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Maintenance of a dynamic steady state in the mitotic spindle studied by bottom-up biochemistry and micromanipulation of gene-edited cells


Intracellular Self-Organization

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Dr T Surrey No more applications being accepted Funded PhD Project (Students Worldwide)

About the Project

Background

The cytoskeleton is essential for the life of eukaryotic cells. Self-organized filament networks determine the function of the cytoskeleton. Correct coordination of protein activities is critical for the establishment of proper network states. One important task of the microtubule cytoskeleton is to build the mitotic spindle when cells divide to segregate the genetic material. A fascinating coordination task for the cell is to control spindle size, while at the same time microtubules depolymerize at spindle poles and polymerize in the spindle centre, as microtubules flux poleward. Several proteins, such as dynein and other molecular motors together with microtubule depolymerases are known to be involved in this process. However, the molecular mechanism that controls their coordinated action and leads to the establishment of a dynamic, yet stable steady state is not understood.

Project

We will use a synthetic bottom-up approach that allows to study cytoskeletal self-organization processes in minimal reconstituted systems. We will compare the behaviour of the reconstituted systems with that of custom-designed gene-edited cells. Methods to be used will be protein biochemistry, TIRF and confocal fluorescence microscopy, optical perturbations (laser cutting, photoactivation), gene-engineering in cultured human cells, etc. We will ask how the activities of plus and minus directed motors and microtubule dynamics regulators are coordinated to achieve the correct steady state organization. Our goal is to understand how the global characteristics of a biological system are produced by the self-regulated coordination of local molecular activities.

Environment

The Surrey lab recently relocated to the Centre for Genomic Regulation (CRG) in Barcelona, Spain. The overall goal of the lab is to understand how the cytoskeleton self-organizes and reorganizes itself, for example to form the mitotic spindle during cell division. The Surrey team has pioneered a number of fluorescence microscopy-based in vitro reconstitutions of dynamic microtubule cytoskeleton behaviour and contributed to advance our understanding of the molecular mechanisms underlying microtubule cytsokeleton function. The team is interdisciplinary consisting of biochemists, physicists and cell biologists. Advanced optical microscopy is a key method used in the lab. Recently CRISPR/Cas9 gene-editing in cultured human cells was established.

The PhD researcher will integrate at the CRG in Barcelona in a research center with international teams representing a broad range of disciplines, with first class core facilities to support the research project, a wide range of seminars given by high-profile invited speakers, and courses on complementary and transferable skills. He/she will be part of the PhD community at the CRG, which is highly active in organizing scientific and social activities.

Information on the Surrey lab:
https://www.crg.eu/en/programmes-groups/surrey-lab
Information on the CRG PhD Programme:
https://www.crg.eu/en/content/training/phd-students


Funding Notes

The selected PhD student will receive a work contract with a competitive salary that will be renewed annually for a maximum of 4 years following the applicable national regulations. The student will receive full health and occupational insurance coverage and will be included in the Spanish Social Security System.

Applications must be submitted online. Candidates must register in order to use the online application system:
https://recruitment.crg.eu/content/fellowships/calls/phd-call/crg-phd-call-2020

Application Deadline: 15 July 2020

References

Hannabuss J, Ramirez ML, Cade NI, Fourniol FJ, Nédélec F & Surrey T. Self-organization of minimal anaphase spindle midzone bundles. Curr Biol 29, 2120 - 2130 (2019)
Roostalu J, Rickman J, Thomas C, Nédélec F, Surrey T. Determinants of Polar versus Nematic Organization in Networks of Dynamic Microtubules and Mitotic Motors. Cell 175, 796-808 (2018).

Juniper M, Weiss M, Platzman I, Spatz SP, Surrey T. Spherical network contraction forms microtubule asters in confinement. Soft Matter 14, 901-909 (2018).

Dogterom M, Surrey T. Microtubule organization in vitro. Curr Opin Cell Biol 25, 23-9 (2013).
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