University University of Groningen (UG)
Institute and/or group Groningen Biomolecular Sciences & Biotechnology Institute (GBB)
Advisors Prof. dr. Bert Poolman (UG), Prof. dr. Dirk Slotboom (UG)
oLife Research Areas II. Defining properties and synthesis of Life, from the molecular to the biosphere level
III. Modelling, predicting and steering of Life
Start date August 1, 2020

Profile of the fellow

After becoming a technical assistant, Sebastian found a passion for research and studied pharmacy at the University of Munich, Germany. In his following doctoral research, he became interested in the specialized metabolism of microorganisms, which gives rise to a wide array of natural products. In this field, he joined the group of Michael Müller in Freiburg, Germany, where he focused on finding new oxidative enzymes that catalyze unusual reactions such as phenol coupling. He also identified the genes that are responsible for the production ibotenic acid, the main toxin of the fly agaric. Now, joining the oLife Programme, he will dedicate his work to study ancestral forms of secondary active transporters.

Ancestral neurotransmitter transporters

Neurotransmitter transporters, also called SLC6, are a family of secondary active transporters that underwent an impressive diversification during evolution. Thus, 20 different transporters belonging to this group are found in humans. Their substrates include many amino acids and almost all neurotransmitters – hence the name of the family.

The diverse specificities must have arisen from one ancestral SLC6 transporter, which was likely present in the last universal common ancestor. This diversification of function can be reconstructed in the form of a phylogenetic tree, to determine the path and sequence of diversity evolution. To test the phylogeny, ancestral SLC6 protein sequences can be inferred. Thereafter, the enzymes can be “resurrected” by synthesizing the ancestral genes, which are then expressed heterologously. The resurrected transporters can then be subjected to biochemical analysis, determining their transport specificities. This way, the path of evolution leading to the diverse transporters can be delineated to pinpoint the necessary changes to produce this diversity. Thus, ancestral functions of SLC6 transporters can be “evolved back”. This will furthermore facilitate their use in present-day applications, such as the creation of synthetic cells.