INTRODUCTION

The Shaw Prize in Life Science and Medicine 2020 is awarded in equal shares to Professor Gero Miesenböck, Professor Peter Hegemann and Professor Georg Nagel for the development of optogenetics, a technology that has revolutionised neuroscience.

Understanding the brain is a daunting challenge. Each of the many billions of nerve cells in the human brain may make thousands of contacts with other neurons, resulting in an astronomical number of synaptic connections. Thanks to the discoveries of the Shaw Life Science Awardees for 2020, we now have the tools needed to visualise and precisely control specific neural networks in the brain of an animal. These discoveries presage a golden age of exploration of the mysteries of cognition and emotion with potential applications in psychiatric disorders that are only now being defined at the level of genes and cells.

Synopsis

“In two decades, optogenetic control of neuronal activity has developed from a far-fetched idea to a widely used technology. My lecture will recount how this happened, drawing on the earliest and latest results from my lab. To illustrate what is now possible, I will present new insights into the regulation and function of sleep. Optogenetics has allowed us to pinpoint neurons whose sleep-inducing activity switches on as sleep deficits accrue, revealed how this activity switch works, and furnished a molecular interpretation of sleep pressure and the mechanisms underlying its accumulation and discharge.”
by Professor Gero Miesenböck

“The long research on microbial photobiology is the foundation of the hundreds of microbial sensory photoreceptors that are currently used to study the brain with light. Especially the channelrhodopsins from microalgae as Chlamydomonas allow to activate and inactive selected neuronal cells of large networks by a precise control of the membrane voltage and to shape developmental and learning processes. The future perspectives are to extend this toolbox towards a light-controlled enzymology, transcription, and translation in order to understand the brain function including our thinking, creativity, emotions, dysfunctions and dreams.”
by Professor Peter Hegemann

“The discovery of Bacteriorhodopsin (BR) 50 years ago was the kickoff to unearthing an incredible treasure of microbial rhodopsins with different functions: light-sensitive ion transport or enzymatic activity. Heterologous expression and characterisation in animal cells – first with BR – tremendously advanced our understanding of these proteins.

This approach brought into the light the widely used optogenetic tool Channelrhodopsin-2 (ChR2), a light-gated cation channel. ChR2 is still the most popular optogenetic tool, especially the mutant H134R, introduced in 2005. After the demonstration of ChR2 as tool for membrane depolarisation, the light-activated chloride pump Halorhodopsin was the first optogenetic tool for membrane hyperpolarisation. But in both cases relatively high light intensities are necessary. The mutant ChR2/XXL with strongly improved expression and slow photocycle enables depolarisation and light-manipulation of living fruit flies at much lower light intensity. With the strictly light-regulated guanylyl cyclase Cyclop we characterised the first microbial rhodopsin with 8 transmembrane helices.

Plant optogenetics lagged behind but recently we generated transgene tobacco plants which express highly functional anion-channelrhodopsin in the plasma membrane. These plants grow normally in red light but show strong effects upon illumination with blue or green light.”
by Professor Georg Nagel