Chekulaeva lab

RNA metabolism in neurons and Neurodegeneration

Who are we?

We are a research lab aiming at understanding the molecular mechanisms underlying the subcellular localization and translation of RNA in neurons and neurodegeneration. Our lab is led by Marina Chekulaeva and is located in the center of Berlin at the Berlin Institute for Medical Systems Biology (BIMSB), a part of the Max Delbrück Center (MDC).

Research summary

Our lab is interested in the molecular mechanisms that regulate subcellular RNA localization, translation, and stability in neurons and neurodegeneration and the roles of RNA binding proteins (RBPs) and miRNAs in these processes. The neuron is a highly polarized cell consisting of the cell body (soma) and neurite extensions (axons and dendrites). Such polarity is crucial to neuronal function and relies largely on asymmetric subcellular translation and localization of RNAs and proteins. We combine systems biology, biochemical, and imaging methods to analyze subcellular RNA localization and translation.

Lay summary

Neurodegenerative disorders are devastating incurable diseases, predicted to become the second leading cause of death by 2040. A common theme across these disorders is the loss of neuron’s ‘branches’. One of the possible reasons behind this degeneration is the mislocalization of mRNAs. mRNAs are short genetic messages that give cells instructions on what types of proteins to make. A precise cellular ‘postal system’ is required to ensure the messages arrive in the right location. Some neurodegenerative diseases may develop because mRNAs do not reach these neuronal ‘branches’ or the wrong type of mRNA is delivered there. We want to understand why this happens. We focus on three specific areas. First, we want to identify what are the ‘postcodes’ in mRNAs that allow the cells to know where they must be delivered. Second, we want to identify the ‘postmen’, i.e., the molecules that ‘read’ the postcode, and ensure that the mRNA reaches the correct location. Finally, we look at samples from patients with ALS, a type of motor neuron disease, to identify the specific ‘postcodes’ and ‘postmen’ that may be malfunctioning in this disease.

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