Karl Deisseroth

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Karl Deisseroth
Karl Deisseroth by Christopher Michel 04.jpg
Deisseroth in 2022
Born (1971-11-18) November 18, 1971 (age 52)
Boston, Massachusetts, US
Alma mater Harvard University
Stanford University
Known for Optogenetics and Hydrogel-Tissue Chemistry (including CLARITY and STARmap)
Spouse Michelle Monje
AwardsNAMedi (2010)
NAS (2012)
NAE (2019)
W. Alden Spencer Award (2011)
Keio Medical Science Prize (2014)
Albany Medical Center Prize (2015)
BBVA Foundation Frontiers of Knowledge Award (2015)
Breakthrough Prize in Life Sciences (2016)
Kyoto Prize (2018)
Heineken Prize (2020)
Albert Lasker Award for Basic Medical Research (2021)
Louisa Gross Horwitz Prize (2022)
Japan Prize (2023)
Scientific career
Fields
Institutions Stanford University
Academic advisors Richard Tsien, Robert Malenka
Doctoral students Feng Zhang, Viviana Gradinaru
Website web.stanford.edu/group/dlab/index.html

Karl Alexander Deisseroth (born November 18, 1971) is an American scientist. He is the D.H. Chen Foundation Professor of Bioengineering and of psychiatry and behavioral sciences at Stanford University.

Contents

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 2019, Deisseroth was elected as a member of the US National Academy of Engineering for molecular and optical tools for his discovery and control of neuronal signals behind animal behavior in health and disease. He is also a member of the US National Academy of Sciences and the US National Academy of Medicine.

Education

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

Career

Deisseroth has led his laboratory at Stanford University since 2004.[ citation needed ] He serves as an attending physician at Stanford Hospital and Clinics and has been affiliated with the Howard Hughes Medical Institute (HHMI) since 2009. [1] [2] Between 2014 and 2019, he was a foreign Adjunct Professor at Sweden's Karolinska Medical Institute.[ citation needed ]

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:

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:

Honors and awards

Personal life

Deisseroth is married to neuroscientist Michelle Monje, with whom he has four children.[ citation needed ]

Related Research Articles

<span class="mw-page-title-main">Behavioral neuroscience</span> Field of study

Behavioral neuroscience, also known as biological psychology, biopsychology, or psychobiology, is the application of the principles of biology to the study of physiological, genetic, and developmental mechanisms of behavior in humans and other animals.

Channelrhodopsins are a subfamily of retinylidene proteins (rhodopsins) that function as light-gated ion channels. They serve as sensory photoreceptors in unicellular green algae, controlling phototaxis: movement in response to light. Expressed in cells of other organisms, they enable light to control electrical excitability, intracellular acidity, calcium influx, and other cellular processes. Channelrhodopsin-1 (ChR1) and Channelrhodopsin-2 (ChR2) from the model organism Chlamydomonas reinhardtii are the first discovered channelrhodopsins. Variants that are sensitive to different colors of light or selective for specific ions have been cloned from other species of algae and protists.

<span class="mw-page-title-main">Photostimulation</span>

Photostimulation is the use of light to artificially activate biological compounds, cells, tissues, or even whole organisms. Photostimulation can be used to noninvasively probe various relationships between different biological processes, using only light. In the long run, photostimulation has the potential for use in different types of therapy, such as migraine headache. Additionally, photostimulation may be used for the mapping of neuronal connections between different areas of the brain by “uncaging” signaling biomolecules with light. Therapy with photostimulation has been called light therapy, phototherapy, or photobiomodulation.

<span class="mw-page-title-main">Halorhodopsin</span> Family of transmembrane proteins


Halorhodopsin is a seven-transmembrane retinylidene protein from microbial rhodopsin family. It is a chloride-specific light-activated ion pump found in archaea known as halobacteria. It is activated by green light wavelengths of approximately 578nm. Halorhodopsin also shares sequence similarity to channelrhodopsin, a light-gated ion channel.

Retinylidene proteins, or rhodopsins in a broad sense, are proteins that use retinal as a chromophore for light reception. They are the molecular basis for a variety of light-sensing systems from phototaxis in flagellates to eyesight in animals. Retinylidene proteins include all forms of opsin and rhodopsin. While rhodopsin in the narrow sense refers to a dim-light visual pigment found in vertebrates, usually on rod cells, rhodopsin in the broad sense refers to any molecule consisting of an opsin and a retinal chromophore in the ground state. When activated by light, the chromophore is isomerized, at which point the molecule as a whole is no longer rhodopsin, but a related molecule such as metarhodopsin. However, it remains a retinylidene protein. The chromophore then separates from the opsin, at which point the bare opsin is a retinylidene protein. Thus, the molecule remains a retinylidene protein throughout the phototransduction cycle.

Light-gated ion channels are a family of ion channels regulated by electromagnetic radiation. Other gating mechanisms for ion channels include voltage-gated ion channels, ligand-gated ion channels, mechanosensitive ion channels, and temperature-gated ion channels. Most light-gated ion channels have been synthesized in the laboratory for study, although two naturally occurring examples, channelrhodopsin and anion-conducting channelrhodopsin, are currently known. Photoreceptor proteins, which act in a similar manner to light-gated ion channels, are generally classified instead as G protein-coupled receptors.

<span class="mw-page-title-main">Gero Miesenböck</span>

Gero Andreas Miesenböck is an Austrian scientist. He is currently Waynflete Professor of Physiology and Director of the Centre for Neural Circuits and Behaviour (CNCB) at the University of Oxford and a fellow of Magdalen College, Oxford.

Optogenetics is a biological technique to control the activity of neurons or other cell types with light. This is achieved by expression of light-sensitive ion channels, pumps or enzymes specifically in the target cells. On the level of individual cells, light-activated enzymes and transcription factors allow precise control of biochemical signaling pathways. In systems neuroscience, the ability to control the activity of a genetically defined set of neurons has been used to understand their contribution to decision making, learning, fear memory, mating, addiction, feeding, and locomotion. In a first medical application of optogenetic technology, vision was partially restored in a blind patient with Retinitis pigmentosa.

<span class="mw-page-title-main">Edward Boyden</span> American neuroscientist

Edward S. Boyden is an American neuroscientist at MIT. He is the Y. Eva Tan Professor in Neurotechnology, a faculty member in the MIT Media Lab and an associate member of the McGovern Institute for Brain Research. In 2018 he was named a Howard Hughes Medical Institute Investigator. He is recognized for his work on optogenetics. In this technology, a light-sensitive ion channel such as channelrhodopsin-2 is genetically expressed in neurons, allowing neuronal activity to be controlled by light. There were early efforts to achieve targeted optical control dating back to 2002 that did not involve a directly light-activated ion channel, but it was the method based on directly light-activated channels from microbes, such as channelrhodopsin, emerging in 2005 that turned out to be broadly useful. Optogenetics in this way has been widely adopted by neuroscientists as a research tool, and it is also thought to have potential therapeutic applications. Boyden joined the MIT faculty in 2007, and continues to develop new optogenetic tools as well as other technologies for the manipulation of brain activity. Previously, Boyden received degrees in electrical engineering, computer science, and physics from MIT. During high school, Boyden attended the Texas Academy of Mathematics and Science.

<span class="mw-page-title-main">Feng Zhang</span> Chinese–American biochemist

Feng Zhang is a Chinese–American biochemist. Zhang currently holds the James and Patricia Poitras Professorship in Neuroscience at the McGovern Institute for Brain Research and in the departments of Brain and Cognitive Sciences and Biological Engineering at the Massachusetts Institute of Technology. He also has appointments with the Broad Institute of MIT and Harvard. He is most well known for his central role in the development of optogenetics and CRISPR technologies.

<span class="mw-page-title-main">Peter Hegemann</span> German biophysicist

Peter Hegemann is a Hertie Senior Research Chair for Neurosciences and a professor of Experimental Biophysics at the Department of Biology, Faculty of Life Sciences, Humboldt University of Berlin, Germany. He is known for his discovery of channelrhodopsin, a type of ion channels regulated by light, thereby serving as a light sensor. This created the field of optogenetics, a technique that controls the activities of specific neurons by applying light. He has received numerous accolades, including the Rumford Prize, the Shaw Prize in Life Science and Medicine, and the Albert Lasker Award for Basic Medical Research.

Boris Valery Zemelman is an American neuroscientist who is one of the pioneers of optogenetics.

<span class="mw-page-title-main">Anion-conducting channelrhodopsin</span> Class of light-gated ion channels

Anion-conducting channelrhodopsins are light-gated ion channels that open in response to light and let negatively charged ions enter a cell. All channelrhodopsins use retinal as light-sensitive pigment, but they differ in their ion selectivity. Anion-conducting channelrhodopsins are used as tools to manipulate brain activity in mice, fruit flies and other model organisms (Optogenetics). Neurons expressing anion-conducting channelrhodopsins are silenced when illuminated with light, an effect that has been used to investigate information processing in the brain. For example, suppressing dendritic calcium spikes in specific neurons with light reduced the ability of mice to perceive a light touch to a whisker. Studying how the behavior of an animal changes when specific neurons are silenced allows scientists to determine the role of these neurons in the complex circuits controlling behavior.

<span class="mw-page-title-main">Georg Nagel</span>

Georg Nagel is a biophysicist and professor at the Department for Neurophysiology at the University of Würzburg in Germany. His research is focused on microbial photoreceptors and the development of optogenetic tools.

Ernst Bamberg is a German biophysicist and director emeritus of the Department of Biophysical Chemistry at the Max Planck Institute of Biophysics.

<span class="mw-page-title-main">Viviana Gradinaru</span> American neuroscientist and biomedical engineer

Viviana Grădinaru is a Romanian-American neuroscientist who is a Professor of Neuroscience and Biological Engineering at the California Institute of Technology. She develops neurotechnologies including optogenetics CLARITY tissue clearing, and gene delivery vectors. She has been awarded the Presidential Early Career Award for Scientists and Engineers and the National Institutes of Health Director's Pioneer Award. In 2019 she was a finalist for the Blavatnik Awards for Young Scientists. In 2020 she was awarded a Vilcek Prize for Creative Promise in Biomedical Science by the Vilcek Foundation.

Lisa Gunaydin is an American neuroscientist and assistant professor at the Weill Institute for Neurosciences at the University of California San Francisco. Gunaydin helped discover optogenetics in the lab of Karl Deisseroth and now uses this technique in combination with neural and behavioral recordings to probe the neural circuits underlying emotional behaviors.

Ilana B. Witten is an American neuroscientist and professor of psychology and neuroscience at Princeton University. Witten studies the mesolimbic pathway, with a focus on the striatal neural circuit mechanisms driving reward learning and decision making.

<span class="mw-page-title-main">Polina Anikeeva</span>

Polina Olegovna Anikeeva is a Russian-born American materials scientist who is a Professor of Material Science & Engineering as well as Brain & Cognitive Sciences at the Massachusetts Institute of Technology (MIT). She also holds faculty appointments in the McGovern Institute for Brain Research and Research Laboratory of Electronics at MIT. Her research is centered on developing tools for studying the underlying molecular and cellular bases of behavior and neurological diseases. She was awarded the 2018 Vilcek Foundation Prize for Creative Promise in Biomedical Science, the 2020 MacVicar Faculty Fellowship at MIT, and in 2015 was named a MIT Technology Review Innovator Under 35.

Alexander Gottschalk is Professor of Cellular and Molecular Neurobiology at the Goethe University in Frankfurt, Germany.

References

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  56. ↑ "2013 premio-citta-di-firenze".
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  60. ↑ "2013 Lounsbery Award".
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  62. ↑ Optogenetics earns Stanford professor Karl Deisseroth the Keio prize in medicine, Stanford, 2014
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  64. ↑ "2015 lurie-prize". Foundation for the National Institutes of Health. Archived from the original on September 1, 2015. Retrieved August 14, 2015.
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  66. ↑ "2015 BBVA Award". YouTube.
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  68. ↑ "2017 Redelsheimer Award".
  69. ↑ "2017 Fresenius Prize". "Fresenius" (PDF).
  70. ↑ "2017 Harvey Prize" (PDF).
  71. ↑ "2018 Leibinger karl-deisseroth".
  72. ↑ "2018 Eisenberg".
  73. ↑ "2018 Gairdner karl-deisseroth".
  74. ↑ "Kyoto Prize, Inamori Foundation". Kyoto Prize, Inamori Foundation. Retrieved March 13, 2019. "karl-deisseroth-wins-kyoto-prize-for-optogenetics.html". May 31, 2017.
  75. ↑ Hofschneider, Mark. "Light-sensitive microbial proteins and optogenetics". Lasker Foundation. Retrieved December 13, 2021.
  76. ↑ Louisa Gross Horwitz Prize 2022
  77. ↑ Japan Prize 2023
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