PhD Position: Active Transcriptional Condensates in DNA Protonuclei (m/f/d)

The research group of Andreas Walther in collaboration with Jan Padeken offers the following PhD project:
Cells organize their most important chemistry in condensates - membrane-less compartments that concentrate enzymes, DNA and RNA. Transcription is a prime example: RNA polymerase II assembles into condensates whose architecture is set by its long, disordered C-terminal domain (CTD). How such condensates and transcription control each other is one of the open questions in the field, and it is hard to answer in living cells, where nothing can be varied independently.

So we build the answer instead using synthetic biology and DNA nanoscience. In the Walther lab we construct DNA synthetic cells and DNA protonuclei - programmable, DNA-based nucleus mimics whose crowded interior can be written with molecular barcodes, so that genes, polymerases and enzymes can be placed exactly where we want them. We have recently shown that transcription can be switched on and followed inside such protonuclei. Together with Jan Padeken (IMB Mainz) and Lukas Stelzl (JGU Mainz) within CRC/SFB 1551, we now want to rebuild active transcriptional condensates from the bottom up - with molecular simulations and C. elegans experiments as direct partners to the synthetic system.

PhD project: Transcription in DNA-Based Synthetic Cells

You will build DNA-based synthetic cells in which a gene can be switched on, watched and re-wired at will, and use them to ask how condensate organisation and transcription shape each other. Working with a chimeric T7::CTD polymerase, your tasks are roughly centred around:
- designing and building barcoded and multi-compartment DNA protonuclei that position genes, polymerases and enzymes with molecular precision
- running and quantifying transcription inside them, following RNA production and condensate dynamics by confocal microscopy and FRAP
- testing how the CTD, transcription factors and kinases/phosphatases tune transcriptional output - and how the nascent RNA feeds back on the condensates

This is a creative and highly interdisciplinary project at the interface of DNA nanoscience, synthetic biology and systems chemistry, with day-to-day exchange with the simulation (Stelzl) and in vivo (Padeken) groups. There is ample room to make the project your own.

We are looking for a highly motivated candidate with a very good degree in Molecular Biology, Synthetic Biology, Chemical Biology, Biochemistry or Chemistry, enthusiasm for interdisciplinary research and enjoyment of teamwork. Experience with nucleic acids, enzymes, protein purification or quantitative microscopy is a plus.

This project will be part of the CRC/SFB on Polymer Concepts in Cellular Function (crc1551.com), and is pending of this programme being supported by third party funding.

If you are interested in this project, please select Walther as your group preference in the IPP application platform.

Are you an ambitious scientist looking to push the boundaries of research while interacting with colleagues from multiple disciplines and cultures? Then joining the IPP is your opportunity to give your scientific career a flying start!
All you need is:

• Master or equivalent
• Interactive personality & good command of English
• 2 letters of reference