NEW YORK – The National Institutes of Health announced on Tuesday it is launching a program to systematically establish the function of each human gene and to catalog the molecular and cellular consequences of inactivating each one.
Initially focusing on 1,000 protein-coding genes, the first phase of the Molecular Phenotypes of Null Alleles in Cells (MorPhiC) program, managed by the National Human Genome Research Institute (NHGRI), will serve as a pilot phase with three goals: exploring multiple methods of knocking out gene function; developing molecular and cellular systems that model multiple human tissues and developmental stages; and developing molecular and cellular approaches to catalog gene function that other researchers can reproduce.
Currently, just over 6,000 of the estimated 19,000 protein-coding genes have been well studied, and among those, only a subset of their functions is well characterized.
"The function of thousands of genes is still a mystery, and they likely serve vital biological roles," Colin Fletcher, NHGRI program director in the Division of Genome Sciences, said in a statement. "Understanding fundamental biology can help us figure out why certain diseases occur and how can we develop drugs to target and treat those diseases."
MorPhiC will initially be funded for five years with a total of $42.5 million, pending the availability of funds.
Projects funded by MorPhiC will explore protein function by generating null alleles, or versions of genes that do not make functional proteins.
This effort is complicated by the multifunctional nature of many genes, whose behavior may change depending on the cell type in which they are expressed, and which may or may not be active in a given tissue, depending on factors such as cell signaling, environment, and age.
Research within the program will take place in various cell culture models, including organoids — 3D "mini-organs" composed of multiple cell types and which mimic the functions of the tissues and organs found in the human body.
Pending the success of Phase 1, the NIH plans to initiate a second phase in a larger set of human genes.
Five researchers have won Phase 1 funding for the MorPhiC program. They are Mazhar Adli of the Northwestern University Feinberg School of Medicine, Luke Gilbert of the University of California, San Francisco, Danwei Huangfu of the Sloan-Kettering Institute for Cancer Research, Paul Robson of Jackson Laboratory, and Stephan Schürer of the University of Miami.
"MorPhiC is meant to add another layer of functional information between the gene knock-out at the DNA level and the organism-level effects," Adam Felsenfeld, also an NHGRI program director in the Division of Genome Sciences, said in a statement. "We want to catalog the effects of knocking out each gene within cells and — together with information from other studies — use that to understand how genes function to produce an organism."