Project Grant 2243665

This $2.11 million project grant from the National Science Foundation's Division of Emerging Frontiers, under the Biological Sciences federal grant program (CFDA 47.074), will fund research at Emory University and the University of Tennessee from March 2023 through February 2027 to rationally design long noncoding RNAs (lncRNAs) for epigenetic signal amplification. The researchers will define the minimal features required for large-scale silencing mediated by lncRNAs, building on the well-characterized XIST lncRNA responsible for X chromosome inactivation in females. They will test lncRNA repeats and silencing ability in mammalian cells, integrate synthetic lncRNAs to silence autosomal loci using CRISPR, and create a standalone silencing system in yeast to further optimize the system. The goal is to gain fundamental understanding of how lncRNAs can exert silencing effects at a chromosomal scale despite low expression, and to validate, challenge, and expand understanding of lncRNA mechanics. Outcomes may include defining minimal components and lncRNA levels required for stable, specific epigenetic regulation. This research could enable broadly applicable lncRNA biotechnology with implications for bioengineering.