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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20: Bio4Med - Relationship between nuclear actin dynamics and chromatin organisation

dr Tytus Bernas
Foreign partner:
Dr Erik Manders, Swammerdam Institute for Life Sciences, University of Amsterdam, The Netherlands
Actin plays a major role in cell nuclei, participating in: RNA synthesis, DNA replication, chromatin remodeling and long-range movement of chromosomal loci. Similarly to cytoplasm, this compartment contains a number of proteins (cofilin, profilin, CapG and gelsolin) which influence formation of filamentous actin. Conversely, induced actin depolymerization leads to major changes of nuclear chromatin distribution. However, despite wealth of indirect evidence, the reports of actin filaments under physiological conditions are scarce. It is postulated that these nuclear actin filaments are dynamic structures of sub-micron size. Polymerization decreases transiently velocity of actin movement, depending on the size of the protein aggregates. Concentration of nuclear actin is sufficient to induce its polymerization, depending on local interaction with factors which modulate actin nucleation. Moreover, this process is affected by movement of the protein between nucleus and cytoplasm. Thus, depending on the region of nucleus fractions of polymeric (immobile), oligomeric and monomeric (mobile) forms of actin may differ. Actin polymerization correlates with local chromatin architecture and participates in movement of large chromatin blocks.
We will investigate the dynamics of polymeric actin in cell nucleus and its relationship to chromatin distribution, by providing the answers to the following detailed research questions: 1. What is the spatial distribution and organization of the putative nuclear actin filaments? 2. Is the actin dynamics of actin correlated with nuclear architecture? 3. Does local actin concentration affect its polymerization in the nucleus? 4. Is actin polymerization modulated by interaction with other proteins? 5. Does actin participate in rearrangement of chromatin in the nucleus? We will use a range of fluorescence and electron microscopy techniques to visualize cell nuclei and image processing to quantify dynamics of actin and chromatin.
Ideal candidate should have some experience in biological light microscopy and image processing. Programing skills, familiarity with electron microscopy and molecular biology techniques will be an advantage. Motivation to carry out scientific research, attention to details and organisational skills are required. Fluency in English is essential. 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.