Helena Tull

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.

Formation of new synapses, and alteration of the strength and stability of existing synapses are regarded as the main cellular basis for memory and long-term behavioral adaptations. Neuronal activity-regulated gene expression plays a crucial role in synaptic development and function, and its deregulation gives rise to various nervous system disorders. Knowledge about the regulatory mechanisms of activity-dependent gene expression is important both for understanding of nervous system function and for finding new drug targets. The aim of this project is to study the molecular mechanisms of neuronal activity-regulated gene expression, including transcription, translation and posttranslational modifications, in the nervous system health and disease. The studies are focused on two genes, the neurotrophin BDNF and the basic helix-loop-helix transcription factor TCF4.