Synthetic cell division mediated by membrane fission
Living cells have the remarkable ability to autonomously grow, divide and move. The Biological Soft Matter group at AMOLF uses bottom up synthetic biology to understand how the cytoskeleton and the plasma membrane of the cell work together to generate these complex biological functions. In this project, you will study the physical mechanisms needed for dividing cells to establish a force generating machinery that can physically divide the cell into two independent, equal compartments. This project is part of a large collaborative research programme called BaSyC (www.basyc.nl) aimed at creating a self-reproducing synthetic cell. The overarching goal is to use natural molecular building blocks and integrate them at increasing levels of complexity and autonomy to create a self-sustaining cell-like system. You will combine microfluidic and biochemical strategies to generate synthetic cells based on lipid vesicles, and use quantitative imaging and force spectroscopy to study how lipid- and protein-based mechanisms can together drive cell division. The goal is to engineer a combined minimal contractile ring and fission system that will pinch and split vesicles to two daughter vesicles.
More about the project
The BaSyC programme aims at combining biomolecular building blocks to create an autonomous self-reproducing cell. The project is a joint effort of 17 research groups from the TUD, AMOLF, Groningen University, Radboud University, Vrije Universiteit, and Wageningen University. The Koenderink group works on various aspects of the cytoskeletal machinery of the synthetic cell. This project will specifically focus on the final step of cell division: membrane splitting to yield two daughter cells. You will work closely together with other members of the group, who are developing the actomyosin machinery to drive membrane constriction and the regulatory modules to position the constriction machinery to the cell center. You will explore physical mechanisms that can be used to engineer a minimal machinery to accomplish synthetic cell division. You will first investigate lipid-assisted mechanisms of membrane fission and test whether these are able to complete division initiated by contractile ring constriction. Membrane fission normally involves a large energy barrier, but this barrier can be significantly lowered by lipid phase separation or insertion of topologically active lipids in one leaflet of the bilayer. You will investigate these lipid-assisted forms of division in vesicles, in collaboration with BaSyC partners at the TUD and Groningen University who develop synthetic lipid synthesis routes. You will next combine lipid-assisted mechanisms with protein-based strategies involving the ESCRT system.
The Biological Soft Matter group is an experimental research group centered around the soft condensed matter physics of living matter. Our central aim is to understand the physical mechanisms that govern the self-organization and (active) mechanics of cells and tissues. Our strategy is to reconstitute synthetic cell and tissue models from the bottom-up. We would ultimately like to take bottom-up reconstitution to the level where we can mimic complex cellular processes such as cell motility and tissue development. Synthetic systems allow us to identify the physical principles that underlie the complex functions of living matter and facilitate close coupling between experiments and predictive modelling. We study synthetic cells and tissues using quantitative microscopy combined with mechanical tools such as optical tweezers and rheometry. We actively collaborate with theoretical groups and with cell and developmental biologists.
You need to meet the requirements for a doctors-degree and must have research experience in a non-Dutch academic environment. We expect you to have experience in soft matter and/or cell biophysics. We are looking for an outstanding and motivated person with experience with protein and/or lipid biochemistry and with quantitative biophysical techniques such as advanced microscopy, microfluidics, or force spectroscopy. We furthermore look for people who are enthusiastic about the idea of working in a collaborative, ambitious and international environment. The BaSyC programme is characterized by strong collaboration among the groups, located at the different institutes. You should therefore be enthusiastic about working at different locations and collaborating with researchers from other disciplines. Good communication skills in oral and written English is a must.
You will be offered an employment of 2,5 years in the service of NWO-I with excellent employment benefits. The position is intended as full-time (40
AMOLF is a small-scale institute with different disciplines and is known for its unique collaborative culture. Your development will be stimulated in the form of training on the job together with relevant courses. We offer generous relocation expenses and support with finding housing and visa application. NWO-I also offers you facilities to combine work and private life, like partly paid parental leave. Curious about our other benefits? See the employment regulations of NWO-I.
You will join a vibrant research institute that provides access to world-class infrastructure and a worldwide network of collaborators spanning across disciplines. You will furthermore have access to all research facilities and training events in the framework of the BaSyC programme, including a training program at the different partners’ institutions for instructions in protein/gene handling, advanced optical microscopy, and computational methods, as well as training on the ethical and societal aspects of synthetic biology.
Prof.dr. Gijsje Koenderink
Group leader Biological Soft Matter
Phone: +31 (0)20-754 7100
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