He is known for creating and developing the technologies of hydrogel-tissue chemistry (e.g., CLARITY, STARmap) and optogenetics, and for applying integrated optical and genetic strategies to study normal neural circuit function, as well as dysfunction in neurological and psychiatric disease.
In 2021, he authored a book titled Projections: A Story of Human Emotions, published by Random House, where he explores the origins of human emotions through personal encounters with patients.[3]
Research
Light-gated ion channels, optogenetics, and neural circuits of behavior
Deisseroth named this field "optogenetics" in 2006 and followed up with optogenetic technology development work leading to many applications, including psychiatry and neurology. In 2010, the journal Nature Methods named optogenetics "Method of the Year".[4]
For developing optogenetics, Deisseroth received in 2010 the Nakasone Award; in 2013 the Lounsbery Award and the Dickson Prize in Science; in 2014 the Keio Medical Science Prize; and in 2015 the Albany Prize, Lurie Prize, Dickson Prize in Medicine, and Breakthrough Prize in Life Sciences.[5] He also received the 2015 BBVA Foundation Frontiers of Knowledge Award in Biomedicine, jointly with Edward Boyden and Gero Miesenböck. In 2016, Deisseroth received the Massry Prize along with Peter Hegemann and Miesenböck for "optogenetics, a technology that utilizes light to control cells in living tissues".[6] In 2016, the Harvey Prize from the Technion in Israel was awarded to Deisseroth and Hegemann "for their discovery of opsin molecules, involved in sensing light in microorganisms, and their pioneering work in using these opsins to develop optogenetics".[7] Deisseroth was then awarded Japan's highest private prize, the Kyoto Prize, in 2018, for "his discovery of optogenetics and the development of causal systems neuroscience", becoming the youngest recipient of the award to date.[8][9] In 2019, Deisseroth, Hegemann, Boyden, and Miesenböck won the Warren Alpert Foundation Prize.[10] Finally in 2020, Deisseroth received the Heineken Prize from the Royal Netherlands Academy of Arts and Sciences, "for developing optogenetics — a method to influence the activity of nerve cells with light".[11]
Deisseroth is also known for achieving insight into the light-gated ion channel pore of channelrhodopsin itself, through his teams' initial high-resolution crystal structures of cation and anion-conducting channelrhodopsins[12][13][14] and through a body of structure/function work discovering mechanisms of channelrhodopsin kinetics, ion selectivity, and color selectivity, together with his frequent collaborator Peter Hegemann.[15] Two major prizes paid particular attention to Deisseroth's work on elucidation of the structure and function of light-gated ion channels—the 2016 Harvey Prize to Deisseroth and Hegemann for the "discovery of opsin molecules, involved in sensing light in microorganisms, and for the pioneering work in utilizing these opsins to develop optogenetics",[7] and the 2018 Gairdner Award, which noted "his group discovered the fundamental principles of the unique channelrhodopsin proteins in molecular detail by a wide range of genomic, biophysical, electrophysiological and structural techniques with many mutants in close collaboration with Peter Hegemann").[16]
Although the first peer-reviewed paper[17] demonstrating activation of neurons with a channelrhodopsin was from his lab in mid-2005, Deisseroth has emphasized that many "pioneering laboratories around the world"[18] were also working on the idea and published their papers within the following year; he cites Stefan Herlitze[19] and Alexander Gottschalk/Georg Nagel,[20] who published their papers in late 2005, and Hiromu Yawo[21] and Zhuo-Hua Pan,[22] who published their initial papers in 2006 (Pan's early observation of optical activation of retinal neurons expressing channelrhodopsin would have occurred in August 2004, according to Pan,[23] about a month after Deisseroth's initial observation). Deisseroth has published the notebook pages from early July 2004 of his initial experiment showing light activation of neurons expressing a channelrhodopsin.[24] Deisseroth also pointed out[24] that an even earlier experiment had occurred and was published by Heberle and Büldt in 1994, in which functional heterologous expression of a bacteriorhodopsin for light-activated ion flow had been published in a non-neural system (yeast).[25] Optogenetics with microbial opsins as a general technology for neuroscience was enabled only by the full development of versatile strategies for targeting opsins and light to specific cells in behaving animals by taking advantage of Cre-lox neurogenetics developed by Joe Tsien in the 1990s.[24][26][27]
Other awards:
Deisseroth's 2018 Kyoto Prize cited his "causal systems neuroscience".[28]
The 2013 Pasarow Prize[29] was awarded to Deisseroth for "neuropsychiatry research".[30]
The 2013 Premio Citta di Firenze was given to Deisseroth for "innovative technologies to probe the structure and dynamics of circuits related to schizophrenia, autism, narcolepsy, Parkinson's disease, depression, anxiety and addiction".[31]
The Redelsheimer Award from the Society for Biological Psychiatry was awarded to Deisseroth for "furthering the field's understanding of the neuroscience underlying behavior".[32]
Deisseroth's 2017 Fresenius Prize[33] cited "his discoveries in optogenetics and hydrogel-tissue chemistry, as well as his research into the neural circuit basis of depression".[34]
Chemical assembly of functional materials in tissue
Deisseroth is known also for a separate class of technological innovation. His group has developed methods for chemical assembly of functional materials within biological tissue. This approach has a range of applications, including probing the molecular composition and wiring of cells within intact brains.
In 2013, Deisseroth was senior author of a paper describing the initial form of this method, called CLARITY (with a team including first author postdoctoral fellow in his lab Kwanghun Chung,[35] and neuroscientist Viviana Gradinaru).[36] This method makes biological tissues, such as mammalian brains, translucent and accessible to molecular probes.[37]
CLARITY[38]
has been widely used,[39]
and many variants on the basic HTC backbone have been developed in other labs as well since 2013 (reviewed in[40]).
A key feature of HTC is that the hydrogel-tissue hybrid "becomes the substrate for future chemical and optical interrogation that can be probed and manipulated in new ways".[40] For example, HTC variants now enable improved anchoring and amplification of RNA, reversible size changes (contraction or expansion), and in situ sequencing (reviewed in[40]). In particular, STARmap is an HTC variant that allows three-dimensional cellular-resolution transcriptomic readouts within intact tissue.[41][42][43])
Several major prizes have cited Deisseroth's development of HTC, including:
The 2017 Fresenius Prize "for his discoveries in optogenetics and hydrogel-tissue chemistry, as well as his research into the neural circuit basis of depression".[44][33][45]
The 2015 Lurie Prize in Biomedical Sciences "for leading the development of optogenetics, a technology for controlling cells with light to determine function, as well as for CLARITY, a method for transforming intact organs into transparent polymer gels to allow visualization of biological structures with high resolution and detail".[46]
The Redelsheimer Award for "optogenetics, CLARITY, and other novel and powerful neural circuit approaches in furthering the field's understanding of the neuroscience underlying behavior".[47]
The 2020 Heineken Prize for Medicine, for "developing optogenetics — a method to influence the activity of nerve cells with light — as well as for developing hydrogel-tissue chemistry, which enables researchers to make biological tissue accessible to light and molecular probes."[49]
^Deisseroth KA, Chung K. 2015. Methods and compositions for preparing biological specimens for microscopic analysis. www.google.com/patents/US20150144490. Filing date: March 13, 2013. US Patent Appl. No. US20150144490
^Deisseroth KA, Gradinaru V. 2014. Functional targeted brain endoskeletonization. www.google.com/patents/US20140030192. Filing date: January 26, 2012. US Patent Appl. No. US20140030192.
