Section The Center for Synthetic Regulatory Genomics (SyRGe) is tasked with development and application of revolutionary technology for making dramatic, coordinated changes to extensive gene loci, which will enable broad investigation of the function of regulatory sequences and foster translational applications to biotechnology, personalized medicine and gene therapy. Specifically, we will (i) design and synthesize over 1000 >100kbp constructs probing regulatory function at a carefully selected set of genes; (ii) develop a pipeline for their single-copy integration at any desired site genome-wide; (iii) survey libraries for effects on gene expression, chromatin features, and nuclear architecture; and (iv) develop global computational models to predict regulatory effects of sequence variation on gene expression. The Center will dramatically supersede present and predicted technologies for manipulation and assessment of regulatory genome function. This Center also incorporates a unique and highly successful outreach program whereby undergraduates from diverse backgrounds play a crucial role in genome assembly, as well as a new Fellows program to expose researchers and students from other fields to transformative new technology and facilitate its promulgation throughout the larger human genetics and genomics communities.

Public Health Relevance

Section The last decade in human genetics has seen an explosion in the number of variants linked to common human traits and diseases, but most of these variants lie in non-coding regulatory DNA. Although they likely act by altering levels or timing of expression of particular genes, the function of regulatory variation has remained difficult to characterize. This proposal includes basic mechanistic work utilizing highly efficient DNA assembly to over a thousand 100 kb gene regions varying in key candidate regulatory sequences to pinpoint sequence determinants specifying regulation of the gene in question, promising to dramatically improve our ability to interpret variation in non-coding regulatory elements and thereby decipher genome function.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project with Complex Structure (RM1)
Project #
1RM1HG009491-01A1
Application #
9488896
Study Section
National Human Genome Research Institute Initial Review Group (GNOM)
Program Officer
Gilchrist, Daniel A
Project Start
2018-06-12
Project End
2023-03-31
Budget Start
2018-06-12
Budget End
2019-03-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
New York University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016