Ribosome function in plasticity and neurodevelopmental disorders

A single faulty gene can derail the brain's protein-making machinery, locking neurons into a state of abnormal communication that underlies Fragile X Syndrome—the most common inherited cause of autism and intellectual disability. This research tackles a fundamental gap: we know that neurons in Fragile X make too much protein, but we do not know which specific messenger RNAs are being over-translated, nor how that excess protein production physically disrupts the connections between brain cells. The researcher will test whether reducing the number of ribosomes—the cell's protein factories—can correct the neurological symptoms in a mouse model of Fragile X. They will also map which mRNAs are translated when synapses strengthen versus weaken, using a technique that pulls ribosomes directly off active messenger RNAs. If successful, this work would reveal the molecular wiring diagram that links excessive protein synthesis to synaptic dysfunction in Fragile X. That could point toward new therapeutic targets—perhaps drugs that dial back ribosome production rather than trying to fix each downstream symptom. More broadly, it would explain how the brain normally chooses which proteins to make when it needs to strengthen or weaken a connection, a fundamental question in neuroscience with implications for any disorder involving faulty synaptic plasticity.