The ANR project "LoaGen", for Unveiling the population dynamics of the filarial worm Loa loa using population genetics, is led by a multidisciplinary team from two IRD research units: UMR 232 DIADE (Diversity, Adaptation, Development of Plants) and UMI233 TransVIHMI (Translational Research on HIV and Infectious Diseases). This project is carried out in collaboration with the Centre de Recherche sur les Filarioses et autre Maladies tropicales (CRFILMT), based in Yaoundé, Cameroon. The main part of the project will take place at the IRD research facility in Montpellier, but visits to our partner in Cameroon (1 to 2 per year) are to be considered.Scientific context
Loiasis is a parasitic disease caused by the worm Loa loa. It is transmitted by insect bites, an affects an estimated 20 million people living in the impoverished forest areas of Central Africa. In 2016, we showed that high grade L. loa infections were associated with reduced life expectancy. Yet, loiasis still lacks appropriate consideration by public authorities. We have undertaken a process to have loasis recognized as a public health problem by the World Health Organization, and thus to have it included in the list of Neglected Tropical Diseases.
In this study, we will apply a genetic epidemiology approach to document unknown aspects of the population dynamics of the parasite. Our approach will be, first, to generate complete and high quality L. loa genomes from samples collected in Cameroon. To do so, we will use the most advanced sequencing methods: whole genome by Illumina® and by Oxford Nanopore Technology®, then use the most performing bioinformatics tools for sequence assembly and analysis (e.g. Flye, Medaka, RagTag, Minimap2, Minigraph,...). We will develop a method for the individualization and sequencing of embryonic forms of L. loa, called microfilaria. This will allow us to exploit thousands of blood samples containing L. loa microfilariae available from our scientific partner in Cameroon, in the form of filter paper or on slides for microscopy.
We will then use polymorphic markers to address three practical issues:
1) Adult forms of the parasite live for more than 10 years in intermuscular fascia where they are impossible to detect. On the other hand, female worms produce microfilariae that invade the bloodstream where they are easily accessible. Based on the principle that microfilariae inherit part of the genetic heritage from their parents, we will estimate the number of reproductive parasites in a human host from the genetic diversity of microfilariae in that given host. Thus, we will analyze the within-host parasite genetic variability to deduce the effective population size.
2) The geographic range of loiasis is strictly African. It covers an area of about 3000 km from north to south, and 2000 km from east to west centered on the northern part of the Congo basin. The dispersal capacity of the vectors of loiasis, the chrysops, is a few kilometers. Using genetic markers, we will try to find out if the distribution area of L. loa is a wide homogeneous focus or, on the contrary, made up of separate transmission zones. We will therefore analyze the inter-host genetic variability of the parasite using samples taken in 5 geographical locations 60 km to 400 km apart and located in two distinct environmental zones of Cameroon (forest and savanna).
3) We have noticed, during therapeutic trials of ivermectin on L. loa, that while most microfilariae are eliminated within a few days, a significant proportion of microfilariae seem to survive the treatment. We hypothesize that the survival of these microfilaria is due to a particular genetic characteristic. We will collect samples of L. loa microfilariae from two groups of individuals participating in a therapeutic trial to evaluate the tolerance and efficacy of moxidectin vs. ivermectin on L. loa. The allelic compositions of the parasites present before and 7 days after treatment will be compared in each group to assess whether the parasites present after treatment have a particular genetic profile.
The biological and epidemiological parameters that we will document during this study will be particularly useful in defining optimal intervention strategies to eliminate loiasis.The research team
Under the responsibility of Sébastien Pion and François Sabot, researchers at IRD, your mission will be to ensure the production and bioinformatics analysis of sequencing data in order to answer scientific questions.
Your activities will be the following:
You have a PhD in ecology, evolution or epidemiology.Selection process
Start date : from 01 Novembre 2022, for a duration of 30 months
Send your application to email@example.com
Applications will be considered upon receiptAdditional comments
A French public research institution, IRD supports an original model of equitable scientific partnership and interdisciplinary, citizen, sustainability science committed to the achievement of the Sustainable Development Goals: L'IRD en 230 secondesRequired Research Experiences
1 - 4Offer Requirements
Vous avez développé les compétences suivantes :
Vous avez les qualités humaines suivantes :