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New Biological Frontiers Illuminated by Molecular Sensors and Actuators Monday Speaker Abstracts
Photodissociable Photoswitchable Dimeric Fluorescent Proteins Enable Optical Control of
Kinase Activity
Michael Lin
Stanford University, USA.
About twenty years ago, the cloning of fluorescent proteins catalyzed a revolution in biological
research. With ideal characteristics as tags and as components of reporter proteins, fluorescent
proteins enabled visualization of biological processes in living cells, with spatial detail and in
real time. A second optical revolution is now in the making, with ongoing efforts to use light to
control rather than to sense biological activities. While examples exist of adapting natural
photoregulatory to regulate biology in mammalian cells, this approach has limitations. We have
been exploring the hypothesis that fluorescent proteins can be engineered into ideal
photoregulatory proteins as well. We recently engineered the photoswitchable fluorescent protein
Dronpa into a photodissociable tetramer, then developed a design for caged proteins in which
two copies of Dronpa are fused to a protein of interest so that tetramerization blocks protein
activity and photodissociation activates it. We will present recent advances in improving the
performance of photodissociable Dronpa domains and in generalizing the caged protein design to
an important class of regulatory proteins, the kinases.