangsue, donnant pour la première fois une fonction à cette cytokine dans le SNC humain. En effet, même si EMAP II est décrit comme un marqueur de réactivité des cellules microgliales du cerveau humain lésé, sa fonction dans cet organe n'a pas encore été élucidée. Le contact étroit entre le sang et la chaîne nerveuse nous a conduits dans un second temps, à explorer la participation de ce liquide biologique dans la réparation neuronale de notre modèle. Nos données montrent, qu en plus d'exercer des fonctions immunitaires périphériques, le sang de sangsue optimise la réparation du SNC, par la libération de substances neurotrophiques. Les cellules sanguines s avèrent également capables d infiltrer le site de lésion où, en coopération avec les cellules microgliales, elles limitent la formation d'un manchon cicatriciel. Chez les mammifères, les blessures du SNC conduisent à la mise en place d'une cicatrice gliale, qui bloque le mécanisme de régénération en empêchant la repousse axonale du SNC. Les résultats présentés ici constituent la première description d une fonction neuro-immunitaire des cellules sanguines chez un invertébré. L'ensemble de ces données présentent le SNC de sangsue comme un modèle intéressant pour étudier le lien entre immunité et réparation neuronale.Following trauma, the central nervous system (CNS) of the medicinal leech, unlike the mammalian CNS, has a strong capacity to regenerate neurites and synaptic connections that restore normal function. Our team demonstrated that this regenerative process is enhanced by a controlled bacterial infection. As a first step of my PhD, the interaction between the activation of a neuroimmune response and the process of regeneration were explored by studying the role of three effectors newly characterized from the leech nerve cord: two antimicrobial peptides (AMPs) (Hm lumbricin and neuromacin) and one cytokine-like named Hm-EMAPII. Altogether the obtained results allowed reporting for the first time (i) the neuronal synthesis associated with a neurotrophic effect of AMPs and (ii) the ability of EMAPII to exert chemoattractant effect towards both leech and human microglial cells giving a function to this cytokine in the human SNC. Indeed, even if EMAPII is described as a marker of microglial cell reactivity in injured human brain, its function in the neural immunity has not been yet elucidated. As a second step of my PhD, the close contact of the blood with the nerve cord conducted us to explore the participation of blood in neural repair in our model. Our data evidenced that in addition of exerting peripheral immune functions, leech blood optimizes CNS neural repair through the release of neurotrophic substances. Circulating blood cells appeared also able to infiltrate the injured CNS where, in conjunction with microglia, they limit the formation of a scar. In mammals, CNS injury conducts to the generation of a glial scar that blocks the mechanism of regeneration by preventing axonal regrowth. The results presented here constitute the first description of neuroimmune functions of invertebrate blood cells. Altogether these studies introduce the leech CNS as an interesting model for studying the implication of immune molecules in neural repair.LILLE1-Bib. Electronique (590099901) / SudocSudocFranceF

Neuro-immune lessons from an annelid: The medicinal leech

International audienc

Caractérisation et rôle des peptides antimicrobiens dans l'immunité innée de la sangsue Theromyzon tessulatum

LILLE1-BU (590092102) / SudocSudocFranceF

Antagonistic evolution of an antibiotic and its molecular chaperone: how to maintain a vital ectosymbiosis in a highly fluctuating habitat

International audienceEvolution of antimicrobial peptides (AMPs) has been shown to be driven by recurrent duplications and balancing/positive selection in response to new or altered bacterial pathogens. We use Alvinella pompejana, the most eurythermal animal known on Earth, to decipher the selection patterns acting on AMP in an ecological rather than controlled infection approach. The preproalvinellacin multigenic family presents the uniqueness to encode a molecular chaperone (BRICHOS) together with an AMP (alvinellacin) that controls the vital ectosymbiosis of Alvinella. In stark contrast to what is observed in the context of the Red queen paradigm, we demonstrate that exhibiting a vital and highly conserved ecto-symbiosis in the face of thermal fluctuations has led to a peculiar selective trend promoting the adaptive diversification of the molecular chaperone of the AMP, but not of the AMP itself. Because BRICHOS stabilizes beta-stranded peptides, this polymorphism likely represents an eurythermal adaptation to stabilize the structure of alvinellacin, thus hinting at its efficiency to select and control the epibiosis across the range of temperatures experienced by the worm; Our results fill some knowledge gaps concerning the function of BRICHOS in invertebrates and offer perspectives for studying immune genes in an evolutionary ecological framework

Polychaetes as annelid models to study ecoimmunology of marine organisms

International audienc