Our research group is interested in the molecular mechanisms influencing experience-driven activation and equilibration of neuronal circuits in the mouse brain.
We are currently studying the spatiotemporal dynamics of a set of proteins that transmit the signal from synapses to the nucleus by using a broad spectrum of techniques including protein engineering, imaging, biochemistry, electrophysiology, genomics, transcriptomics, and proteomics.
By focusing on experience-driven neuronal circuit responses at the molecular level, we aim to develop new therapeutic approaches for neurodevelopmental disorders such as autism spectrum disorders. We are located at the Molecular Neurobiology Division at Karolinska Institute, composed of outstanding scientists applying interdisciplinary approaches to cutting edge problems in a collaborative and stimulating environment.
Project 1. Probing and programming protein signaling circuits within neuronal circuits
Neuronal activity dependent molecular signaling processes are central for brain development and plasticity. These molecular events form the mechanistic basis of complex neural computation, learning and memory. Experience-driven activation of proteins often at the post-translational level mediate the rapid events including synaptic modifications, metabolic adaptations, and the transfer of the cytosolic protein signals into the nucleus to influence gene expression.
The Dagliyan laboratory focuses on specific molecular events happening at these different time scales, starting from the immediate modifications at the synapse, such as actin-modifying protein signaling, to longer time scale molecular events such as protein modifications that mediate transcription initiation, elongation, and RNA splicing, which are key processes for the behaviorally induced plasticity of neuronal circuits.
Project 2. Development of molecular technologies to visualize and control protein activity in neuronal circuits
Protein signaling in cells is precisely coordinated in space and time. Like many other cell types, individual neurons within neuronal circuits use genetically encoded molecular networks to make complex decisions. The Dagliyan Lab is interested in the molecular logic and design principles governing the function of protein networks in neuronal circuits. To this end, we are building new molecular technologies that enable spatiotemporal dynamics of proteins that are inaccessible by other means.
We have previously engineered protein switches and sensors to reveal signaling dynamics of individual single cells. These sensors sense the conformational changes of proteins and thereby their activity states, whereas the protein switches we have created have enabled the control of conformation by engineered drug- or light-gated small domains inserted at allosteric sites of the target protein. We now use these tools, as well as the new types of tools we are currently generating, in neurons to deconstruct and reconstruct the protein networks within neuronal circuits.
Yu (Ivy) ZhangPhD student
Yu (Ivy) Zhang, M.S. student
- Swedish Research Council
- Karolinska Institutet Allocation Grant
Dagliyan and Whitwam,..,Greenberg, 2022. In preparation
Engineering extrinsic disorder to control protein activity in living cells.
Dagliyan O, Tarnawski M, Chu PH, Shirvanyants D, Schlichting I, Dokholyan NV, Hahn KM
Science 2016 12;354(6318):1441-1444
Rational design of a ligand-controlled protein conformational switch.
Dagliyan O, Shirvanyants D, Karginov AV, Ding F, Fee L, Chandrasekaran SN, Freisinger CM, Smolen GA, Huttenlocher A, Hahn KM, Dokholyan NV
Proc Natl Acad Sci U S A 2013 Apr;110(17):6800-4
Computational design of chemogenetic and optogenetic split proteins.
Dagliyan O, Krokhotin A, Ozkan-Dagliyan I, Deiters A, Der CJ, Hahn KM, Dokholyan NV
Nat Commun 2018 10;9(1):4042
Engineering proteins for allosteric control by light or ligands.
Dagliyan O, Dokholyan NV, Hahn KM
Nat Protoc 2019 06;14(6):1863-1883
Controlling protein conformation with light.
Dagliyan O, Hahn KM
Curr Opin Struct Biol 2019 08;57():17-22
Engineering a switchable single-chain TEV protease to control protein maturation in living neurons.
Renna P, Ripoli C, Dagliyan O, Pastore F, Rinaudo M, Re A, Paciello F, Grassi C
Bioeng Transl Med 2022 May;7(2):e10292
Bidirectional perisomatic inhibitory plasticity of a Fos neuronal network.
Yap EL, Pettit NL, Davis CP, Nagy MA, Harmin DA, Golden E, Dagliyan O, Lin C, Rudolph S, Sharma N, Griffith EC, Harvey CD, Greenberg ME
Nature 2021 02;590(7844):115-121
Biosensors based on peptide exposure show single molecule conformations in live cells.
Liu B, Stone OJ, Pablo M, Herron JC, Nogueira AT, Dagliyan O, Grimm JB, Lavis LD, Elston TC, Hahn KM
Cell 2021 10;184(22):5670-5685.e23
Rational design and implementation of a chemically inducible heterotrimerization system.
Wu HD, Kikuchi M, Dagliyan O, Aragaki AK, Nakamura H, Dokholyan NV, Umehara T, Inoue T
Nat Methods 2020 09;17(9):928-936