NIH's National Human Genome Research Institute (NHGRI) will manage the five-year Molecular Phenotypes of Null Alleles in Cells (MorPhiC) program.

Phase I will focus on 1,000 protein-coding genes. Its goals are threefold: exploring ways to inactivate, or "knock out," gene function; developing molecular and cellular models of human tissues and developmental stages; and developing reproducible approaches to cataloging gene function.

Projects will use null alleles -- gene versions that do not make functional proteins. Null alleles allow a given gene's function to be better deduced by studying its resulting phenotype.

Over 6,000 of the estimated 19,000 protein-coding genes have not yet been well studied. Among those genes studied, few of their functions are well characterized. Cataloging these genes is challenging, as many have multiple functions and behave differently depending on the cell type in which they occur. Also, genes may turn on or off depending upon the cell's environment, age, and relationship to surrounding cells.

The MorPhiC program's research will use cell culture models such as organoids, miniature 3D models composed of multiple human cell types that mimic real tissues and organs. Pending phase I's success, phase II may characterize a larger human gene set.

"The function of thousands of genes is still a mystery, and they likely serve vital biological roles," NHGRI program director Colin Fletcher, PhD, 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."