Ed Boyden leads the Synthetic Neurobiology Group at the Massachusetts Institute of Technology (MIT), affiliated with both the MIT Media Lab and the McGovern Institute for Brain Research. His group focuses on developing innovative tools, creating technologies to understand the brain’s complex mechanisms and to address brain disorders.
Revolutionizing Brain Research with Light
One of the primary technologies pioneered by the Boyden lab is optogenetics, a method that allows scientists to control the activity of specific neurons using light. This approach involves genetically modifying neurons to express light-sensitive proteins called opsins. When exposed to particular frequencies of light, these opsins act as channels or pumps, altering the electrical potential across the neuron’s membrane and thereby activating or silencing its activity.
Optogenetics began with the 2004 discovery that channelrhodopsin-2 (ChR2), a protein from green algae, could be expressed in mammalian neurons and activated by blue light. This breakthrough, involving collaborations with Georg Nagel and Karl Deisseroth, demonstrated that neural activity could be controlled with millisecond precision. This enables researchers to precisely map neural circuits and investigate their functions.
The technology has been refined to include various opsins, allowing for activation or silencing with different colors of light, such as green, yellow, or red light. For example, halorhodopsin and archaerhodopsin can silence neurons by pumping chloride ions into or protons out of cells when exposed to green or yellow light. This versatility in light control enables scientists to study how different types of neurons contribute to complex brain functions.
The Boyden lab has played a significant role in distributing these optogenetic tools globally, fostering their widespread adoption in neuroscience, which has accelerated the study of neural circuits and their involvement in brain disorders. Continued systematic screening of genomes for new light-activated proteins and mutagenesis of existing opsins enhance optogenetic experiments, yielding more light-sensitive molecules with novel spectral characteristics.
Seeing the Unseen with Expansion Microscopy
Another technology developed by the Boyden lab is Expansion Microscopy (ExM), which addresses the challenge of visualizing biological structures at nanoscale resolution using conventional microscopes. Traditional light microscopy faces a physical limit, the diffraction limit, preventing observation of objects closer than approximately 300 nanometers. ExM overcomes this by physically enlarging the biological sample itself.
The process of ExM involves embedding fixed biological specimens, such as brain tissue, into a dense, swellable polymer hydrogel, often made of sodium polyacrylate. Key biomolecules within the sample, like proteins and nucleic acids, are chemically anchored to this polymer network. After anchoring and polymerization, the sample is mechanically homogenized, and then water is added.
The hydrogel then absorbs water and swells isotropically, expanding the embedded tissue typically around 4.5 times in linear dimension, or up to 10 times in advanced versions. This enlargement separates molecules and structures, allowing structures as small as 70 nanometers to become visible and distinct using widely available conventional fluorescence microscopes.
Expansion microscopy offers advantages including the preservation of molecular information within the expanded sample. The expanded specimens are optically clear, allowing for imaging of thicker samples. This technique aids in the detailed mapping of synapses, cells, and circuits across different species, including fruit flies, mice, non-human primates, and humans.
Impact Across Neuroscience and Beyond
The innovations from the Ed Boyden lab, particularly optogenetics and expansion microscopy, have advanced neuroscience research. These tools provide insights into how the brain functions, develops, and contributes to disease states. By enabling precise control of neural activity and ultra-high-resolution imaging of biological structures, they facilitate new discoveries.
The adoption of these technologies has led to a deeper understanding of neural circuits and their roles in various behaviors and cognitive processes. For instance, optogenetics has been used to investigate how specific cell types contribute to brain functions and disorders, leading to the causal assessment of neuronal roles within circuits. This has helped link cellular mechanisms to system-level phenomena.
The lab’s work also contributes to developing new diagnostic methods and therapeutic strategies for neurological and psychiatric disorders. The insights gained from these tools can inform treatment development. For example, optogenetics was used in mice models of Alzheimer’s disease to trigger specific brain waves, leading to a reduction in amyloid plaques, a finding now explored in human trials using non-optogenetic methods.
The interdisciplinary nature of the Boyden lab’s approach, combining neurobiology, chemistry, engineering, and computer science, has fostered a global community of researchers utilizing these tools. Their innovations advance fundamental biological understanding and are applied across diverse fields beyond neuroscience, including kidney disease, plant biology, and virology. This widespread use highlights their impact on biological analysis and repair.