Karl Deisseroth


Karl Alexander Deisseroth is the D. H. Chen Professor of Bioengineering and of Psychiatry and Behavioral Sciences at Stanford University. He is known for creating and developing the technologies of CLARITY 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.

Education

Deisseroth earned his AB in biochemical sciences from Harvard University and his MD/PhD in neuroscience from Stanford University in 1998, and completed medical internship and psychiatry residency at Stanford Medical School.

Career

Deisseroth has led his laboratory at Stanford University since 2004, serves as an attending physician at Stanford Hospital and Clinics, and has been affiliated with the Howard Hughes Medical Institute since 2009. Between 2014 and 2019 he was a foreign Adjunct Professor at Sweden's Karolinska medical institute.

Research

Light-gated ion channels, optogenetics, and neural circuits of behavior
In 2005 Deisseroth's laboratory, including graduate students Edward Boyden and Feng Zhang, published the first demonstration of the use of microbial opsin genes encoding light-gated ion channels to achieve optogenetic control of neurons, allowing reliable control of action potentials with light at millisecond precision. Deisseroth named this field "optogenetics" in 2006 and followed up with optogenetic technology development work, leading to many applications including to psychiatry and neurology. In 2010, the journal Nature Methods named optogenetics "Method of the Year".
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. 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 his frequent collaborator Peter Hegemann and Miesenböck for "optogenetics, a technology that utilizes light to control cells in living tissues". 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 utilizing these opsins to develop optogenetics". 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. In 2019, Deisseroth, Hegemann, Boyden, and Miesenböck won the Warren Alpert Foundation Prize.. 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".
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 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, reviewed in. Two major prizes paid particular attention to Deisseroth’s work on elucidation of the structure and function of light-gated ion channels .
Deisseroth’s lab also achieved single-cell optogenetic control in living animals through a combination of optogenetics and high-resolution light guidance methods, including in behaving mammals.
Although the first peer-reviewed paper demonstrating activation of neurons with a channelrhodopsin was from his lab in mid-2005, Deisseroth has emphasized that many “pioneering laboratories around the world” were also working on the idea and published their papers within the following year; he cites Stefan Herlitze and Alexander Gottschalk/Georg Nagel who published their papers in late 2005, and Hiromu Yawo and Zhuo-Hua Pan who published their initial papers in 2006. Interestingly, Deisseroth also pointed out that an even earlier experiment had occurred and was published from 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. 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.
The majority
of Deisseroth’s publications have been focused on application of his methods to elucidate how mammalian survival-related behaviors like thirst and anxiety, whether adaptive or maladaptive, arise from the activity of specific cells and connections in neural circuitry. Several awards have specifically noted Deisseroth’s neuroscience discoveries in this way, separate from his contributions to channelrhodopsin structure or optogenetics. Deisseroth’s 2018 Kyoto Prize cited his "causal systems neuroscience", the 2013 Pasarow Prize was awarded to Deisseroth for "neuropsychiatry research"
, 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", the Redelsheimer Award from the Society for Biological Psychiatry was awarded to Deisseroth for "furthering the field's understanding of the neuroscience underlying behavior", and Deisseroth’s 2017 Fresenius Prize cited "his discoveries in optogenetics and hydrogel-tissue chemistry, as well as his research into the neural circuit basis of depression".
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.
The first step in this direction was hydrogel-tissue chemistry in which "specific classes of native biomolecules in tissue are immobilized or covalently anchored ". Then, "precisely timed polymerization causing tissue-gel hybrid formation is triggered within all the cells across the tissue in an ordered and controlled process to ultimately create an optically and chemically accessible biomolecular matrix". In 2013, Deisseroth was senior author of a paper describing the initial form of this method, called CLARITY ; this method makes biological tissues such as mammalian brains translucent and accessible to molecular probes.
CLARITY
has been widely used
and many variants on the basic HTC backbone have been developed in other labs as well since 2013.
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”. For example, HTC variants now enable improved anchoring and amplification of RNA, reversible size changes, and in situ sequencing.
Several major prizes have cited Deisseroth’s development of HTC, including 1) 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” ; 2) 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” ); 3) the 2013 Premio Citta di Firenze ); 4) 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” ); 5) the 2015 Dickson Prize in Medicine ); and 6) 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."
In 2020 Deisseroth and Zhenan Bao described another chemical synthesis of functional material in situ, this time with cell-specific chemistry. Their genetically-targeted chemical assembly method instructs specific living cells to guide chemical synthesis of functional materials. The initial GTCA created electrically functional polymers at the plasma membrane, and the team noted “Distinct strategies for the targeting and triggering of chemical synthesis could extend beyond the oxidative radical initiation shown here while building on the core principle of assembling within cells genetically and anatomically targeted reactants, catalysts, or reaction conditions.”
In 2019 Deisseroth was elected to the US National Academy of Engineering, completing membership in all three US National Academies.

Honors and awards