NEW YORK (GenomeWeb) – The National Institutes of Health has pumped $64 million into six research institutions to create a network and database of human cellular responses that will support scientists developing new treatments for diseases, NIH said on Thursday.
The funding will establish six centers that will work together to create the Library of Integrated Network-based Cellular Signatures (LINCS), which will catalog and analyze cellular functions and molecular activities in response to perturbing agents. The scientists in the network will measure molecular responses in cells and look for patterns, or signatures, in those responses. The data housed in the LINCS database will be made freely available to the research community.
"The simplest way to think about signatures is essentially as broad common patterns, as well as uncommon behavior, in how cells respond to being exposed to various small molecules, genetic perturbations, or genetic changes," Ajay Pillai, program director in the Division of Genome Sciences at the National Human Genome Research Institute, said in a statement. "For example, you could figure out patterns of toxicity of potential new drug compounds by looking at cellular responses and finding common responses to other known toxic molecules."
The LINCS program has completed a prototype phase, which has already generated "meaningful results," NIH said. For example, a research team has used the data to identify the role of a transcription regulator in cancer, and another group reported that the LINCS approach of measuring a wide range of cell responses to drugs was more accurate than conventional drug-potency tests.
Harvard Medical School researchers will receive $12.9 million to develop new measurement methods and computer algorithms to detect and analyze perturbations induced by therapeutic drugs in healthy and diseased human cells, NIH said. The Harvard team wants to shed light on the interrelationships of proteins in complex diseases, which could be useful in developing new approaches to drug discovery and personalized treatments.
Oregon Health and Science University scientists will receive $10.3 million to study how malignant cells are controlled by their microenvironments, and will provide measurements of the impacts of thousands of these environments on cellular phenotypes, protein make-up, and gene expression readouts in cell lines.
A Broad Institute team will use $12.6 million to create a genome-scale catalog of the consequences of cellular perturbation. It plans to generate about 1,000 gene-expression readouts for each perturbation and more than 1 million profiles of how genes are expressed in cells. This catalog would enable researchers to query the database to learn the effects of blocking or overexpressing a particular gene.
Another team at Broad will receive $8.9 million to study the most basic levels of cell disruption, phosphorylation-mediated signaling, and epigenetics. This team will test more than 11,000 perturbational conditions in several cellular model systems.
Scientists at the Icahn School of Medicine at Mount Sinai will use $11.4 million to develop cell signatures to predict adverse events and identify drugs that might lessen those side effects. The team will use the US Food and Drug Administration's Adverse Event Reporting System database to identify adverse events in heart, liver, and neuronal function, and search for drugs to mitigate these events.
The University of California, Irvine will use $8 million to use perturbations to study an array of human brain cells, with the aim of identifying targets for developing drugs against neurodegenerative diseases.