PhD Student, EsCat ITN Graduate School
Scientific Career and Education
- 04/2017 PhD research at the Institute for Evolution and Biodiversity, University of Münster
- 2014-2017 Master Molecular Life Sciences, Specialisation: Biological Chemistry, Wageningen University, The Netherlands
- 2010-2014 Bachelor Molecular Life Sciences, Wageningen University, The Netherlands.
- Enzyme evolution
- Enzyme promiscuity
- Ancestral reconstruction
- Directed evolution
- Directed evolution in the lab can emulate natural evolution, which over a course of a few billion years has resulted in a wide variety of protein structures carrying out many functions with unrivalled efficiency. However, the combination of mutations needed for large improvements cannot always be reached due to the occurrence of general loss of function or epistatic ratchets. To avoid evolutionary dead ends knowledge of the fitness landscape around proteins would be helpful. Several ancestral sequences of the alkaline phosphatase (AP) superfamily have been inferred, reconstructed and their substrate specificity profiles have been mapped and nodes were function diverged have been identified. These substrate specificity profiles suggest a charge in primary function that is the result of a shift in specificity rather than de novo invention of a novel activity. The main aim of my project is to explore the sequence space around ancestral and extant members of the AP superfamily using directed evolution approaches, connecting their ‘fitness parameters’, i.e. the interplay of activity, stability and epistasis to the shape of the fitness landscape of their local sequence space. This should provide quantitive insight into which properties are most important in determining the evolvability of enzymes.
- Bert van Loo , Magdalena Heberlein , Philip Mair , Anastasia Zinchenko , Jan Schüürmann , Bernard D G Eenink , Josephin M Holstein, Carina Dilkaute, Joachim Jose , Florian Hollfelder, Erich Bornberg-Bauer High-Throughput, Lysis-Free Screening for Sulfatase Activity Using Escherichia coli Autodisplay in Microdroplets ACS Synthetic Biol, 8 (12), 2690-2700 Online Access
- Patrick Buchholz, Bert van Loo, Bernard Eenink, Erich Bornberg-Bauer, Jürgen Pleiss Ancestral sequences of a large promiscuous enzyme family correspond to bridges in sequence space in a network representation J. R. Soc. Interface.182021038920210389 Online Access