Project Overview
The brain relies on precise control of gene expression to support learning, memory, and healthy communication between neurons. One important way cells achieve this control is through chemical marks added to RNA molecules, the messages that tell cells which proteins to make. These marks, known as RNA modifications, help determine how RNAs move, how stable they are, and how efficiently they produce proteins. Recent research has shown that these modifications are especially important in neurons and may play key roles in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS).
ALS is a devastating disorder in which the motor neurons gradually deteriorate and ultimately cause the patient’s death. Although many genetic factors have been linked to the disease, we still do not fully understand why these neurons are so vulnerable. A growing body of evidence suggests that disruptions in RNA regulation may contribute to early dysfunction at synapses, the communication points between neurons.
This project aims to uncover how RNA binding proteins operate specifically at synapses and how their functions change in ALS. To achieve this, we will build new molecular tools that allow us to map, with unprecedented precision, the proteins and RNA molecules that interact with key RNA-binding proteins in the brain. These tools use advanced technologies to “tag” nearby molecules inside living tissue, enabling their identification even within tiny synaptic structures. By revealing how RNA regulation breaks down at synapses in ALS, this research will uncover new early markers of disease, highlight pathways that could be targeted by future therapies, and establish powerful new tools that can be applied widely to the study of brain disorders.
Partners & Donors
Allan Kliger and friends
