DAAD scholarships

In response to the worldwide antibiotics crisis, our lab is presently developing RNA-based antibiotics. Based on our expertise in targeted in vitro selection (SELEX), we are developing RNA aptamers to efficiently kill pathogenic bacteria. These RNA aptamers are obtained by a selection process from large combinatorial libraries, bind their target molecule with high affinity and specificity and inhibit their activity. Targets of interest are proteins that lead to multidrug-resistance in germs of concern, for example the penicillin-binding protein 2a from Staphylococcus aureus. Ultimately, the aim is to establish a proof of concept for a new type of RNA therapeutics.

The Stein lab can host research projects in the field of protein engineering and synthetic biology. A particular emphasis is on engineering protein sensors, switches as well as diffusion and transport processes across cellular and biomimetic membranes while focussing on metabolites, drugs and other small molecules.

Applications for the envisaged protein technologies are diverse. For instance, protein sensors can be used for the real-time analysis of metabolites and drugs in both live cells and complex diagnostic samples. Similarly, protein switches can be applied to control molecular functions with exquisite specificity and temporal resolution. Further, sensors and switches can be used to build sense-and-respond circuits operating autonomously in live cells and intelligent (bio)materials. Finally, tailor-engineered transport processes across biological and biomimetic membranes can form part of sophisticated sensing and separation technologies.

Molecular Engineering endeavours are generally complemented by the development of dedicated enabling technologies (e.g. combinatorial DNA assembly methods, high-throughput screening systems and robotic automation) that are combined with high-resolution analytical methods (e.g. electrophysiological measurements in lipid bilayers and live cell fluorescence microscopy in microfluidics) to gain fundamental insight how artificially engineered proteins functions and ultimately facilitate the underlying construction process.

The project, titled Functional and structural characterization of FKBP-Hsp90-steroid hormone receptor complexes by large-scale, site-specific, in-cell photo-crosslinking aims to uncover key states and interaction partners of FKBP51, a significant target for conditions such as depression, obesity-induced diabetes, and pain.

The position is tailored for PhD candidates with an interest in biochemistry, molecular and chemical biology, especially those eager to apply their knowledge to drug discovery. Ideal candidates will hold a Master’s degree in life sciences or (bio)chemistry, with a strong background in molecular biology and protein biochemistry techniques.

Participants in this project will receive training in advanced molecular biology methods and benefit from dedicated mentorship within an interdisciplinary and international research group. The project is planned for a duration of 3+ years, with compensation aligned to E13/65%.

For further background, candidates are encouraged to review Baischew Engel et al., published in Nature Structural & Molecular Biology in 2023. Contact Prof. Felix Hausch or visit the group's webpage.

We seek a motivated PhD candidate to contribute to our research on the development and organisation of artificial cells into complex metastructures that mimic biological systems. The project focuses on enzymatically-synthesized hybrid polymer-lipid systems and dynamic transitions between membranised and coacervate-based architectures to create versatile synthetic cells. These constructs will be organised into higher-order tissue-like structures using assembly techniques, including microfluidics and stimuli-responsive elements, to enable adaptability and controlled interactions. The research further explores artificial symbiosis, integrating synthetic and natural cells for applications in tissue regeneration, drug delivery, and biomanufacturing. This interdisciplinary work bridges synthetic biology, polymer chemistry, and bioengineering to advance the design of adaptive, life-like materials.

Development of spatially structured and vascularized 3D human tissue models

Three-dimensional (3D) human tissue models generated in the laboratory represent versatile in vitro models for human disease studies, drug development and toxicology assessment. They have the potential to reduce animal testing and hold great promise for regenerative medicine. However, their routine application is hindered by several limitations of the current models. One critical limitation is the lack of control over the precise spatial arrangement of cell types. Another limitation of human tissue models with diameters of more than several hundred µm is the lack of a vascular system that transports oxygen, nutrients, and metabolic waste products to and from cells.

In natural human tissues, morphogen gradients steer the spatial development and maintenance of cell types. We have developed diffusion-based devices beyond the scale of microfluidic ones to regionalize human multicellular assemblies through concentration gradients of small bioactive molecules. Moreover, we harness the intrinsic morphogenetic capacity of vascular cells to generate a microvasculature in multicellular 3D human cell models. This process is supported by the integration of biomaterials into 3D cell cultures. To monitor cellular stages and positions in human tissue models, we have generated hiPSC fluorescent reporter lines by the CRISPR-Cas9 system.