The CeDRE team « Reverse engineering cell division » (http:://pecreaux.openwetware.org) offers a PhD student position under the supervision of Jacques Pécréaux and Hélène Bouvrais at the Institute of Genetics and Development in Rennes (IGDR, CNRS UMR 6290/Univ. Rennes 1, dir. C. Prigent) Brittany, France. The Pécréaux group focuses on uncovering mechanisms of cell division through a multidisciplinary approach that combines cell biology, biophysics (modelling and in silico approaches), systems biology and image processing. The chosen candidate will contribute to understand the mechanisms of robustness for the positioning of the mitotic spindle and chromosome segregation using the nematode Caenorhabditis elegans as model organism. Funding will be granted upon success at the “Ecole doctorale” (Graduate school) competition, or will be obtained through applications to competitive fellowships. The candidate will receive support of the team in applying. The chosen candidate will also benefit of the PhD program of the institute (https://igdr.univ-rennes1.fr/en/training-jobs/training/our-phd-program).
Scientific environment:
The IGDR (http://igdr.univ-rennes1.fr/) is a vibrant research institute featuring established teams and dynamics new labs. Research covers genetics, regulation of expression, cell division, membrane trafficking and polarity. Furthermore, some teams are involved in translational research with CHU Rennes to study genetic diseases or some cancers, and a priority is to push forward interdisciplinary research.
Background:
The plasticity of cancer cells and the robustness of their divisions - despite antimitotic treatments and accumulated defects (e.g. chromosomal instability.) - appear as a major cause of cancer cells resistance to treatments. This robustness also makes the healthy cell, and its division, tolerant to defects whose accumulation will contribute to the oncogenic process. During cell division, sister chromatids are distributed to each daughter cell thanks to the mitotic spindle: improper chromosome segregation leads to aneuploidy, which is a common characteristic of cancer cells. Through which mechanisms does the mitotic spindle ensure its partition functions of chromosomes and its positioning as faithfully despite disturbances? To answer this question, we must explore the robustness of cell division with a paradigm shift to focus on mechanisms – involving networks of interacting players - instead of individual proteins. We will focus particularly on the major role of mechanical forces generated through the collective effects of different spindle elements, namely microtubules, molecular motors and their regulators.
Goals of the project:
How does the mitotic spindle divide the chromosomes in a robust and accurate way? To answer this difficult question, four operational steps are envisaged. (1) Develop robustness tests in control embryos to identify constrained points-candidates by studying the reproducibility of spindle motions between experiments. (2) Develop a functional approach of robustness points to determine which spindle functions, which mechanical forces, which spindle structures if necessary, we can associate to the robustness points identified in the undisturbed embryo. (3) Identify and functionally analyze physiological points of robustness: find the points which are solicited in case of defects tolerated by the cell, and identify the genes involved in this robustness. This will imply in particular the use of four tests of disturbance (change in cell size or in temperature, abnormal number of chromosomes, or the presence of chromosome attachment errors). (4) Recapitulate the mechanisms at the heart of cell division robustness of in a model combining analytical parties (based on physics equations), when possible, and a centered agent-based simulation for the parts where we know only the actors.
Requirements:
The candidate has a Master degree in biology or physics, with experiences in molecular cell biology or in soft matter physics. ● A strong interest for cell biology or biophysics and image processing, respectively, is mandatory, although no formal training or experience in these fields is required. ● The candidate is expected to be highly motivated, with excellent interpersonal and communication skills to collaborate in an interdisciplinary team. The candidate is able to communicate in English (spoken and written)
To apply (or for informal enquiries), please send (preferentially by email and PDF): A Curriculum Vitae (CV), a cover letter detailing your motivation and skills to take over the project, and the names of two referees.To Dr Jacques Pécréaux, jacques.pecreaux@univ-rennes1.fr, and Hélène Bouvrais, helene.bouvrais@univ-rennes1.fr, IGDR, CNRS UMR 6290 –Faculté de Médecine (Université Rennes 1), 2 avenue du Pr L. Bernard, CS34317, 35043 Rennes cedex, France
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