Probing and engineering neuroplasticity
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.
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.
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.