Projects Offered

2 PhD projects offered in the IPP winter call Molecular Mechanisms in Genome Stability & Gene Regulation

Scientific Background

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 (CRC/SFB 1551), 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.

Publications relevant to this project

Xie M, Chen W, Vonk-de Roy M, Walther A (2025) Constructing synthetic nuclear architectures via transcriptional condensates in a DNA protonucleus.Nat. Commun. 16, 8254 Link

Fritzen J, Samanta A, Kuhr N, Preuss A, Sternburg E, Stelzl LS, Michels J, Dormann D, Walther A (2026) DNA protonuclei as programmable nuclear mimics reveal environmental context on protein phase separation. bioRxiv (accepted in Nat. Commun.) Link

Chen W, Dúzs B, Argudo PG, Bauer SV, Liu W, Samanta A, Parekh SH, Bonn M, Walther A (2025) Ballistic diffusion fronts in biomolecular condensates. Nat. Nanotechnol. 20, 1062 Link

Chen W, Song S, Samanta A, Sethi S, Drees C, Kappl M, Butt HJ, Walther A (2025) Growing functional artificial cytoskeletons in the viscoelastic confinement of DNA synthetic cells,Nat. Chem. Eng. 2, 627 Link

Chen W, Fritzen J, Walther A (2026) Phase separation of nucleic acids: mechanisms, properties, and applications, Angew. Chem. Int. Ed. 65, e202523943 Link

Samanta A, Baranda Pellejero L, Masukawa M, Walther A (2024) DNA-empowered synthetic cells as minimalistic life forms, Nat. Rev. Chem. 8, 454 Link

Samanta A, Hörner M, Liu W, Weber W, Walther A (2022) Signal-processing and adaptive prototissue formation in metabolic DNA protocells, Nat. Commun. 13, 3968 Link

Samanta A, Sabatino V, Ward TR, Walther A (2020) Functional and morphological adaptation in DNA protocells via signal processing prompted by artificial metalloenzymes, Nat. Nanotechnol. 15, 914 Link

Merindol R, Loescher S, Samanta A, Walther A (2018) Pathway-controlled formation of mesostructured all-DNA microgels and their superstructures, Nat. Nanotechnol. 13, 730 Link

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