Understanding and Engineering the Brain at the Molecular Scale
The brain is an intricate system where molecular interactions drive neural computation, plasticity, and disease progression. We aim to uncover the molecular principles underlying neural function and develop innovative bioengineering tools to study and manipulate neural activity. Our work spans fundamental biophysical mechanisms, synthetic biology, and translational neuroengineering, with a long-term goal of bridging basic neuroscience with therapeutic applications.
We take an interdisciplinary approach, integrating structural biology, protein engineering, synthetic biology, and neurobiology to study neural function and design novel tools for neuroscience and medicine.
Neurons rely on precise molecular interactions at the cell surface to transmit signals, process information, and adapt to their environment. We study how proteins, receptors, and ion channels contribute to neural function at the molecular level.
- Investigating biophysical and biochemical mechanisms of neural signal transduction.
- Mapping protein-protein interactions that regulate cell surface signaling.
- Developing new techniques from structural and mechanistic insights.
Related publications
Kim YS*#, Gillespie SM*, Geraghty AC, Yalçın B, Ivec AE, Yang A, Mancusi R, Hysinger J, Reed J, Drexler R, Quezada M, Malacon K, Woo P, Byun YG, Mount C, Lam M, Pan Y, Zuchero JB, Trotter J, Monje M#, “Neuroligin-3 interaction with CSPG4 regulates normal and malignant glial precursors through mechanotransduction”, biorxiv
Tajima S*, Kim YS*, Fukuda M, Jo YJ, Wang PY, Paggi JM, Inoue M, Byrne EFX, Kishi KE, Nakamura S, Ramakrishnan C, Takaramoto S, Nagata T, Konno M, Sugiura M, Katayama K, Matsui TE, Yamashita K, Kim S, Ikeda H, Kim J, Kandori H, Dror RO, Inoue K, Deisseroth K#, Kato HE#, Structural basis for ion selectivity in potassium-selective channelrhodopsins, Cell, 186, 1-20 (2023)
Kishi KE*, Kim YS*, Fukuda M*, Inoue M*, Kusakizako T*, Wang PY*, Ramakrishnan C, Byrne EFX, Thadhani E, Paggi JM, Matsui TE, Yamashita K, Nagata T, Konno M, Quirin S, Lo M, Benster T, Uemura T, Liu K, Shibata M, Nomura N, Iwata S, Nureki O, Dror RO, Inoue K, Deisseroth K#, Kato HE#, Structural basis for channel conduction in the pump-like channelrhodopsin ChRmine, Cell, 185, 1-18 (2022)
Kim YS*, Kato HE*#, Yamashita K, Ito S, Inoue K, Ramakrishnan C, Fenno LE, Evans KE, Paggi JM, Dror RO, Kandori H, Kobilka BK and Deisseroth K#, Crystal structure of the natural anion-conducting channelrhodopsin GtACR1, Nature 561 (7723), 343-348 (2018)
Kato HE*#, Kim YS*, Paggi JM, Evans KE, Allen WE, Richardson C, Inoue K, Ito S, Ramakrishnan C, Fenno LE, Yamashita K, Hilger D, Lee SY, Berndt A, Shen K, Kandori H, Dror RO, Kobilka BK and Deisseroth K#, Structural mechanisms of selectivity and gating in anion channelrhodopsins, Nature 561 (7723), 349-354 (2018)
By leveraging synthetic biology and protein engineering, we develop molecular tools to control and manipulate neural activity with high precision.
- Developing novel biointerfaces for studying neural function in vitro and in vivo.
- Enhancing expression systems in the brain for better delivery.
- Applying synthetic evolution and computational methods to optimize neural tools.
Related publications
Fenno LE*, Ramakrishnan C*, Kim YS*, Evans KE, Lo M, Vesuna S, Inoue M, Cheung KYM, Yuen E, Pichamoorthy N, Hong A and Deisseroth K, Comprehensive dual- and triple-feature intersectional single-vector delivery of diverse functional payloads to cells of behaving mammals, Neuron, 107, 1-18 (2020)
Liu J*, Kim YS*, Richardson C*, Tom A*, Ramakrishnan C, Birey F, Katsumata T, Chen S, Wang C, Wang X, Joubert L, Jiang Y, Wang H, Fenno LE, Tok JBH, Pasca SP, Bao Z# and Deisseroth K#, Genetically-targeted Chemical Assembly of Functional Materials in Living Cells, Tissues and Animals, Science 367 (6484) (2020)
Marshel JH*, Kim YS*, Machado TA*, Quirin S*, Benson B, Kadmon J, Raja C, Chibukhchyan A, Ramakrishnan C, Inoue M, Shane JC, McKnight DJ, Yoshizawa S, Kato HE, Ganguli S and Deisseroth K, Cortical Layer-specific Critical Dynamics Triggering Perception, Science 365 (6453) (2019)