NIH awards $6.8 million for stem cell neural-development project

CAMBRIDGE, Mass. — The National Institutes of Health has awarded a team of researchers from Whitehead Institute, MIT and Columbia University $6.8 million for analyzing the process by which embryonic stem cells develop into neurons. Understanding of the earliest stages of neural development may lead to more effective methods of treating a host of neurodegenerative diseases for which current therapies are limited.

“Our goal is to take the entire neurogenesis process apart so that we can understand the key molecular components,” says MIT computational biologist David Gifford, who is also an Affiliate Member of Whitehead Institute.

In addition to Gifford, lead investigator on the project, participants include Rudolf Jaenisch and Richard Young from Whitehead Institute; and Thomas Jessell, Hynek Wichterle, Christopher Henderson and Umrao Monani from Columbia University. While Whitehead scientists are experts in stem cell biology and in high-throughput methods for capturing genomic data, the Columbia team specializes in neural development. Gifford’s lab will create the computational tools for analyzing the data.

This five-year project will be divided in three components. First, Columbia researchers will identify groups of regulatory proteins, called transcription factors, that are unique to motor neuron identity. Next, the Whitehead team will use microarray technologies developed in the Young lab to identify the regulatory circuitry that is controlled by these transcription factors in both human and mouse embryonic stem cells, characterizing changes in these networks as the cells develop into motor neurons. The MIT group then will use these data to build a computer model of the gene activity that drives neural development, a model that the Whitehead and Columbia teams can subsequently verify with further laboratory experiments.

One component of this project will involve creating cells that are affected with the neurodegenerative condition spinal muscular atrophy (SMA), comparing them to normal cells in order to determine differences in gene expression patterns.

According to Gifford, “Even though we're using SMA as a model, we are hopeful this will yield clues for other neurodegenerative diseases,” such as ALS (Lou Gehrig’s disease), and even spinal cord injuries.

“I'm looking forward to working with this talented team,” says Young, who has long-standing collaborations with both Gifford and Jaenisch. “The Columbia University scientists have created the foundation for understanding the key steps in motor neuron development. This collaboration should further extend our understanding of this important area of neurobiology.”

“This project will likely have important clinical relevance in understanding the genetic basis of diseases of the motor neurons,” says Columbia’s Jessell. He and Wichterle were among the first scientists to successfully coax embryonic stem cells into forming motor neurons. “So far these diseases have been hard to understand because of our sketchy information on the normal molecular profile of motor neurons. We plan to change that.”

For detailed information on this project, visit http://www.stemcell.mit.edu/