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Molecular Phenotypes of Null Alleles in Cells (MorPhiC)

Phase 1

MorPhiC aims to develop a consistent catalog of molecular and cellular phenotypes for null alleles for every human gene by using in-vitro multicellular systems.

The 2020 NHGRI Strategic Vision laid out a set of “bold predictions for human genomics by 2030” that included: “The biological function(s) of every human gene will be known; for non-coding elements in the human genome, such knowledge will be the rule, rather than the exception.” Systematically obtaining genome-wide information about gene functions is critical for elucidating the roles and relationships of genes and regulatory elements in pathways and networks, which is one of the compelling genomic research projects outlined in the NHGRI Strategic Vision.

Program Goals

Conceived as one way to address this element of the Strategic Vision, MorPhiC aims to develop a consistent catalog of molecular and cellular phenotypes for null alleles for every human gene by using in-vitro multicellular systems. The catalog will be made available for broad use by the biomedical community. The program will start with a Phase 1 to optimize available methods to create null alleles and measure their phenotypic effects in a target subset of 1,000 protein coding genes across the program. Phase 1 will also assess the scale limitations of such methods, develop common data formats and establish use cases for this catalog.

Systematically obtaining information about the molecular and cellular phenotypic effects of gene knockouts for all human genes would provide wide-ranging insights into their biological function. Such data would provide a foothold for understanding the mechanisms through which genes act to produce phenotypes and would help elucidate the roles and relationships of genes and regulatory elements in pathways and networks.

MorPhiC Phase 1 will include three components:

  • Data Production Research and Development Centers will develop diverse systems and assays and explore and compare approaches to produce MorPhiC data at scale, and to maximize its informativeness.
     
  • Data Analysis and Validation Centers will undertake applicant-proposed analyses of the data in order to characterize its quality and utility for multiple purposes.
     
  • There will be a Data Resource and Administrative Coordinating Center.
     

All components will work together to ensure that the data are informative, of high quality and useful to the community.

See the MorPhiC Concept Document and Concept Clearance.

Funding and Grants

Active

At this time, there are no current funding opportunities. 

Expired

Molecular Phenotypes of Null Alleles in Cells (MorPhiC) Phase I: Data Analysis and Validation Centers (U01 Clinical trials not allowed)
RFA-HG-22-019
Expiration Date: November 2, 2022

Molecular Phenotypes of Null Alleles in Cells (MorPhiC) Phase 1: Data Production Research and Development Centers (UM1 clinical trials not allowed)
RFA-HG-21-029
Expiration Date: November 2, 2021

Molecular Phenotypes of Null Alleles in Cells (MorPhiC) Phase 1: Data Analysis and Validation Centers (U01 clinical trials not allowed)
RFA-HG-21-030 
Expiration Date: November 2, 2021

Molecular Phenotypes of Null Alleles in Cells (MorPhiC) Phase 1: Data Resource and Administrative Coordinating Center (U24 clinical trials not allowed)
RFA-HG-21-031
Expiration Date: November 2, 2021

Grantee Information

ComponentPrincipal InvestigatorInstitutionTitleRole/Mechanism
Data Production Research and Development Centers (DPCs)Paul RobsonJackson LaboratoryJAX MorPhiC Data Production CenterUM1 HG012651
Danwei HuangfuSloan Kettering InstituteCenter for scalable knockout and multimodal phenotyping in genetically diverse human genomesUM1 HG012654
Mazhar AdliNorthwestern UniversityMolecular and cellular characterization of essential human genesUM1 HG012649
Luke GilbertUniversity of California, San FranciscoSpatial multiomic mapping of gene function with CRISPRoffUM1 HG012660
Data Resource and Administrative Coordinating Center (DRACC)Stephan SchurerUniversity of Miami School of MedicineMorPhiC Data Resource and Administrative Coordinating CenterU24 HG012674
Data Analysis and Validation Centers (DAVs)Jesse EngreitzStanford UniversityMorPhiC: Constructing a Catalog of Cellular Programs to Identify and Annotate Human Disease GenesU01 HG013176
Sheng LiJackson LaboratoryMulti-omic phenotyping of human transcriptional regulatorsU01 HG013175
Wei SunFred Hutchinson Cancer CenterStatistical Methods for Inferring Gene-Phenotype Associations Using Omic Data from Gene Knockout and Human Phenotype StudiesU01 HG013177

Contact

Send questions to morphicprogram@mail.nih.gov.

Websites

Molecular Phenotypes of Null Alleles in Cells (MorPhiC)
morphic.bio
Molecular Phenotypes of Null Alleles in Cells (MorPhiC)

Program Staff

Adam Felsenfeld, Ph.D.
Adam Felsenfeld, Ph.D.
  • Program Director
  • Extramural Programs Branch
Colin Fletcher, Ph.D.
Colin Fletcher, Ph.D.
  • Program Director, The Knockout Mouse Project (KOMP)
  • Division of Genome Sciences

Last updated: March 11, 2025