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RNA biology in neurons and neurodegeneration


   Medical Systems Biology

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  Dr Marina Chekulaeva  Applications accepted all year round  Funded PhD Project (Students Worldwide)

About the Project

For cells to perform their biological functions, they need to able to adopt specific shapes and form functionally distinct subcellular compartments. This is achieved via the asymmetric localisation of RNAs and proteins within a cell. This process underlies the establishment of body axis, cell growth and migration, learning and memory. In neurons, defects in mRNA localisation may lead to degeneration of neuronal extension – axons.

The successful candidate will work with ALS patient-derived hiPSCs and hiPSC-derived motor neurons to investigate how changes in RNA metabolism contribute to the mechanism of neurodegeneration. The project will rely on a combination of biochemical, omics (Ribo-seq, CLIP-seq), computational, CRISPR/Cas-mediated gene editing, and imaging approaches, including a compartmentalized neuronal culture that allows the separation of subcellular compartments in combination omics analyses (Zappulo et al. 2017; Ludwik et al. 2019; Ciolli et al. 2020). The project will involve collaboration with international partners, contributing different expertise to the project, including computational analysis and clinical research.

Ideal candidate should have Master's degree in biology, biochemistry, or molecular biology, experience in molecular biology techniques and cell culture, interest in RNA biology and mechanisms of gene regulation, and speak fluent English. Experience in hiPSC work and RNA biology techniques are an advantage. To apply, please send your motivation letter and CV with contact details of at least two referees, as a single pdf file, to marina.chekulaeva(at)mdc-berlin.de


References

1. von Kuegelgen N*, Mendonsa S*, Dantsuji S*, Ron M*, Kirchner M, Zerna N, Bujanic L, Mertins P, Ulitsky I# and Chekulaeva M# (2021). Massively parallel identification of zipcodes in primary cortical neurons. BioRxiv, dhttp://dx.doi.org/10.1101/2021.10.21.465275
2. Zappulo, A.*, van den Bruck, D.*, Ciolli Mattioli, C.*, Franke, V.*, Imami, K., McShane, E., Moreno-Estelles, M., Calviello, L., Filiipchyk, A., Peguero-Sanchez, E., Mueller, T., Woehler, A., Birchmeier, C., Merino, E., Rajewsky, N., Ohler. U., Mazzoni, E., Selbach, M., Akalin, A., and Chekulaeva, M. (2017). RNA localization is a key determinant of neurite-enriched proteome. Nature Communications, http://dx.doi.org/10.1038/s41467-017-00690-6
3. Ciolli Mattioli C., Rom A., Franke V., Imami K., Arrey G., Terne M., Woehler A., Akalin A., Ulitsky I., and Chekulaeva M. (2018). Alternative 3′ UTRs direct localization of functionally diverse protein isoforms in neuronal compartments (2020). Nucleic Acids Research, https://doi.org/10.1093/nar/gky1270
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