A red thread in motor neuron disorders

Under a new grant from the EU, Marina Chekuleava of the MDC will lead a multinational consortium to find common mechanisms in diverse motor neuron diseases

Dr. Marina Chekulaeva. Credit: David Ausserhofer / MDC

Most of the things we enjoy – from things as simple as reading a text to the highly skilled motions of athletes – depend on motor neurons that connect the brain to skeletal muscles throughout the body. A at some point in our lives, about one in every 300 of us will experience a degeneration of these nerves, with consequences including progressive paralysis and severe disabilities. Marina Chekulaeva, head of a research lab at the Berlin Institute of Systems Biology (BIMBS) at the MDC, says that many forms of motor neuron disorders, or MNDs, stem from a common set of cellular defects. The EU has just awarded her a major grant to coordinate an international effort that will shed more light on these shared mechanisms.

“The pathogenic processes that lead to MNDs often arise from abnormalities in the way cells splice RNA molecules to create different proteins from the same gene, or transport them to their cellular destinations,” Chekulaeva says. “Other problems include stress on structures called the endoplasmic reticulum, which processes a huge number of proteins, and dysfunctions in energy-producing organelles called mitochondria.”

Embryonic stem cell-derived motor neurons. Credit: Samantha Mendonsa/BIMSB

Clarifying how these problems produce MNDs by disrupting networks of cellular processes will require diverse expertise. Drawing it together is a central goal of the EU’s Joint Program on Neurodegenerative Disease, the largest global research initiative devoted to these conditions. The grant will provide ~915.000 Euro for a period of 3 years to link Chekulaeva’s lab to important international partners. She will coordinate the project, combining her group’s work on RNA biology with computational expertise from the Weizmann Institute of Science in Israel, studies of neurodegenerative diseases using fly and mouse models at Radboud University in the Netherlands, and clinical research at the ALS Clinical Research Center in Italy.

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