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Diego AYALA soutiendra son HDR le mercredi 3 février 2021 à 14h00 en visio*

 

Title

Natural and anthropogenic evolution of the malaria vector
Anopheles gambiae

 

Jury

Claudio Lazzari, Professeur Université Tours
Mathieu Joron, Directeur de Recherche CNRS, Rapporteur
Sarah Bonnet, Directrice de Recherche INRAE, Rapporteuse
Kenneth Vernick, Directeur de Recherche Institut Pasteur, Rapporteur,
Frederic Tripet, Professeur Université Keele

 

Abstract

I am interested in evolutionary processes driving adaptation and evolution in mosquito vectors. In particular, my research focuses on the ability of major malaria vectors to adapt to a broad range of environmental and ecological conditions. I combine different genomic, physiological and behavioral approaches towards a comprehensive understanding of natural populations of these mosquito vectors. My fieldworks activities span several Africa regions. I use my access to field in order to fill the gap between lab-based and field-based experiments. In the last time, I focus to understand the underlying mechanisms that lead Anopheles to adapt to anthropogenic habitats, and in consequence, to became vectors.

 

* membres du Mivegec, voir vos mails 'mivegec-tous' pour le lien

 

 

 

 

 

Monday the 21st of December 2020, at 2:00 PM, Benedicte FUSTEC will defend her PhD entitled

Exploring the potential of serological biomarkers to assess the risk of dengue transmission in north-Eastern Thailand

 

The defense will take place place by video conference*

 

The jury for the thesis will be composed of :
 ·      Jean Pierre Dedet (president of jury)
·      Lionel Almeras (referee)
·      Nicole L. Achee (referee)
·      Audrey Lenhart (examiner)
·      Richard Paul (examiner)
·      Vincent Corbel (director of thesis)
·      Hans J. Overgaard (co-supervisor of thesis)

 

Abstract :

In Thailand dengue epidemiology is seasonal and cyclical, yet outbreaks are particularly difficult to predict. Various epidemiological and entomological indices have been used for surveillance but they lack of reliability and accuracy for assessing dengue transmission risk. This thesis aims to develop more practical and sensitive tools and indicators of dengue transmission risk that may be used to forecast dengue outbreaks. A first retrospective epidemiological study showed that dengue incidence spatio-temporal pattern is strongly guided by climatic factors and urbanization. Serology surveys conducted through a randomized controlled trial evidenced a strong and positive “dose-response” association between Aedes adult abundance and the intensity of Ab response to Aedes salivary peptide, hence demonstrating the capacity of salivary biomarkers to assess fine-scale variations in Aedes-exposure risk. A case-control study conducted in the same area showed however that neither the level of Aedes infestation nor the intensity of Ab response to Aedes were good predictors of dengue and risk factors associated with dengue were age, house characteristics and the presence of DENV-infected Aedes at the patient house. This thesis highlighted the complex interactions between Aedes vectors, climatic and socioeconomic factors and dengue transmission risk in Thailand and discussed the implications for the development of more efficient warning indices to prevent outbreaks.

 

* MIVEGEC members: check your mails 'mivegec-tous' for the link to the videoconference

 

 

 

 Le mardi 15 décembre 2020 à 14h00, Manon VILLA défendrait sa thèse intitulée ;

Impact de l’utilisation des médicaments antipaludiques
sur
la transmission de Plasmodium sp.

 

en visioconférence devant le jury composé de :

M. Bruno FAIVRE, Pr. des Universités, Université de Bourgogne : Rapporteur
Mme Mathilde GENDRIN, Chargée de recherche, Institut Pasteur de Guyane : Rapporteur
M. Oliver KALTZ, Directeur de recherche, CNRS : Examinateur
Mme Alison DUNCAN, Chargée de recherche, CNRS : Examinateur
Mme Ana RIVERO, Directrice de recherche, CNRS : Directrice de thèse

 

Les membres du Mivegec peuvent trouver le lien pour le visioconférence parmi leurs mails de 'mivegec-tous'

 

Résumé de la thèse en français :

Le paludisme a encore aujourd’hui une incidence importante dans les populations humaines, notamment en Afrique sub-Saharienne, malgré le développement de médicaments antipaludiques. Ces derniers diminuent la mortalité et la morbidité liée à la maladie et peuvent impacter la transmission des parasites dans l’humain ou dans le vecteur. Les études sur les effets des médicaments antipaludiques sur la transmission du paludisme se sont pour le moment concentrées sur l’homme. Dans cette thèse, nous nous intéressons aux effets de deux antipaludiques majeurs, l’artésunate (AS) et la sulfadoxine-pyriméthamine (SP), sur la transmission du paludisme non seulement dans l’hôte vertébré mais aussi dans le vecteur. Grâce à un modèle de laboratoire, la malaria aviaire (Plasmodium relictum), nous avons montré que la SP diminue fortement la charge et la prévalence en sporozoïtes de moustiques infectés nourris sur des oiseaux traités et nous sommes en train d’étudier le lien avec le microbiome et le transcriptome dans le tube digestif du moustique. Ce médicament influence la transmission du paludisme en agissant directement sur les parasites dans le vecteur et de ce fait peut exercer une pression de sélection non seulement dans les humains traités (comme c'est largement accepté) mais aussi dans les vecteurs prenant un repas sanguin traité. Nous n’avons pas observé d’effet d’AS dans le vecteur. Par contre, lors d’une expérience au laboratoire utilisant des lignées de P. relictum sélectionnées pour être résistants à l'AS, nous avons observé que les coûts biologiques associés à la résistance à l’AS s’expriment dans le vecteur (diminution de l’intensité d’infection) mais pas dans le vertébré non traité. De plus, nous avons comparé la prévalence d’allèles de résistance sur les gènes pfcrt, dhfr et pfmdr de Plasmodium falciparum entre les hommes et les vecteurs dans 4 sites d’Afrique de l’Ouest. Nous avons mis en évidence une différence de prévalence d’allèles de résistance entre les hommes et les vecteurs, et même entre espèces vectrices. Ces différences peuvent représenter des coûts associés à la résistance ou mettre en lumière le rôle de sentinelle de la résistance des vecteurs pour des allèles de résistance en faible prévalence dans l’homme. Le vecteur est donc un maillon important dans l’étude de l’émergence et la propagation des allèles de résistance aux médicaments et de l’impact des antipaludiques sur la transmission du paludisme.

 

Résumé de la thèse en anglais :

Malaria incidence still is high especially in sub-Saharan Africa. Antimalarial drugs reduce the disease mortality and morbidity but could also impact the parasite's transmission. Current knowledge about the impact of drugs on malaria transmission come mainly from studies quantifying the transmissible blood stages of the parasite (gametocytes) in the vertebrate host. Our knowledge of how these drugs may impact the vector stages of the parasite is still very limited. In this thesis, I investigated the effects of two main antimalarial drugs, artesunate (AS) and sulfadoxine-pyrimethamine (SP), on parasite transmission through a series of laboratory experiments and field studies. Our laboratory experiments (with the avian malaria parasite, Plasmodium relictum) showed that SP decreases drastically sporozoite prevalence and burden and in infected vectors fed on SP-treated birds. We are currently studying the mechanistic underpinnings of these results by exploring the effect of the drug on the mosquito gut microbiome and transcriptome. Our results suggest that SP could exert a selection pressure not only in treated humans (as has been widely reported) but also in the vector feeding on treated humans. Our experiments didn’t show such an effect in mosquitoes fed on an AS-treated bloodmeal. In a separate experiment, where we selected for AS resistance in P. relictum, we were able to establish the existence of fitness costs linked to AS-resistance in the vector (lower intensity of infection) but not in the untreated vertebrate host. We have also compared the prevalence of 3 key drug resistance alleles (in the pfcrt, dhfr and pfmdr loci) between humans and vectors infected with the human malaria parasite Plasmodium falciparum across 4 different sites in West Africa. We show allele-dependent differences in prevalence both between humans and vectors, and between vector species. These differences may not only be indicative of the of costs of drug resistance being different for vectors and humans but also highlight the potential role of the vectors as sentinels for the detection of drug resistant mutations that are rare in humans. In sum, our results show the importance of investigating the effect of drugs on the vector stages of Plasmodium parasites for understanding the emergence and spread of drug resistance mutations on malaria transmission.

 

 

 

 

 

Monday the 14th of December 2020, at 2:00 PM, Jérôme BOURRET will defend his PhD thesis entitled

Measuring and understand codon usage bias:
collection of applications and evolution of paralogs and polyomaviruses

 

This PhD defence will be done by videoconference through StarLeaf. You can access it with the following link :

> https://meet.starleaf.com/4317852139/app

Apparently, the best solution is to download the StarLeaf app proposed by this like. This app won’t exactly install itself on your computer, but rather allow you to follow the defense.

 

Jérôme will defend this PhD thesis in front of a jury comprised of :

·      Céline Scornavacca (president)
·      Laurent Duret (referee)
·      Gwenael Piganeau (referee)
·      Anna-Sophie Fiston-Lavier (examiner)
·      Céline Bressollette (examiner)
·      Lucie Etienne (examiner)
·      Ignacio Gonzalez Bravo (PhD supervisor)
·      Samuel Alizon (PhD supervisor)

 

Abstract :

During the cellular translation process, the ribosomal machinery synthesizes a protein through the successive reading of codons along the messenger RNA. With each codon read, the ribosomes call upon the transfer RNAs, which are loaded with an amino acid (the basic unit of proteins). The complementarity between the codon on the mRNA and the anticodon on the tRNA is evaluated, eventually leading to the polymerization of the amino acid onto the nascent protein. There are 64 codons classically associated with 20 amino acids. Several codons, qualified as synonyms, can thus be associated with the same amino acid. Codon use bias (CUB) refers to the differential use of synonymous codons at the gene, genomic region or genome scale. CUB can be associated with mutational processes, at the origin of local peculiarities of nucleotide composition, but also with selection processes improving the protein synthesis dynamics. The influence of these two processes on CUB has been demonstrated in prokaryotes and in some eukaryotes. However, there is no strong evidence of selection acting at the Vertebrate gene level, and more specifically in mammals. Do we consider the CUB in these species from a correct angle? Do we have the necessary tools to draw such conclusions? To answer these questions, we propose a mathematical, computational and analytical approach to CUB through the analysis of vertebrate paralogs and human viruses.

We have designed a new CUB index called COUSIN (COdon Usage Similarity INdex), which quantifies the distance between the CUB of a sequence and that of a reference, and which stands out from other existing indices by its clarity in the interpretation of results. This index is implemented within an eponymous tool (http://cousin.ird.fr). In a second step, we performed a study of the evolutionary history and CUB of the Vertebrates paralogous genes Polypyrimidine Tract-Binding Protein (PTBP) whose tissue-specific expression could be associated with differences in their CUB. We show that PTBP1 paralogs appear to be mutagenically biased towards GC enrichment, while the CUB of PTBP2 paralogs may reflect a translational selection towards the use of rare codons in the genome. We interpret that the evolution of the CUB of PTBPs is compatible with a scenario of paralog sub-functionalization by differential expression during vertebrate development. Finally, we studied CUB in human viruses through human polyomaviruses (PyVs). Due to their obligate parasitism on the cellular protein synthesis machinery, the CUB of viruses could impact the clinical presentation of the infection. Our choice of human PyVs comes precisely from their genotypic diversity as well as their multiplicity of clinical manifestations. Infections with human PyVs are highly prevalent and asymptomatic but, in a context of immunosuppression, they can cause heavy and sometimes fatal tissue symptoms. Polyomavirus BK (BKPyV) is known to cause nephropathy in kidney transplant recipients. To prepare the analysis of longitudinal viremia, viruria and genetic data on kidney transplant patients, we have built two pipelines performing an analysis of the PyV genomes, and in particular of their genotype. In order to better understand the evolutionary dynamics of BKPyV in kidney disease, we have analyzed the evolution and CUB of PyVs in the context of the host-parasite relationship.

 

 

 

 

Akila YAGOUBAT va soutenir sa thèse que intitulée :

Unravelling the role of nucleoporins in the ploidy maintenance and genome integrity of trypanosomatids

 

- le vendredi 11/09/20 à 14h00 dans l'amphithéatre des Plantes à l'IRD.

 

Le jury est constitué par ;
Mélanie Bonhivers (CNRS, Univ. Bordeaux),
Lucy Glover (Institut Pasteur),
Luisa Miranda Figueiredo (Instituto de Medicina Molecular, Univ. of Lisbon),  
Kai Wengelnik (CNRS, Univ. Montpellier),
Artur Scherf (CNRS, Institut Pasteur), et
Patrick Bastien (Univ. Montpellier).

 

Du fait de la pandémie COVID, la soutenance sera réalisée par visioconférence; Mélanie Bonhivers sera la seule membre présente du jury.