Adli, of the University of Virginia School of Medicine’s Department of Biochemistry and Molecular Genetics, has developed a way to track genes inside living cells. He can set them aglow and watch them move in three dimensions, allowing him to map their positions, much like star charts record the shifting heavens above. And just as the moon influences the tides, the position of genes influences the effects they have; thus,
«This has been a dream for a long time," Adli said. «We are able to image basically any region in the genome that we want, in real time, in living cells. It works beautifully. … With the traditional method, which is the gold standard, basically you will never be able to get this kind of data, because you have to kill the cells to get the imaging. But here we are doing it in live cells and in real time.»
DNA is often depicted as tidy strands stretched out in straight lines. But in reality, our DNA is clumped up inside the nuclei of our cells like cooked spaghetti. «We have two meters of DNA folded into a nucleus that is so tiny that 10,000 of them will fit onto the tip of a needle," Adli explained. «We know that DNA is not linear, but forms these loops, these large,
Thinking about DNA as a neat line, he noted, can create misconceptions about gene interactions. Two genes that are far apart in a linear diagram may actually be quite close when folded up inside the cell’s nucleus, and that can affect what they do. He used a map analogy: «That’s how we believe an element that appears to be in Los Angeles is regulating an element in Virginia — [when the DNA is folded up,] they’re not actually that far apart.»
Adli’s new approach, developed in conjunction with colleagues at UVA and the University of California, Berkeley, uses the CRISPR gene editing system that has proved a sensation in the science world. The researchers flag specific genomic regions with fluorescent proteins and then use CRISPR to do chromosome imaging. If they want, they can then use CRISPR to turn genes on and off, using the imaging approach to see what happens.
The new method overcomes longstanding limitations of gene imaging. «We were told we would never be able to do this," Adli said. «There are some approaches that let you look at
The business of growing cells just to kill them is both