Toward High-Throughput and Multiplexed Imaging of Genome Organization

Dr. Eric Joyce from the Department of Genetics at the University of Pennsylvania was awarded The President's Innovation award at the annual Society of Biomolecular Imaging and Informatics meeting held in Boston, September 2016. Chromosome interactions are a fundamental aspect of nuclear organization that can activate and silence genes or even direct chromosome rearrangements. However, the molecular mechanisms underlying how chromosomal segments find each other and form stable interactions within cells remain unknown. To address this gap, we have recently developed two technologies that use fluorescent in situ hybridization (FISH) to interrogate chromosome positioning at single-cell resolution. The first is a technology for high-throughput FISH, and the other, called Oligopaints, is a new type of probe that reduces the cost and increases the resolution of FISH. Here, I review our use of these two technologies to uncover and characterize the molecular mechanisms that govern chromosome pairing in Drosophila. I further describe how these methods should benefit a broad spectrum of research fields, including those focusing on chromatin looping, compaction, replication, homologous recombination, and DNA repair.