Vijay Ramani is interested in the mechanisms that control how genes are turned on or off in our cells. He develops molecular techniques that make it possible to monitor gene activity at the level of single cells and single molecules. With these techniques, Ramani and his team study how changes in genome organization affect gene activity, or how the same gene may produce different RNA molecules under different conditions. In turn, the team hopes to parlay this information into a better understanding of the molecular steps that lead to disease or maintain the pluripotency of stem cells.
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Organs and tissues are made of heterogeneous collections of cells. Studying them in bulk preparations does not afford the resolution necessary to decipher the precise mechanisms underlying normal organ formation or disease progression.
Vijay Ramani has been at the forefront of a technological wave called single-cell genomics, which seeks to probe genome and cell function at the level of individual cells. He has developed a method based on DNA barcodes that allows scientists to analyze the genome and gene products of thousands of individual cells at once without having to physically separate the cells. With one version of this high-throughput approach, called SciHi-C, he produced maps of the genome’s 3D organization for more than 10,000 individual cells—100 times more than had been possible with previous approaches. Another adaptation of his single-cell technology is a drug-screening platform he calls SciPlex, with which he can evaluate the impact of thousands of drugs on gene activity in one experiment.
More recently, Ramani has become interested in probing gene activity at the single-molecule level. He is adapting existing sequencing technology to the high-throughput analysis of the diverse RNA molecules individual genes can produce in response to various stimuli.