The 2021 Albert Lasker Basic Medical Research Award recognizes Dieter Oesterhelt, Peter Hegemann, and Karl Deisseroth for the discovery of light-sensitive microbial proteins that can activate or silence individual brain cells and for their use in developing optogenetics—a revolutionary technique for neuroscience.

The 2026 Nobel Prize in Medicine has been awarded to Karl Deisseroth, Peter Hegemann, and Georg Nagel for their groundbreaking work on optogenetics, a revolutionary technique that allows precise control of specific neurons in living brains using light pulses. The discovery builds on decades of research beginning with the study of Chlamydomonas algae, which naturally respond to light through a protein called channelrhodopsin. In the 1990s, Hegemann and Nagel identified this light-sensitive protein in algae, which contains retinaldehyde that changes shape when exposed to light, opening ion channels and generating electrical signals. Deisseroth, at Stanford University, realized this protein could be used to control neurons. In 2005, he successfully inserted channelrhodopsin-2 into neurons, enabling them to respond to blue light, effectively creating a light-controlled 'switch' for brain cells. This breakthrough allowed researchers to activate or inhibit specific neurons with unprecedented precision, transforming neuroscience research. Unlike previous methods that used broad drugs or electrodes, optogenetics enables targeted manipulation of neural circuits, allowing scientists to map brain functions with remarkable detail. Applications include identifying neural circuits involved in depression, Parkinson's disease, schizophrenia, anxiety, addiction, memory, and autism. Early clinical trials are exploring optogenetics for retinal diseases, where light-sensitive proteins are introduced into remaining retinal cells to restore partial vision. The technique has also shown potential for use in cardiac and pancreatic cells, suggesting future applications in various medical fields. Deisseroth, a father of three, was preparing sandwiches for his children when he received the Nobel call, illustrating the human side of scientific achievement. His wife, Michelle Monje-Deisseroth, is also a prominent neuroscientist at Stanford, specializing in pediatric brain tumors. The Nobel Committee highlighted how optogenetics has revolutionized brain research, comparing it to CRISPR's impact on genetics, and enabling researchers to 'map' the brain in ways previously unimaginable.

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Read the full paper: Quantifying the influence of contraction history on ex vivo bladder mechanics using optogenetics

To create a tool to block autophagy rapidly, we leveraged a previously described truncation mutant of the key autophagy SNARE protein, STX17, which lacks the N terminus and acts as a dominant negative (DN)30. Previously, Uematsu et al.30 showed that 2 days of expression of myc-STX17ΔNTD blocks fusion of autophagosomes with lysosomes and inhibits autophagy, as evidenced by LC3-II accumulation. To leverage optogenetics to manipulate autophagy with light, we fused STX17ΔNTD to the photoactivatable protein hybrid LOV (hLOV1)32, which we engineered to cage a tobacco etch virus (TEV) protease recognition (tevS) site33 that is only accessible after a light-induced conformational change in hLOV1. To ensure equal expression, the TEV protease is transcribed from the same promoter and separated with a p2A consensus motif to enable ribosome skipping and allow for eukaryotic polycistronic RNA processing of both ASAP and TEV protease. The ASAP fusion construct is engineered such that it is targeted to the endoplasmic reticulum (ER) via an N-terminal IgK-leader sequence. The construct includes a PDGFR single-pass transmembrane (TM)34 domain designed to anchor the protein to the ER. In this configuration, the photoactivatable hLOV1 domain, the TEV protease cleavage site (tevS), and the effector STX17∆NTD are presented on the cytoplasmic...