This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie COFUND grant agreement No 665735.

Bio4Med Research Projects:


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5: Bio4Med - Architectural remodeling of the neuronal cell nucleus in Rett syndrome

Supervisor:
prof. Grzegorz Wilczynski
Foreign partner:
Dr Angel Barco, Instituto de Neurociencias de Alicante, Alicante, Spain
WWW
http://www.nencki.gov.pl/en/laboratory-of-molecular-and-systemic-neuromorphology http://in.umh.es/barcolab/who.html
Background:
Structural changes in the neuronal cell nucleus have recently emerged as a higher-order epigenetic mechanism that can have a profound influence on gene expression in the brain. We found that induction of extensive architectural remodeling of heterochromatin by transgenic expression of histone 2B-GFP fusion protein in neurons, resulted in transcriptional silencing of a distinctive set of genes involved in neurotransmission, and lead to cognitive decline and autistic-like behavioral abnormalities (Ito, Magalska et al., in press). Such a phenotype bears some similarities to the symptoms found in patients suffering from the Rett syndrome, a disorder resulting from mutations in the chromatin regulator MeCP2 protein. Therefore, in this project, we want to examine, whether disturbances of neuronal nuclear architecture can underlie the pathogenesis of Rett syndrome. Data analysis from morphological studies: to analyze spatial positioning of the genes within neuronal nuclei we will use high-throughput innovative milticolor three-dimensional fluorescence in situ hybridization (3D FISH) with confocal microscopic detection. Data analysis from ChIPseq or Circular Chromosome conformation capture (4C) or Carbon-Copy Chromosome Conformation Capture (5C): to obtain information on chromatin states, RNA polymerase II occupancy and lamina interaction, and to analyze the threedimensional organization of chromosomes in its natural state.
Aim:
To examine higher-order architecture of neuronal chromatin in a) rodent models of epilepsy, major depression, Rett syndrome, schizophrenia, Huntington disease and Alzheimer disease, and b) human brain samples obtained during epilepsy surgery, and samples collected during autopsies from patients affected by relevant neuropsychiatric disorders.
Requirements:
Outstanding expertise in computational methods of data analysis for molecular biology techniques; deep interest in quantitative analysis of microscopy imaging data. Candidates must not have resided or carried out their main activity (work, studies, etc.) in Poland for more than 12 months in the past 3 years.