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Roles of RNA-binding proteins in subcellular RNA localization and translation in neurons


Project Description

The subcellular localization and translation of mRNAs are fundamental biological processes. They underlie establishment of body axis, cell growth, cell migration, and synaptic plasticity, which serves as a foundations of learning and memory. Many neurological disorders are associated with a failure to localize and translate mRNAs at specific subcellular sites. Our prior work has identified a number of RBPs and miRNAs with potential regulatory roles in mRNA localization and local translation in neurons (Zappulo et al., 2017). The aim of the project will be to identify the mRNA targets of these RBPs and dissect the underlying mechanisms of function. The project will involve a combination of biochemical (RNA-seq, Ribosome profiling, polysome profiling, PAR-CLIP, RNA-IP, Crispr/CAS-mediated knockouts and tagging, reporter assays), computational and imaging approaches in cultured cells (mESC and hiPSC differentiation systems) and primary neurons.

The Max Delbrück Center for Molecular Medicine (MDC) is one of the leading biomedical institutes dedicated to interdisciplinary research. The most recent expansion of the MDC is the Berlin Institute for Medical Systems Biology (BIMSB). BIMSB is a multidisciplinary environment with half computational and half wet biology labs, running an extensive scientific program in systems biology, integrating high-throughput technologies with bioinformatics, biochemistry, molecular and developmental biology. For more information on the institute and the lab: http://www.chekulaevalab.org; http://www.mdc-berlin.de/bimsb

Funding Notes

Ideal candidate should have Master degree in biochemistry, molecular or computational biology, interest in RNA biology and mechanisms of gene regulation, and good knowledge of English. Wet-lab candidates should have experience in basic molecular biology techniques and cell culture. Computational candidates should have programming skills for data analysis preferably in R and in one of the scripting languages such as Perl/Python. To apply, please send your motivation letter and CV with contact details of two referees to marina.chekulaeva(at)mdc-berlin.de

References

1. Zappulo A, van den Bruck D, Ciolli Mattioli C, Franke V, Imami K, McShane E, Moreno-Estelles M, Calviello L, Filipchyk A, Peguero-Sanchez E, Müller T, Wohler A, Birchmeier C, Merino E, Rajewsky N, Ohler U, Mazzoni E, Selbach M, Akalin A, and Chekulaeva M. RNA localization is the key determinant of neurite-enriched proteome. (2017). Nature Communications, https://www.nature.com/articles/s41467-017-00690-6
2. Chekulaeva, M, Landthaler, M. (2016). Eyes on translation. Mol. Cell 63(6):918-25, http://dx.doi.org/10.1016/j.molcel.2017.02.021

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