Activity-Dependent Translational Profiling in Fragile X Neurons

FRAXA’s first-ever grant to researchers at the University of California at Berkeley goes to Dr. Nicholas Ingolia and Dr. J. Wren Kim to analyze the proteomics of Fragile X neurons using a newly developed tool which can distinguish the profiles of neurons that are actively responding to signals.

Drs. Ingolia, Wren Kim, at University of California at Berkeley
$90,000 Grant

Nicholas Ingolia, PhD
Principal Investigator

J. Wren Kim, PhD
FRAXA Postdoctoral Fellow

University of California at Berkeley
2017-2018 FRAXA Research Grant
$90,000 over 2 Years

by J. Wren Kim, PhD

In our brains, neurons function by sending and receiving electrical and chemical signals. This signaling process forms the molecular foundation of any brain function; even the most complicated brain activity, such as consciousness, relies on this signal transmission. When two neurons communicate to each other, this causes changes within each of them that alter their connection strength — we think that these changes enable us to learn and to memorize. Changes in connective strength require production of new proteins, which are the primary building blocks for a cell. Form follows function; just like building a complex architecture, making the precise kinds and numbers of neuronal components are absolutely critical for these processes.

Previous studies have examined the proteome (levels of proteins in a cell) and the transcriptome (blueprints for the protein production) of Fragile X, but without taking account of the dynamic nature of protein production coupled to signal reception. However, we realized that these dynamics indeed might be key to understanding the Fragile X brain because Fragile X neurons seem to respond differently to signals. Understanding these differences, and the time course of this response, can help us to identify new treatment targets for Fragile X.

We are developing a new molecular tool to identify the set of proteins being made in neurons. Unlike existing methods, our tool can distinguish the profiles of neurons that are actively responding to signals. Therefore, this tool enables us to study the behavior of Fragile X neurons which are involved in active communication. We will study the alterations in activity-dependent protein synthesis in Fragile X neurons under a number of different conditions, and in response to different kinds of neurotransmitters. We believe that a better understanding of how a Fragile X brain responds to signals could ultimately expand therapeutic options by providing novel strategies to adjust for the differences in the Fragile X brain.

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