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Reference : UMR5239-MARDEL-002
Workplace : LYON 07
Date of publication : Monday, July 01, 2019
Scientific Responsible name : Marie DELATTRE
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 October 2019
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
The cell is a level of biological organization that has been poorly explored from an evolutionary perspective. How do cellular mechanisms evolve? What is the extent of possible solutions that have been retained over the course of evolution to achieve basic cellular functions? Our lab has established the nematode early embryo as a study system to address these questions.
Nematode embryos are ideal because they are large cells, their first cell division is very fast (15 minutes in C. elegans) and many subcellular events can be analyzed by simple DIC microscopy. Moreover, the one-cell embryo of the reference species C. elegans has been extensively studied both at the biophysical and molecular level, offering a framework to start comparative analysis.
We have developed two main axes: i) exploring which modification to female meiosis allows asexual reproduction (ex. ), ii) which molecular and physical changes are responsible for the different mechanics of the mitotic spindle between species (ex. ).
So far, functional explorations were difficult in non-model nematode species because both the RNAi technique and transgenesis were not accessible. Recent protocols have changed the situation  and we are now in a position to tackle our questions at the molecular level.
The goal of this PhD work will then be to i) establish the CRISPR/Cas9 technique in a couple of non-model nematode species displaying divergent phenotypes compared to C. elegans, ii) use this technology to start exploring the molecular basis of changes in meiotic and mitotic spindles over the course of evolution. For that, we will generate transgenic lines expressing fluorescent tags to perform time-lapse recording of live cells and create mutant lines for candidate genes. We will then be able to explore which modifications in cellular properties (microtubule and actin dynamics, cell cleavage, checkpoint activation, repartition of molecular motors, cytoplasmic viscosity, etc.) have led to the diversity of spindle mechanics between species.
. Grosmaire M, & al. Males as somatic investment in a parthenogenetic nematode. Science. 2019 Mar 15;363(6432):1210-1213. doi: 10.1126/science.aau0099.
. Valfort AC, & al. Evolution of mitotic spindle behavior during the first asymmetric embryonic division of nematodes.PLoS Biol. 2018 Jan 22;16(1):e2005099. doi: 10.1371/journal.pbio.2005099. eCollection 2018 Jan.
. Adams S, & al. Liposome-based transfection enhances RNAi and CRISPR-mediated mutagenesis in non-model nematode systems. Sci Rep. 2019 Jan 24;9(1):483. doi: 10.1038/s41598-018-37036-1.
LBMC is situated on the campus of the Ecole Normale Supérieure de Lyon (ENS-site Monod) in the south of the Lyon city center. ENS offers an interdisciplinary environment (30 research structures, from archaeology to quantum physics). The project is part of an intersdisciplinary and international research program (collaboration with IISER Pune, India).
Applicants must have a master or engineer degree in biology or biophysics. Background in either cell biophysics, cell biology, nematode biology, molecular genetics is required. Previous experience with the CRISPR/Cas9 system will be appreciated. We are looking for highly motivated candidates with a special interest for evolutionary questions or cellular biophysics. Good relational skills are important for the project, as it will be carried out in an interdisciplinary and international environment.
Please include a CV, a cover letter with the name of at least two references and a 1-page summary of your master thesis.
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