Project (Patrick Cramer)

We are uncovering the molecular mechanisms and systemic principles of genome transcription and regulation. Over the next year we will recruit highly motivated and talented PhD students from various disciplines. Our laboratory can offer PhD projects in (A) functional genomics, (B) computational biology, and (C) Biomolecular condensation by liquid-liquid phase separation. Below please find possible projects, which will be further developed together with candidates interested in certain areas.

A, B: We have recently developed the experimental and computational tools for TT-seq, a method that enables measuring of RNA synthesis rates (1) and mapping of enhancer landscapes in a dynamic way in vivo (1, 2). Based on these successes we will use TT-seq to follow cell differentiation events and cellular responses to hormones and other signals. Combining these data with further genome-wide data sets from ChIP-seq, ATAC-seq or mNET-seq will enable us to study the principles of changing gene expression programs. Work on these projects requires talented experimentalists (with a background in the life sciences) and computational biologists (with a background in mathematics, informatics etc. and a strong interested in biology and biomedicine). The aim of these projects is to uncover the mechanisms of gene regulation in living cells.

C: We have recently found that RNA polymerase II C-terminal domain can phase-separate in vitro and is required for polymerase clustering in vivo in human cells (3). We will investigate whether active genes are accompanied by condensates that contain nascent RNA and elongation and RNA processing factors. This project combines in vitro biochemistry with in vivo bioimaging using high-end microscopy. It also requires genome engineering by CRISPR/Cas9.

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(1) Schwalb B, Michel M, Zacher B, Frühauf K, Demel C, Tresch A, Gagneur J, Cramer P.
TT-seq maps the human transient genome.
Science. 2016 Jun 3; 352(6290):1225-8.

(2) TT-seq captures enhancer landscapes immediately after T-cell stimulation.
Michel M, Demel C, Zacher B, Schwalb B, Krebs S, Blum H, Gagneur J, Cramer P.
Mol Syst Biol. 2017 Mar 7;13(3):920.

(3) RNA polymerase II clustering through carboxy-terminal domain phase separation.
Boehning, M. et al.:
Nature Structural and Molecular Biology 25 (9), S. 833 - 840 (2018)