Project 1

Structural basis of two-component system signaling

Prof. Dr. Ute Hellmich (main supervisor)
Biostructural Interactions Group, Friedrich-Schiller University Jena
Prof. Dr. Sarah O’Connor/ (co supervisor)
Department of Natural Product Biosynthesis, Max Planck Institute for Chemical Ecology

As bacteria explore new habitats, go to war with competitors or collaborate against common enemies, they rely heavily on intra- and interspecies communication and precise molecular scouting of their environment. So-called two-component systems (TCS) are essential molecular communication modules in quorum sensing and enable bacteria to probe and react to environmental cues (e.g. redox state, nutrients, pH). Prototypical TCS consist of a membrane-bound histidine kinase (HK) with an extracellular sensor domain, a transmembrane region, and an intracellular kinase domain as well as a soluble response regulator that acts as a dedicated transcription factor. Despite their importance in all areas of intra- and interspecies signalling, the molecular basis of TCS-activation and regulation, as well as the structural interplay of the three elements (signal molecule-histidine kinase- response regulator) are not well understood.

Project description:  
In this project, you will use state of the art structural, biophysical and biochemical approaches to determine how a two component sensing system works. Specifically, you will   use these methods to elucidate the allosteric pathways between the histidine kinase’s sensor and kinase domain. Embedded in a highly interdisciplinary team, you will explore how bacterial and plant-derived signalling molecules activate and shape two component system signalling. Methods include protein biochemistry, microbiology, functional assay development, NMR spectroscopy, cryo-electron microscopy and/or X-ray crystallography, natural product extraction and analysis and molecular dynamics simulations.

Candidate profile:  
We seek a dedicated team player enthusiastic about the structure, function and dynamics of membrane proteins. Successful candidates will have an MSc in Biochemistry, Chemistry, Molecular Biology, Biophysics or a related discipline. Prior experience with protein purification, molecular biology and/or structural biology methods is an advantage. Proficiency in English (writing and oral) is necessary.

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