Epp Väli

Neural plasticity is the ability of nervous system to change its activity in response to stimuli by reorganizing its structure, functions, or connections and this is the main cellular basis for memory. Activity-regulated genes play crucial roles in the formation of neuronal plasticity, and dysregulation of this process gives rise to various nervous system disorders. The neurotrophin BDNF is among the best-studied activity-regulated genes, and its polymorphisms are associated with impairments in human cognition. Our results also place the basic helix-loop-helix transcription factor TCF4, that is implicated in a variety of psychiatric and autism spectrum disorders, to the group of activity-regulated transcription factors. The aim of this project is to study gene regulation in intellectual disability and autism spectrum disorders with emphasis on disease-associated transcription factors TCF4, SATB2, FOXP1, and neurotrophin BDNF for finding new drug targets.

The research infrastructure on experimental studies and applications of cellular processes aims at gathering national know-how in the field of cell and molecular biology, and aims at setting up an instrumental capability to develop competence and services in the fields of microbial and mammalian cell processes and their applications. The infrastructure will be built up jointly by the University of Tartu, Tallinn University of Technology, Tallinn University, Estonian University of Life Sciences and the Institute of Chemical Physics and Biophysics. The vision is to become a know-how and service centre to partner health, biotechnology and environment-focused public sector organisations, medical institutions, biotechnology and pharmacological companies. The focus will be on acquiring and setting up relevant instrumental complexes, development and offering of services, popularisation and dissemination of the field in order to ensure sustainability of researchers and future activities.

The nervous system consists of multiple cell types with distinct physiological specializations and gene expression patterns. In tissue, these cells form a complex, intertwined network that is subject to constant interaction between different cell types. This complexity poses a challenge for researchers in both separating cell types for analysis as well as studying interactions and information transfer between cells. In this application, we propose a molecular neuroscience study addressing both aspects. First, we are developing proteomics methods to allow analysis of newly synthesized proteins on a cell type-specific basis. Second, we shall use novel genetic tools for cell type-specific stimulation and gene expression analysis in primary co-cultures of neurons and astroglial cells. We shall use this system to probe gene expression signatures in neuron-astrocyte communication and determine the transmitters that form the basis of this communication.