PhD/Postdoc positions on Building a Synthetic Cell (BaSyC) (15.0 FTE)

Prof. Bert Poolman, Membrane Enzymology (b.poolman@rug.nl)
Prof. Dirk-Jan Slotboom, Structural Membrane Biology (d.j.slotboom@rug.nl)
We will design and synthesize vesicle systems for metabolic energy generation (ATP and electrochemical ion ...

25 dagen geleden

Arbeidsvoorwaarden

Standplaats:
Broerstraat, Groningen, Groningen
Dienstverband:
Tijdelijk contract / Tijdelijke opdracht
Opleidingsniveau:
WO

Functieomschrijving

Prof. Bert Poolman, Membrane Enzymology (b.poolman@rug.nl)
Prof. Dirk-Jan Slotboom, Structural Membrane Biology (d.j.slotboom@rug.nl)
We will design and synthesize vesicle systems for metabolic energy generation (ATP and electrochemical ion gradients) and equip them with mechanisms for cellular homeostasis (control of pH, ionic strength, redox). A further challenge will be to connect the energy conservation with ATP- and ion gradient-dependent reactions of the synthetic cells, including the uptake of sufficient nutrients and excretion of reaction products, and the synthesis of cell components. The vesicles will be equipped with fluorescence-based sensors to obtain quantitative data about the performance of the cells (fluxes, physiochemical conditions, volume). We have different projects for which expertise in protein chemistry, membrane biology, microfluidics and advanced microscopy (including data analysis) is required. PhD and Postdoc candidates will closely collaborate with colleagues in other teams to bridge the multidisciplinary challenges both in experimental work and theory.

Prof. Siewert-Jan Marrink, Molecular Dynamics (s.j.marrink@rug.nl)
One project centers around cell fission, a key step in cell replication. We will use classical molecular dynamics mostly based on the Martini coarse-grain model to be able to access the large spatio-temporal scales involved. Challenges are to predict how different lipid types and membrane proteins together with the cytoskeleton can help in generating the necessary curvature gradients and drive the final fission. The second project involves developing new multiscale simulation methods to bridge the gap between individual molecules to the scale of an entire cell. In particular, we would like to combine classical molecular dynamics simulations to chemical rate equations and to Green's function reaction dynamics. This combination of techniques allows us to extrapolate from the detailed molecular interactions all the way to the system's level, providing a solid theoretical framework for the synthetic cell project.

Prof. Matthias Heinemann, Molecular Systems Biology (m.heinemann@rug.nl)
From our recent work in yeast, we know that metabolic pathway activity is separated in time during the cell division cycle. We hypothesize that such temporal metabolic separation, for instance in protein and lipid synthesis, facilitates the cell division process. In this project, we will first study this in yeast (by means of microscopy, metabolic modeling, biophysical models) and then develop the respective ‘design models’ for the synthetic cell, and finally - in collaboration with the groups of Poolman and Driessen - will apply the gained insights to experimentally implement a metabolism-induced cell division. The programme outlined here includes major challenges, meaning that at least two PhD students/postdocs will work on this. The specific projects can be tailored to the prior experience and interest of the candidates, which could have a background from engineering, (bio)physics or molecular biology/biochemistry.

Prof. Arnold J.M. Driessen, Molecular Microbiology (a.j.m.driessen@rug.nl)
The project aims at the design and construction of a membrane system that grows from within vesicles by using a cascade of phospholipid biosynthesis enzymes and simple precursors that will be supplied from the outside. Further, the membrane biosynthesis module will be functionally integrated with other critical modules of synthetic cells. Specifically, this concerns the system for membrane protein biogenesis that is responsible for the functional integration of newly synthesized membrane proteins (transporters, membrane bound enzymes) into the lipid bilayers, as well as the system for metabolic energy generation to satisfy the energetic requirements for membrane biogenesis and protein synthesis. Ultimately, we aim to couple membrane growth to vesicle division. The project will be carried out in close collaboration with other teams of the BaSyC programme. Candidates with expertise in protein chemistry and membrane biology are preferred.

Prof. Giovanni Maglia, Chemical Biology (g.maglia@rug.nl)
One of the first events of cellular life was the formation of a permeable protective barrier that allowed the communication between the cell and the environment. The aim of this project is to recreate the spark that ignited cellular life by designing, engineering and evolving molecular components that specifically control cellular communication. This will recreate in vitro the evolutionary processes that lead to the formation of the complex control of transport of nutrients in living cells. One project consists of evolving small amyloid-forming peptides to partition into a lipid membrane to recreate an ancestral membrane protein. This process will shed light on the evolutionary origin of membrane proteins and the evolution of enzymatic functions. A second project will design artificial pore-forming proteins that, in analogy to outer membrane proteins, will allow the transport of molecules across membranes. Finally, we will develop a multicomponent molecular transporter that uses chemical fuel to actively transport molecules across a phospholipid membrane. These projects are ideally suited to scientists who have interest / experience in molecular biology, protein chemistry, protein engineering and (membrane) biophysics.

Functie-eisen

- the most important criteria are enthousiasm, excellence, commitment to research and team spirit; educational background preferably in the area of bioengineering, biochemistry, biophysics, multiscale modeling, systems biology or synthetic biology (see Job descriptions)
- candidates for a PhD position need to have completed a European master’s degree or equivalent prior to the application deadline; postdoc candidates need to have completed their PhD
- excellent proficiency in English language.

Conditions

Salary will be commensurate with experience (and type of position: PhD or Postdoc) and is in addition to a generous fringe benefit package.

Apply
To apply for one of the positions, please email a CV including a brief description of your research interests and accomplishments, and include two letters of recommendation from former advisors/professors. Correspondence to be addressed to Prof. Bert Poolman (BaSyC@rug.nl).

The deadline for application is 7 January 2018.

The starting date can be from February 2018 on until September 2019 and in exceptional cases also beyond.

Unsolicited marketing is not appreciated.

Additional information

The research groups: www.rug.nl/research/gbb/

Bedrijfsomschrijving

Faculty of Science and Engineering The University of Groningen provides an excellent environment for top-notch research in the field of biomolecular sciences. In the framework of a national programme on the construction of a synthetic cell, 15 PhD/Postdoc positions are available at the Groningen Biomolecular Sciences and Biotechnology Institute of the University of Groningen in the Netherlands.

The building of a synthetic cell is a great scientific and intellectual challenge for biophysicists, biochemists, and biologists. We aim to take on this challenge in the context of the NWO Gravitation Programme BaSyC (https://goo.gl/CMRpEZ). We will combine biomolecular building blocks to create an autonomous self-reproducing cell - a synthetic cell that can sustain itself, grow, replicate and divide.

15 PhD and Postdoc positions are available for both computational and experimental research: (i) to develop computational models at different levels of complexity with the aim to generate a feasible design of the synthetic cell; (ii) to experimentally reconstruct metabolism for cell fuelling, with the ability to produce energy carriers and molecular building blocks; (iii) to build pathways that are responsible for the biosynthesis of lipids and macromolecules and integrate these pathways into a synthetic cell, (iv) to design proteins de novo that control the molecular transport across protocell membranes.

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