Genetically encoded molecular tools for H 2 O 2 imaging and manipulation

Abstract

Synthetic biology approaches in modern biosciences allow obtaining living systems with new properties by trans-species and even trans-kingdom transfer of molecular machines. Examples are optogenetics and thermogenetics, genome editing by GRISPR-Cas systems, fluorescent proteins and biosensors. After 200 years from discovery of hydrogen peroxide by Thenard, we now use synthetic biology principles to study functions of H2O2 in biological systems. Tools that we have include genetically encoded fluorescent biosensors for H2O2 based on fluorescent proteins from hydrozoan and anthozoan species and bacterial sensing domains, and metabolic engineering tools that are yeast and prokaryotic enzymes with unique capabilities placed in a context of an animal cell. This allow us to precisely monitor and modulate H2O2 levels inside compartments and sub-compartments of the living cells, in a cell- and tissue-specific way. In my talk I will show how antioxidant systems of the cell maintain engineered intracellular H2O2 gradients and define intercompartment H2O2 traffic. I will also give an overview of several new metabolic engineering tools that allow control over key redox parameters in the living cells.