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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6: Bio4Med - Cooperative involvement of 5-HT4 and 5-HT7 serotonin receptors and extracellular matrix modifiers in synaptic plasticity underlying the pathogenesis of depression

Supervisor:
prof. Jakub Wlodarczyk
Foreign partner:
Prof. Evgeni Ponimaskin; Hannover Medical School, Hannover, Germany
WWW
http://en.nencki.gov.pl/laboratory-of-cell-biophysics
Background:
The brain plasticity is a re-organization of the neuronal and synaptic networks that allows for changes in response to incoming environmental stimuli. One important component regulating synaptic function and plasticity is the extracellular matrix (ECM). Pathological forms of neuronal plasticity associated with profound atrophy of dendrites and spines underlie the multiple neuropsychiatric disorders including chronic stress, a major susceptibility factor for depression. Clinical observations on the efficacy of antidepressants targeting serotonergic system strongly suggest that serotonin and its receptors play a pivotal role in modulation of pathological plasticity. However, underlying molecular mechanisms, and in particular possible interplay between serotonergic system and ECM, remain poorly understood. The aim of this project is to define the relationship between serotonergic signaling, extracellular matrix and ECM proteases in modulating synaptic plasticity at the level of their downstream effectors with particular focus on small GTPases of Rho family. Methodology: Applied methods include quantitative molecular microscopy and biophysical methods, multidimensional and multiparametric quantitative image analysis, imaging of transparent brain (Clarity method), and FRET measurements. Also high-resolution immunogold and serial block-face scanning electron microscopy using 3View FE-SEM system will be applied. In addition, cloning and expression of recombinant proteins in different cell types and in organotypic cultures, siRNA techniques will be combined with electrophysiological and behavioral experiments.
Aim:
The aim of this project is to define the relationship between serotonergic signaling, extracellular matrix and ECM proteases in modulating synaptic plasticity at the level of their downstream effectors with particular focus on small GTPases of Rho family.
Requirements:
A scientific background in neuroscience and experience with at least one of the listed methods are required. Strong motivation to push aspects of this project forward is necessary. 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.