Credit: Sahtoe group. Copyright: Hubrecht Institute.

Sahtoe: Protein structure, mechanism and design

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The Sahtoe group designs novel protein molecules to uncover the structural and mechanistic basis of life.

Life on earth is for a large part enabled by proteins. These molecules control processes ranging from metabolism to gene regulation and often form tightly regulated complexes that harbor catalytic and/or allosteric activity. Such sophisticated complexes can harvest light, eliminate pathogens or repair DNA damage. The Sahtoe lab aims to design novel protein systems that exhibit such sophisticated functions from the ground up. This allows us to understand the molecular basis of natural protein function, and enables us to design novel protein systems with functionalities that are not observed in nature and can be used for biomedical and biotechnological applications.

Probing epigenetics with protein design

The genetic information of eukaryotes is carefully organized in chromatin where DNA is condensed through interactions with specialized DNA binding proteins. These proteins together with chemical modifications of chromatin control the expression of genes epigenetically i.e. without changing the DNA sequence and therefore control virtually all processes in eukaryotes. Because epigenetic  processes are often deregulated in disease it is important to study the molecular epigenetic mechanisms in detail. We design novel proteins that interact with native chromatin factors in order to study these mechanisms.

Design of advanced protein functions

Molecular recognition, catalysis and allostery are hallmarks of life that enable the advanced protein functions observed in the natural world. These functions are often subject to multiple layers of regulation frequently through protein-protein interactions. We create such complex systems from the ground up and measure their activities in vitro in order to obtain a detailed understanding of the underlying biochemical and biophysical mechanisms. Our insights can be used to understand natural protein systems. The comprehensive knowledge that we obtain will allow for the design of next generation therapeutics that go beyond simple binding but can respond to their molecular environments and limit off target effects.