Beschreibung: |
Ever wondered what lava lamps and phase separation can teach us about chromatin regulation and gene expression?
A fascinating recent development in biology is the
realization that cells contain compartments with liquid-
like properties. These are neither membrane-bound
organelles nor structurally defined protein complexes, but
rather resemble ‘condensates’ formed by the demixing of
concentrated proteins from the surrounding cellular milieu. The underlying phenomenon is called phase separation and is observed in daily life, such as the separation of oil and vinegar in salad dressings or in lava lamps, as shown in the
picture.
We are excited about exploring the molecular principles and function of phase separation in the context of our favorite lab topic – chromatin and transcription. Our recent work has uncovered a role of phase separation in creating liquid-like reaction chambers for histone ubiquitination (Gallego L.D.*, Schneider M.*, Mittal, C.* et al.: Nature, 2020). Specifically, we found that the E3 ubiquitin ligase Bre1 interacts with Lge1, an intrinsically disordered protein, which promotes the phase separation of the ubiquitination machinery into enzymatically hyperactive condensates. We now aim to understand when, where and how these condensates form in cells, whether and how they move along chromatin and ultimately, how aberrant condensates may lead to disease when perturbing the flow of genetic information.
We are looking for an energetic, highly motivated student interested in exploring fundamental mechanisms in chromatin biology. You will employ biochemistry and microscopy approaches to understand the role of ‘lava-lamp phenomena’ during transcription at the single-molecule level. If accepted, you will also receive a stipend during your thesis.
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