Copper is an essential cofactor for more than twenty enzymes crucial for cellular energy production, antioxidative defense, and oxidative metabolism. Free copper ions, however, are toxic and copper metabolism is therefore highly controlled. Dysregulation of copper homeostasis occurs in multiple diseases, including Wilson's (WD) and Alzheimer's disease (AD). This project strives to develop a comprehensive understanding of human copper metabolism and tools for its regulation. This will be achieved using a systems biology approach, which we applied earlier to intracellular Cu(I) proteome. We will expand this research to Cu(II) proteome in the blood and cerebrospinal fluid by using a novel LC-ICP MS-based approach. The expected results will substantially advance the knowledge on copper metabolism, and facilitate the search for molecular tools for its regulation. The latter will be tested in cellular and animal disease models and could provide novel molecular tools for WD and AD treatment.
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.
The aim of the centre is to translate the rapid progress in the field of genomics and other “-omics” technologies into improved understanding of molecular and evolutionary mechanisms of disease as well as improved prevention, diagnosis and clinical care. The Centre integrates 12 research units from University of Tartu, Estonian Biocentre and Tallinn University of Technology.