A National Institutes of Health (NIH) grant presented to investigators at the Cedars-Sinai Regenerative Medicine Institute is intended support Cedars-Sinai’s participation in a consortium focused on gathering and analyzing data to provide a “global view” of neuromuscular disorders.

In a Cedars-Sinai news release, Clive Svendsen, PhD, professor and director of the Board of Governors Regenerative Medicine Institute, principal investigator of Cedar-Sinai’s part of the study, explains, “We will be working as part of an NIH initiative to create databases of disease ‘signatures’ by generating and analyzing thousands of data points…”

The release notes that the grant is part of an NIH initiative called the Library of Integrated Network-based Cellular Signatures, or LINCS program, which is focused on developing a “library” of molecular signatures that describes how different cells respond to proteins, genes, chemicals, and essentially anything that may come in contact with or change the cell or its activity.

Cedars-Sinai is a member of the NeuroLINCS group, studying motor neuron disorders, including amyotrophic lateral sclerosis (ALS) and spinal muscular dystrophy. According to the release, researchers at the University of California Irvine will coordinate the NeuroLINCS study, with additional collaborators hailing from the Gladstone Institutes at the University of California, San Francisco, Johns Hopkins University, and the Broad Institute.

NeuroLINCS is one of six consortiums recently funded through NIH’s LINCS program to study diabetes, cancer, and other diseases using cell lines and specialized stem cells known as induced pluripotent stem cells. The release reports that the Board of Governors Regenerative Medicine Institute was asked to provide the stem cells for all of the consortiums. The cells are produced in the Regenerative Medicine Institute’s Induced Pluripotent Stem Cell Core Facility, directed by Dhruv Sareen, PhD, assistant professor of biomedical sciences and faculty research scientist with the Department of Biomedical Sciences.

Together, the release says, Cedars-Sinai and the Regenerative Medicine Institute will also play a key role in the data generation phase of the study. New technology reportedly allows scientists to “mine” data on a large scale, such as measuring millions of proteins in a single sample. Jennifer Van Eyk, PhD, director of Cedars-Sinai’s Advanced Clinical Biosystems Research Institute and the Erika J. Glazer Chair in Women’s Heart Health, will serve as co-principal investigator of Cedars-Sinai’s part of the study and provide protein analysis for all NeuroLINCS collaborators. The release states that other expert teams will gather data about genetic material and the way in which genetic information is relayed to proteins within cells.

Svendsen points out that the data analysis teams will ultimately collaborate in order to create computer programs to assemble all of the information.

“We may be looking at many thousands of data points, but using algorithms to create a ‘cloud’ of information, we expect to see a ‘signature’ emerge that shows us the relationships between proteins, genes and RNA in the cell. There will be a specific signature for healthy controls and a different one for the disease, such as Lou Gehrig’s,” Svendsen says.

Svendsen adds that once this has been accomplished, investigators will work to “punch holes” in the disease signature by hitting the cell with a small molecule to see how the cloud of information changes. The investigators’ ultimate aim, Svendsen explains, is to “morph the disease cloud back into a healthy cloud. But right now, we don’t know what the disease state is. This is what we want to find out.”

Svendsen goes on to emphasize the mutual interest he shares with Sareen in developing personalized medicine for patients with neurodegenerative diseases. He adds that investigators want to create in a dish, the motor neurons that mirror an individual patient’s disease to allow for investigators to see how quickly or slowly degeneration occurs.

“…Through the LINCS grant, big data technology enables us to explore motor neurons in greater deal and gives us a much more sophisticated way of producing and analyzing these personalized models,” Svendsen says.

Source: Cedars-Sinai Regenerative Medicine Institute