Synthetic/chemical biology approaches to study multifunctionality of IDPs

1 PhD project proposal in the IPP summer call 2019

Scientific Background

In higher eukaryotes, proteins that lack apparent folded structure are enriched in many vital processes including formation of membraneless organelles. The Lemke group studies interactions with intrinsically disordered proteins in vital cellular processes, such as nuclear transport and gene regulatorion. Since such highly dynamic systems are inaccessible by most conventional approaches, the group applies a multidisciplinary approach combining synthetic biology, chemical biology, with super-resolution techniques.

PhD project proposal: Synthetic designer organelles and chemical biology tools to study multifunctionality of intrinsically disordered nucleoporins in the nucleus

As part of an ERC funded project “Next generation Single Molecule Protein Fluorescence” we are now looking for a PhD student  with a strong interest in synthetic biology, chemical biology and advanced genetic engineering of mammalian cells. We have now designed a synthetic, membraneless organelle in eukaryotes that is dedicated to perform protein engineering in cells. This basically allows the same cell to translate two different genetic codes. This is a scalable platform that enables to encode multiple new functionalities via new synthetics designer organelles into semi-synthetic organisms. We want to further develop this tool as a high end platform to engineer cells with fluorescent probes suitable for minimally invasive super-resolution microscopy.

The project is ideally suited for candidates with a strong background in chemical biology, synthetic biology, protein engineering, protein evolution, molecular biology and/or cell biology. Extensive on the project training will be provided so that candidates with little or even no prior no-hands on experience in the relevant experimental biosciences (such as synthetic chemists) but the strong wish to engage into those are also encouraged to apply. High interest and motivation are the main selection criteria. A strong interest in quantitative approaches in biology will help the person to blend in with the rest of the multidisciplinary team, which consist of biologists, chemists, biochemists, physicists and engineers.

Publications relevant to the project:

Reinkemeier CD, Estrada Girona G, Lemke EA (2019). Designer membraneless organelles enable codon reassignment of selected mRNAs in eukaryotes. Science. Mar 29;363(6434)

Nikić I, Estrada Girona G, Kang JH, Paci G, Mikhaleva S, Koehler C, Shymanska N V., Ventura Santos C, Spitz D and Lemke EA. (2016). Debugging eukaryotic genetic code expansion for site-specific click-PAINT super-resolution microscopy. Angew Chemie Int Ed, 55: 16172-16176.

Nikić I, Plass T, Schraidt O, Szymański J, Briggs JAG, Schultz C and Lemke EA. (2014). Minimal tags for rapid dual-color live-cell labeling and super-resolution microscopy. Angew Chemie Int Ed, 53: 2245-2249.

Koehler C, Sauter PF, Wawryszyn M, Estrada Girona G, Gupta K, Landry JJM, Hsi‐Yang Fritz M, Radic K, Hoffmann J-E, Chen ZA, Zou J, Tan PS, Galik B, Junttila S, Stolt‐Bergner P, Pruneri G, Gyenesei A, Schultz C, Biskup MB, Besir H, Benes V, Rappsilber J, Jechlinger M, Korbel JO, Berger I, Braese S, Lemke EA. 2016. Genetic code expansion for multiprotein complex engineering, Nature Methods. (12):997-1000

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