Awards for best BMLS theses go to Maja Klaus and Dennis Vettkötter
16 July 2020. BMLS is pleased to announce the results of the selection process for the best BMLS PhD thesis and best BMLS master thesis completed in 2019. Maja Klaus won the Josef Buchmann Doctoral Excellence Award for her PhD thesis on “Engineering of modular polyketide synthases”. Dennis Vettkötter won the Josef Buchmann Master Excellence Award for his master thesis “Development of optogenetic tools for clustering of synaptic vesicles”.
Maja Klaus conducted her PhD project in the lab of Martin Grininger. She analyzed a class of enzymes that produces polyketide secondary metabolites which often exhibit high biological activities. Examples are the antibiotics erythromycin, rifamycin and tetracyclin, immunosuppressants such as rapamycin, and cholesterol lowering agents such as lovastatin. These enzymes, called polyketide synthases (PKSs), are large megaenzymes which occurr in bacteria, fungi and plants. They produce polyketides by an elegant mechanism and often exhibit a modular architecture in which the order of modules defines the composition of the final product, which is assembled via the step-wise addition of simple building blocks like with an assembly line. Modular polyketide synthases are exciting targets for rational design approaches, as the exchange of whole modules or single domains of the protein complex might yield a new product with altered biological activities. During her PhD project, Maja pursued different engineering approaches using the polyketide synthase DEBS, which normally produces the macrolide precursor of the antibiotic erythromycin, to create novel polyketide synthases. She developed and established new design strategies to guide the assembly of novel multi-module enzyme cascades. The in-depth biochemical characterizations and structural elucidation and modelling techniques performed in this thesis led not only to a deeper understanding of mechanistic and structural features of this class of megaenzymes, but uncovered the limitations of hitherto promising PKS engineering approaches. It led to the identification of crucial aspects that need to be improved to allow the use of these enzyme complexes in the development of novel antibiotics in the near future.
Dennis Vettkötter did his master project in the lab of Alexander Gottschalk. In this project, Dennis generated a highly useful new neuronal silencing tool, based on an entirely new mechanism, which will be useful in all branches of neurobiology research, and in many model organisms. His tool will facilitate the analysis of how individual nerve cells, or groups of neurons, function in computations in the brain, and in generating behaviour in animal models. Furthermore, it may allow the modelling of diseases in which malfunction of certain neuron types is causative. Dennis used optogenetics to achieve this goal. This methodology uses light-sensitive proteins that are genetically encoded and can thus be targeted to certain cell types. The efficiency of his new tool was evaluated at the level of behaviour and light activation significantly reduced the swimming locomotion of the C. elegans worms by 80% within a few seconds. After receiving his MSc, Dennis started a PhD project with Alexander Gottschalk.
We congratulate Maja and Dennis on their achievements and wish them all the best for the future. For further information about these research areas just visit the websites of the Grininger lab and the Gottschalk lab.