Edward Boyden

Last updated
Edward Boyden
Ed Boyden MIT.jpg
Boyden at the MIT McGovern Institute
Born (1979-08-18) August 18, 1979 (age 45)
Alma mater
Awards Perl-UNC Prize (2011)
IET A F Harvey Prize (2011)
The Brain Prize (2013)
Breakthrough Prize in Life Sciences (2016)
Gairdner Foundation International Award (2018)
Rumford Prize (2019)
National Academy of Sciences (2019)
Warren Alpert Foundation Prize (2019)
Wilhelm Exner Medal (2020)
Scientific career
Institutions
Thesis Task-specific neural mechanisms of memory encoding  (2005)
Doctoral advisor
Notable students

Edward S. Boyden is an American neuroscientist and entrepreneur at MIT. He is the Y. Eva Tan Professor in Neurotechnology, and a full member of the McGovern Institute for Brain Research. [1] He is recognized for his work on optogenetics and expansion microscopy. Boyden joined the MIT faculty in 2007, and continues to develop new optogenetic tools as well as other technologies for the manipulation and analysis of brain structure and activity. [2] He received the 2015 Breakthrough Prize in Life Sciences. [3]

Contents

Early life and education

Boyden was born in Plano, Texas. His mother has a masters in biochemistry and conducted nicotine research, staying home to tend to Boyden and his sister. His father was a management consultant. In childhood wanted to understand humanity, at first preferring math over science. He eventually pivoted to being interested in how our minds are capable of understanding math. As a young teenager, his thoughts resulted in what he now calls the "loop of understanding": Math is how we understand things at a deep level, our minds do math, the brain gives rise to our minds, biology governs our brains, chemistry implements biology, the principles of physics rule over chemistry, and physics run on math. It’s a loop from math to math, with all the knowledge in between. [4]

Boyden won a statewide science fair in Texas at age 12 with a project in geometry. [4] At 14, Boyden attended the Texas Academy of Mathematics and Science at the University of North Texas where he studied chemistry and mathematics alongside his high school coursework. There, he worked in Paul Braterman's lab examining the origins of life chemistry. [5]

Boyden began his studies at MIT in 1995 at 16, skipping two grades. [4] He earned a M.Eng. in electrical engineering and computer science in addition to two B.S. in electrical engineering and computer science and physics, graduating at age 19. Boyden worked in Neil Gershenfeld's group in quantum computing.

In 1999, Boyden began a PhD in neurosciences at Stanford University under the supervision of Jennifer Raymond and Richard Tsien. He completed it in 2005. [5]

Career

Following his PhD, Boyden worked as a Helen Hay Whitney postdoctoral fellow in the departments of bioengineering, applied physics, and biology at Stanford University for a year. There, he worked with Mark Schnitzer and Karl Deisseroth to invent optical methods in neuroscience research. [5] In 2006, he moved to MIT to work as a visiting scientist in the MIT Media Lab, leading the Neuroengineering and Neuromedia Group. [5]

In 2007, Boyden established the Synthetic Neurobiology Group at MIT and also began working as an assistant professor in the MIT Media Lab and MIT Department of Biological Engineering. The next year, he became an assistant professor in the MIT Department of Brain and Cognitive Sciences. [5]

Boyden became an investigator at the MIT McGovern Institute in 2010. [5] In 2013, he established the MIT Center for Neurobiological Engineering, which he now co-directs alongside Alan Jasanoff. [6] He became an extramural member of the MIT Koch Institute for Integrative Cancer Research in 2017 before he was appointed the Y. Eva Tan Professor in Neurotechnology at MIT a year later. [5] 7 years after arriving at MIT, Boyden was awarded tenure as a full time professor. [7]

In 2020, Boyden became an investigator at the Howard Hughes Medical Institute. The following year, he began co-directing the K. Lisa Yang Center for Bionics at MIT. [5]

Research

Boyden's research encompasses optogenetics, expansion microscopy, deep brain stimulation, multiplexed imaging, machine learning, and more.

Optogenetics

In optogenetics, a light-sensitive ion channel or pump 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, [8] 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. [9]

Boyden reported in 2007 that targeting the codon-optimized light-driven halorhodopsin chloride pump (Halo) from Natronomas pharaonis allowed for optogenetic silencing with yellow light. [10] Later in 2010, he reported that archaerhodopsin-3 (Arch) from Halorubrum sodomense facilitated near-complete silencing of neurons using yellow light. Arch is also capable of spontaneously recovering from inactivation unlike Halo, which goes into lengthy inactive states. Its high performance enabled many new neuroscientific investigations using brain engineering. [11]

In 2014, Boyden reported how the channelrhodopsin Chronos could respond extremely fast to light, and how the channelrhodopsin Chrimson responded to red light. Chronos's kinetics is quicker than previous channelrhodopsins but is more sensitive to light. This discovery enabled two-color activation of neurons without significant cross-talk. [12] This led to the first optogenetics in people in 2021, where a blind patient was injected with an adeno-associated viral vector encoding ChrimsonR coupled with goggle-enabled light stimulation. The patient successfully perceived, located, counted, and touched objects using the vector-treated eye with the goggles. This case reports the greatest partial functional recovery to date, for such forms of blindness. [13]

The cruxhalorhodopsin (Jaws) from Haloarcula salinarum was engineered to induce inhibition in response to red light in 2014. [14] In 2017, Boyden designed a high-efficacy soma-targeted opsin through combining the N-terminal 150 residues of kainate receptor subunit 2 (KA2) to the high-photocurrent channelrhodopsin CoChR. This restricts its expression to neural somas, responding to holographic stimulation with temporal precision. [15]

Expansion microscopy

Expansion microscopy (ExM) was developed as an alternative to the light microscope, which is limited in resolution. In 2015, Boyden was able to expand a specimen by synthesizing a swellable polymer network within it. By attaching specific label on the network, its swelling allows for the isotropic separation and optical resolution. This allows for superresolution microscopy using diffraction-limited microscopes. [16] ExM has been optimized for proteins, [17] nucleic acids, [18] clinical tissues, [19] decrowding, [20] in situ sequencing, [21] and has developed a larger expansion factor. [22] In 2018, Boyden developed a method of shrinking 3D printed materials to achieve nanoscale feature sizes. By using hydrogel scaffolds, Implosion Fabrication (ImpFab) creates conductive 3D silver nanostructures with complex geometries and resolutions in the tens of nanometers. [23]

Deep brain stimulation

In 2017, Boyden reported a noninvasive method of deep electrical stimulation of neurons. By delivering electric fields at frequencies higher than that able to recruit neural firing but within its dynamic range, neurons within a region enveloped by the electric field can be modulated. This temporal interference (TI) successfully altered motor patterns in living mice. [24] TI was validated in humans in 2023 where it modulated hippocampal activity and increased the accuracy of episodic memories in healthy subjects. [25]

Multiplexed imaging

Multiplexed imaging is the simultaneous measurement of the dynamics of many signals within a signal transduction network. In 2020, Boyden fused a fluorescent reporter to a pair of a self-assembling peptides to create signaling reporter islands (SiRIs), which can be modularly designed. SiRIs can thus be adapted for simultaneous measurement of multiple signals in a network within single cells distant enough to be resolved under a microscope but close enough to spatially sample the biology (spatial multiplexing). [26] Temporally multiplexed imaging (TMI), reported in 2023, uses genetically encoded fluorescent proteins with temporal properties to represent different signals. This is used to examine relationships between kinase activities within single cells in addition to cell-cycle activities. [27] In 2018, Boyden reported a novel method of engineering complex proteins toward multidimensional specification through robotically picking identified cells as expressing proteins simultaneously exhibiting several properties. This enables the screening of hundreds of thousands of proteins in a few hours while evaluating each for multiple performance properties. [28] The robot was applied to develop a fluorescent voltage indicator, Archon. Voltage imaging, using Archon as well as indicators made by other groups, was applied in areas of the mouse brain in 2019 [29] and later across the entire brains of larval zebrafish in 2023. [30]

Entrepreneurship

Boyden has nearly 300 patented inventions, including a steerable surgical stapler, methods and apparatus for neuromodulation, expansion microscopy, and light-activated proton pumps. [31]

Boyden is the co-founder of Elemind, [32] a neurotechnology company that augments sleep, attention, and the human experience. [33] Elemind launched its neurotech headband that employs brainwaves to treat sleep disorders, long-term pain, and tremors on June 4, 2024. [34]

He also co-founded Cognito Therapeutics, a company developing therapeutics designed to improve the lives of patients living with neurodegenerative disease. Specifically, Boyden aims utilize findings about sensory stimulation evoking gamma activity in Alzheimer's disease to slow its progression. [35]

Boyden co-founded Expansion Technologies, aiming to enable the early disease detection by utilizing their novel super-resolution imaging method that physically expands samples, [36] as well as Synlife, which innovates therapeutic platforms through bottom-up engineering of synthetic cells with a focus on the encapsulation of enzyme pathways. [37]

Boyden is the scientific advisor of E11 Bio, a nonprofit project focused on neurotechnology development with a focus on brain circuit mapping. [38]

He is the head of advisory board at Inner Cosmos whose mission is to heal depression with their Digital Pill, a penny-sized implant rebalancing brain networks with microstimulations. [39]

Personal life

At Stanford, Boyden met Xue Han, now a neuroscientist at Boston University. They are raising two children together. [4]

Honors and awards

Related Research Articles

Behavioral neuroscience, also known as biological psychology, biopsychology, or psychobiology, is part of the broad, interdisciplinary field of neuroscience, with its primary focus being on the biological and neural substrates underlying human experiences and behaviors, as in our psychology. Derived from an earlier field known as physiological psychology, behavioral neuroscience applies the principles of biology to study the physiological, genetic, and developmental mechanisms of behavior in humans and other animals. Behavioral neuroscientists examine the biological bases of behavior through research that involves neuroanatomical substrates, environmental and genetic factors, effects of lesions and electrical stimulation, developmental processes, recording electrical activity, neurotransmitters, hormonal influences, chemical components, and the effects of drugs. Important topics of consideration for neuroscientific research in behavior include learning and memory, sensory processes, motivation and emotion, as well as genetic and molecular substrates concerning the biological bases of behavior. Subdivisions of behavioral neuroscience include the field of cognitive neuroscience, which emphasizes the biological processes underlying human cognition. Behavioral and cognitive neuroscience are both concerned with the neuronal and biological bases of psychology, with a particular emphasis on either cognition or behavior depending on the field.

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 578 nm. Halorhodopsin also shares sequence similarity to channelrhodopsin, a light-gated ion channel.

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 Miesenböckef> 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">Karl Deisseroth</span> American optogeneticist (born 1971)

Karl Alexander Deisseroth is an American scientist. He is the D.H. Chen Foundation Professor of Bioengineering and of psychiatry and behavioral sciences at Stanford University.

<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.

Expansion microscopy (ExM) is a sample preparation tool for biological samples that allows investigators to identify small structures by expanding them using a polymer system. The premise is to introduce a polymer network into cellular or tissue samples, and then physically expand that polymer network using chemical reactions to increase the size of the biological structures. Among other benefits, ExM allows those small structures to be imaged with a wider range of microscopy techniques. It was first proposed in a 2015 article by Fei Chen, Paul W. Tillberg, and Edward Boyden. Current research allows for the expansion of samples up to 16x larger than their initial size. This technique has been found useful in various laboratory settings, such as analyzing biological molecules. ExM allows researchers to use standard equipment in identifying small structures, but requires following of procedures in order to ensure clear results.

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">Doris Tsao</span> American neuroscientist

Doris Ying Tsao is an American neuroscientist and professor of neurobiology and molecular cell biology at the University of California, Berkeley. She was formerly on the faculty at the California Institute of Technology for 12 years. She is recognized for pioneering the use of fMRI with single-unit electrophysiological recordings and for discovering the macaque face patch system for face perception. She is a Howard Hughes Medical Institute Investigator and the director of the T&C Chen Center for Systems Neuroscience. She won a MacArthur "Genius" fellowship in 2018. Tsao was elected a member of the National Academy of Sciences in 2020. In 2024 she was awarded a Kavli Prize in neuroscience along with Nancy Kanwisher and Winrich Freiwald for the discovery and study of specific areas in the brain that perform facial recognition. Also in 2024 she received the Rosenstiel Award. After joining UC Berkeley in 2021, her current research explores visual perception in primates in order to understand how the brain creates our sense of reality.

Zhuo-Hua Pan is a Chinese-American neuroscientist, known for his foundational contributions to optogenetics. He is the Edward T. and Ellen K. Dryer Endowed Professor of Ophthalmology at Wayne State University, and Scientific Director of the Ligon Research Center of Vision at the university's Kresge Eye Institute.

<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.

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.

Jessica Cardin is an American neuroscientist who is an associate professor of neuroscience at Yale University School of Medicine. Cardin's lab studies local circuits within the primary visual cortex to understand how cellular and synaptic interactions flexibly adapt to different behavioral states and contexts to give rise to visual perceptions and drive motivated behaviors. Cardin's lab applies their knowledge of adaptive cortical circuit regulation to probe how circuit dysfunction manifests in disease models.

Fiber photometry is a calcium imaging technique that captures 'bulk' or population-level calcium (Ca2+) activity from specific cell-types within a brain region or functional network in order to study neural circuits Population-level calcium activity can be correlated with behavioral tasks, such as spatial learning, memory recall and goal-directed behaviors. The technique involves the surgical implantation of fiber optics into the brains of living animals. The benefits to researchers are that optical fibers are simpler to implant, less invasive and less expensive than other calcium methods, and there is less weight and stress on the animal, as compared to miniscopes. It also allows for imaging of multiple interacting brain regions and integration with other neuroscience techniques. The limitations of fiber photometry are low cellular and spatial resolution, and the fact that animals must be securely tethered to a rigid fiber bundle, which may impact the naturalistic behavior of smaller mammals such as mice.

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