Thesis Award

Melina Baur

In her bachelor thesis, Melina Baur used a tetracycline-binding aptamer to control gene expression in eukaryotes at the posttranscriptional level. Integration of the switch led to control of alternative splicing of not only synthetic but also native sequences. Further testing showed that the switch can be fine-tuned and therefore adapted to specific applications. Overall, this work expands the synthetic biology toolbox for controlling eukaryotic gene expression at the level of splicing.

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Tobias Probanowski

In his master thesis, Tobias Probanowski developed a new modular approach for the systematic construction and engineering of recombinant protein nanopore assemblies with novel properties and functions in E. coli. This approach involved the recombination of different pore-forming transmembrane domains with ring-shaped oligomeric protein scaffolds via protein linkers. The resulting variants were characterized using the newly developed FuN screen, which allows for quick and thorough assessment previously only possible using technically challenging and low throughput biophysical methods. In synthetic biology, such nanopore assemblies could find a wide range of potential applications both in live cells and in vitro.

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Stefania Carrara

In her dissertation, Dr. Stefania Carrara developed novel multispecific antibodies with immune cell modulating functions and established new methodologies for the optimization of antibody drug discovery workflows. These included the design of a bidirectional vector system for mammalian antibody production and a streamlined yeast surface display-based screening procedure. Furthermore, bi- and multispecific molecules engaging different immune cells were generated, resulting in targeted and efficient in vitro tumour cell killing. The tetraspecific antibodies contain a built-in risk mitigation strategy for commonly observed adverse effects with this class of antibody molecules, which may overcome limitations of existing therapies and pave the way for new multispecific antibody formats.

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Ron Endruszeit

“In his bachelor thesis Ron Endruszeit tested the extend to which membrane proteins of the autotransporter family enable efficient surface display of complex fusion proteins in E. coli, and demonstrated the suitability of the system for protein-interaction screening by immobilization of binding partners on the cell surface. From the repertoire generated via the cloning strategy iFLinkC, a dependence of the protein-target interaction on the properties of the varied linkers could be concluded. In the future, the system should enable the fast and customized selection and isolation of protein variants from cell libraries.”

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Sarah Schmitt

In her master's thesis, Sarah Schmitt worked on the recombinant modification of nanopores. With the help of protein engineering, nanopores can not only be better understood in terms of how they function, but their properties can also be modified, paving the way for biotechnological use. Furthermore, a native nanopore was modified to combine its own perforation properties with regulatory and sensory features.

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Jan Bogen

In his dissertation, Dr Jan Bogen developed a variety of new methods for the generation, screening and engineering of tumour-specific antibodies. These included a novel method for the construction of immune libraries based on bidirectional vector systems, an approach for the rapid and effective humanisation of therapeutic drug candidates and for the generation of biparatopic antibodies. The molecules isolated in this work were adapted and optimised so that they could be combined into a trispecific, multifunctional antibody. This was able to prevent both the growth of cancer cells and their masking from the immune system, and at the same time mediated the attack of immune cells on the tumour cells. This molecule is thus unique in its mode of action and paves the way for new therapeutic approaches in the future.

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Theresa Wörmann

In her bachelor thesis, Theresa Wörmann constructed a fluorescent protein sensor against the biotechnologically relevant macrolide rapamycin and successfully applied it to quantitatively measure the flux of rapamycin across the cell membrane of E.coli in dependence on pore-forming membrane peptides. The bachelor thesis opens up a novel approach to systematically investigate the permeability of biotechnologically relevant products – an important but largely overlooked aspect in industrial biotechnology.

Christoph Reich

In his bachelor thesis, Christoph Reich developed a neural network – technically a generative adversarial network – to synthesize temporal multi-domain image sequences and showcased it with short time-lapse fluorescence microscopy imagery of yeast. These in silico simulations capture underlying biophysical factors and time dependencies, such as cell morphology, growth, physical interactions, as well as the intensity of a fluorescent reporter protein. The thesis is a first step towards completely in silico experimentation and in the future, this approach may complement and augment classical experimentation and mathematical modeling. The thesis is available on arXiv (https://arxiv.org/abs/2103.11834), along with a follow-up paper recently accepted to MICCAI 2021 (https://arxiv.org/abs/2106.08285).

Alexander Gräwe

In his doctoral thesis, Alexander Gräwe developed fundamental strategies for the construction of molecular sensory systems. This included novel approaches for the systematic construction of molecular switches, as well as, in collaboration with chemists and material scientists, a process for functionalising nanoporous films with customised receptors. The developed methods are to be used in medical diagnostics or in environmental monitoring.