Our lab is developing novel methods based on our published SPRITE approach to enable comprehensive mapping of RNA, DNA, and protein assemblies in the nucleus in a manner that generates direct information about 3-dimensional interactions and provides single molecule resolution of complexes along simultaneous information about transcription. We are using these methods along with genetic perturbation, biochemistry, and microscopy to dissect the role of ncRNA-mediated processes that link dynamic 3D nuclear structure and gene regulation in biology and disease.
Guttman Lab is investigating key mechanisms and unique roles that lncRNAs can play in gene regulation.
Dynamic assembly and disassembly of functional compartments.
Spatial amplification of regulatory information.
Spatial partitioning of the nucleus for efficient regulation.
Phase transitions and maintenance of regulatory states.
We are studying these properties within several key biological contexts, including:
- Chromosome-wide epigenetic silencing,
- Kinetic coupling of mRNA transcription and splicing
- RNA-induced aggregation and cellular toxicity in neurodegenerative disorders.
We expect that the insights derived will be broadly applicable to many other regulatory processes and will provide an important framework for understanding the roles that biochemical compartmentalization plays in the quantitative control of gene regulation.