Think about untangling a ball of yarn hundreds of feet long and trying to re-wind it in exactly the same way — that’s essentially what a cell does with its DNA every time it divides. Now, new research from assistant professor Aaron Streets’ bioengineering lab attempts to make sense of this process, using a novel technique for unraveling and imaging lengthy strands of DNA. Their microfluidic platform, µDamID (or MicroDamID), can trap a single cell and then apply DNA sequencing to read exactly which sequences are where inside of it.
While microscopy still represents the gold standard for validating where molecules are in a cell, high-throughput DNA sequencing technologies have allowed researchers to sequence the DNA and RNA from single cells, providing rich information about the information that is encoded in our genome. Until now, it’s been very difficult to take a picture of a single cell with a microscope and then pick that cell from the microscope slide and sequence its DNA.
“MicroDamID is a technique that takes a picture to ‘see’ where proteins are binding to DNA inside the cell, then sequences the DNA at those same binding sites from the same single cell to reveal where they are in the genome,” said bioengineering Ph.D. student Nicolas Altemose. “It’s hard enough to do one or the other, but this tool allows us to measure and understand both the spatial and the linear organization of the DNA. It improves our ability to create these protein-DNA binding maps to study how DNA is regulated in the nucleus.”
Possible applications of the technology include areas such as meiotic recombination and chromosomal segregation, as well as studying other key processes that differ among individual cells.