Synthetic Neurobiology
Revealing insights into the human condition and repairing brain disorders via novel tools for mapping and fixing brain computations.
Our brains and nervous systems mediate everything we perceive, feel, decide, and do—and act as our ultimate interface to the world. An outstanding challenge for humanity is to understand these neuromedia interfaces at a level of abstraction that enables us to engineer their functions: repairing pathology, augmenting cognition, and revealing insights into the human condition. The Synthetic Neurobiology group invents and applies tools to analyze and engineer brain circuits in both humans and model systems. Our current neuroengineering focus is on devising technologies for controlling the processing within specific neural circuit targets in the brain. We hope that this synthetic neurobiology approach to the brain will help us better understand—and engineer improvements upon—the nature of human existence.

Research Projects

  • Cognitive Integration: The Nature of the Mind

    Joscha Bach and Adam Marblestone

    While we have learned much about human behavior and neurobiology, there is arguably no field that studies the mind itself. We want to overcome the fragmentation of the cognitive sciences. We aim to create models and concepts that bridge between methodologies, and can support theory-driven research. Among the most interesting questions: How do our minds construct the dynamic simulation environment that we subjectively inhabit, and how can this be realized in a neural substrate? How can neuronal representations be compositional? What determines the experiential qualities of cognitive processes? What makes us human?

  • Optogenetics and Synthetic Biology Tools

    Or Shemesh, Demian Park, Aimei Yang, Kate Adamala, Daniel Martin-Alarcon
    We have pioneered the development of fully genetically encoded reagents that, when targeted to specific cells, enable their physiology to be controlled via light, as well as other specific manipulations of cellular biological processes. Optogenetic tools enable temporally precise control of neural electrical activity, cellular signaling, and other high-speed physiological processes using light. Other tools we are developing enable the control and monitoring of protein translation and other key cell biological processes. Such tools are being explored throughout neuroscience and bioengineering, for the study and repair of brain circuits. Derived from the natural world, these tools highlight the power of ecological diversity, in yielding technologies for analyzing biological complexity and addressing human health. We distribute these tools as freely as possible.
  • Prototype Strategies for Treating Brain Disorders

    Nikita Pak, Christian Wentz, Yongxin Zhao, Joel Dapello, Nir Grossman

    New technologies for recording neural activity, controlling neural activity, or building brain circuits, may be capable some day of serving in therapeutic roles for improving the health of human patients: enabling the restoration of lost senses, the control of aberrant or pathological neural dynamics, and the augmentation of neural circuit computation, through prosthetic means. High throughput molecular and physiological analysis methods may also open up new diagnostic possibilities. We are assessing, often in collaborations with other groups, the translational possibilities opened up by our technologies, exploring the safety and efficacy of our technologies in multiple animal models, in order to discover potential applications of our tools to various clinically relevant scenarios. New kinds of "brain co-processor" may be possible which can work efficaciously with the brain to augment its computational abilities, e.g., in the context of cognitive, emotional, sensory, or motor disability.

  • Tools for Mapping the Molecular Structure of the Brain

    Shahar Alon, Shoh Asano, Jae-Byum Chang, Fei Chen, Amauche Emenari, Linyi Gao, Rui Gao, Dan Goodwin, Grace Huynh, Louis Kang, Manos Karagiannis, Adam Marblestone, Andrew Payne, Paul Reginato, Sam Rodriques, Deblina Sarkar, Paul Tillberg, Ru Wang, Oz Wassi

    Brain circuits are large, 3D structures. However, the building blocks -- proteins, signaling complexes, synapses--are organized with nanoscale precision. This presents a fundamental tension in neuroscience: to understand a neural circuit, you might need to map a large diversity of nanoscale building blocks, across an extended spatial expanse. We are developing a new suite of tools that enable mapping of the location and identity of the molecular building blocks of the brain, so that comprehensive taxonomies of cells, circuits, and computations might someday become possible, even in entire brains. One of the technologies we are developing enables large, 3D objects to be imaged with nanoscale precision, by physically expanding the sample -- a tool we call expansion microscopy (ExM). We are working to improve expansion microscopy further, and are developing, often in interdisciplinary collaborations, a suite of new labeling and analysis techniques to enable multiplexed readout.

  • Tools for Mapping the Molecular Structure of the Brain

    Daniel Oran, Pablo Valdes, Alex Wissner-Gross, Fei Chen, Linyi Gao, Sam Rodriques, Paul Tillberg, Asmamaw "Oz" Wassie, Shahar Alon, Jae-Byum Chang, Ru Wang, Yongxin Zhao, Manos Karagiannis, Adam Marblestone, Alexander Clifton, Jeremy Wohlwend, Andrew Payn

    Brain circuits are large, 3D structures. However, the building blocks–proteins, signaling complexes, synapses–are organized with nanoscale precision. This presents a fundamental tension in neuroscience: to understand a neural circuit, you might need to map a large diversity of nanoscale building blocks, across an extended spatial expanse. We are developing a new suite of tools that enable the mapping of the location and identity of the molecular building blocks of the brain, so that comprehensive taxonomies of cells, circuits, and computations might someday become possible, even in entire brains. One of the technologies we are developing enables large, 3D objects to be imaged with nanoscale precision, by physically expanding the sample–a tool we call expansion microscopy (ExM). We are working to improve expansion microscopy further, and are working, often in interdisciplinary collaborations, on a suite of new labeling and analysis techniques to enable multiplexed readout.

  • Tools for Recording High-Speed Brain Dynamics

    Jake Bernstein, Limor Freifeld, Ishan Gupta, Mike Henninger, Erica Jung, Changyang Linghu, Caroline Moore-Kochlacs, Kiryl Piatkevich, Nick Savidis, Jorg Scholvin, Guangyu Xu, Young Gyu Yoon, Kettner Griswold, Justin Kinney

    The brain is a three-dimensional, densely wired circuit that computes via large sets of widely distributed neurons interacting at fast timescales. Ideally it would be possible to observe the activity of many neurons with as great a degree of precision as possible, so as to understand the neural codes and dynamics that are produced by the circuits of the brain. Our lab and our collaborators are developing a number of innovations to enable such analyses. These tools will hopefully enable pictures of how neurons work together to implement brain computations, and how these computations go awry in brain disorders. Such neural observation strategies may also serve as detailed biomarkers of brain disorders or indicators of potential drug side effects. These technologies may, in conjunction with optogenetics, enable closed-loop neural control technologies, which can introduce information into the brain as a function of brain state ("brain co-processors").

  • Understanding Normal and Pathological Brain Computations

    Brian Allen, David Rolnick, Annabelle Singer, Harbi Sohal, Ho-Jun Suk, Giovanni Talei Franzesi, Yosuke (Bandy) Bando, Nick Barry

    We are providing our tools to the community, and also using them within our lab, to analyze how specific brain mechanisms (molecular, cellular, circuit-level) give rise to behaviors and pathological states. These studies may yield fundamental insights into how best to go about treating brain disorders.