PhD in Modelling and Biostatistics

Updated: 5 months ago
Location: Gif sur Yvette, LE DE FRANCE
Deadline: 06 Nov 2019

The PhD candidate will be based in the “Evolution of Genomes, Behavior, and Ecology”, a mixed-research unit in Gif-sur-Yvette, France. He/She will be affiliated with the “Structure and Dynamics of Living Systems” doctoral school in Paris-Sud University. Research will take place in the “Evolution of Genomes” team, and will be supervised by Aurélie Hua-Van (Assistant professor, University Paris-Sud) and Arnaud Le Rouzic (CNRS Researcher).

The project is funded by the French National Research Agency (ANR TRANSPHORIZON, 2019-2022). The PhD candidate will thus be integrated into an active research group, and will benefit from this funding budget for expenses associated with the project. This ANR project will also fund the collection of experimental data on with this PhD project partly relies. The group has a solid knowledge in experimental evolution, bioinformatics, statistics, and theory in population genetics related to the evolution of transposable elements. The PhD candidate will be granted access to the computing resources (data storage and computing servers) that are necessary for the project.

* Scientific context

Transposable elements are repeated DNA sequences often constituting a substantial part of the genome content [1, 2]. Du to their ability to move and amplify, they are often considered as “selfish DNA” sequences, which evolutionary success does not depend on a selective advantage to the individuals carrying them [3, 4, 5].

Transposable elements are known to jump frequently across species borders and are able to invade new genomes after such horizontal transfer events [6]. Invasions are fast at the evolutionary scale, and difficult to study in nature. Yet, it is now possible to reproduce them in lab conditions, a procedure known as experimental evolution [7]. In our research lab, a research program devoted to the study of transposable element experimental invasions is being carried out in the model species Drosophila. Transposable element sequences from other species can be artificially introduced in the genome of lab flies, and such new element carriers can be introduces in experimental populations in which the element is not present. The number, frequency, and location of transposable element copies can then be followed through molecular biology techniques [8].

* PhD project

We are looking for a PhD student to focus on the analysis of these experimental data. The PhD project is defined along two axes, the first one corresponding to the definition of dynamic models, and the second one to bioinformatics analysis.

Dynamic, population genetics models will describe the evolution of the number and the frequency of transposable element copies in populations. They will be based on traditional models in transposable element population genetics [9, 10], although they will also consider recently-described mechanisms (such as the epigenetic-driven regulation of transposition through small RNA, [11]). Models will feature stochastic phenomena (genetic drift, recombination, mutations, sampling effetcs), and will be used for statistical inference of parameters of interest (such as transposition rates or regulation strength) from experimental data.

The bioinformatics analysis will deal with the data generated by sequencing the experimental populations. The PhD candidate will analyze the sequenced DNA fragments to infer transposable element insertion sites, as well as their frequencies in populations. Standard and/or ad-hoc statistical methods (such as site frequency spectrum analysis) will then be applied in order to reconstruct the evolution and the distribution of transposable elements during genome invasion.

* Required skills and training

We are looking for a student trained in bioinformatics, statistical methods, and dynamical model analysis. The PhD candidate should have basic training in computer sciences, including programming (programming languages used in our research group are R, Python, and C++). A solid experience in population genetics or evolutionary biology is also expected. Good level in written/spoken English is requested.

* References
[1] Wicker, T., Sabot, F., Hua-Van, A., Bennetzen, J. L., Capy, P., Chalhoub, B., ... & Paux, E. (2007). A unified classification system for eukaryotic transposable elements. Nature Reviews Genetics, 8(12), 973.
[2] Hua-Van, A., Le Rouzic, A., Boutin, T. S., Filée, J., & Capy, P. (2011). The struggle for life of the genome's selfish architects. Biology direct, 6(1), 19.
[3] Orgel, L. E., & Crick, F. H. (1980). Selfish DNA: the ultimate parasite. Nature, 284(5757), 604.
[4] Doolittle, W. F., & Sapienza, C. (1980). Selfish genes, the phenotype paradigm and genome evolution. Nature, 284(5757), 601.
[5] Le Rouzic, A., & Capy, P. (2005). The first steps of transposable elements invasion: parasitic strategy vs. genetic drift. Genetics, 169(2), 1033-1043.
[6] Gilbert, C., & Feschotte, C. (2018). Horizontal acquisition of transposable elements and viral sequences: patterns and consequences. Current opinion in genetics & development, 49, 15-24.
[7] Kawecki, T. J., Lenski, R. E., Ebert, D., Hollis, B., Olivieri, I., & Whitlock, M. C. (2012). Experimental evolution. Trends in ecology & evolution, 27(10), 547-560.
[8] Robillard, É., Le Rouzic, A., Zhang, Z., Capy, P., & Hua-Van, A. (2016). Experimental evolution reveals hyperparasitic interactions among transposable elements. Proceedings of the National Academy of Sciences, 113(51), 14763-14768.
[9] Charlesworth, B., & Charlesworth, D. (1983). The population dynamics of transposable elements. Genetics Research, 42(1), 1-27.
[10] Le Rouzic, A., & Deceliere, G. (2005). Models of the population genetics of transposable elements. Genetics Research, 85(3), 171-181.
[11] Czech, B., & Hannon, G. J. (2016). One loop to rule them all: the ping-pong cycle and piRNA-guided silencing. Trends in biochemical sciences, 41(4), 324-337.

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