Growing up in a remote part of India, Akanksha Thawani (she/her) was captivated by math and physics and how they could be harnessed to solve real world problems. But midway through her mechanical engineering degree at the Indian Institute of Technology Bombay, after spending months on a project trying to make Dyson vacuum cleaners run more quietly, she realized this was not the type of science she wanted to do. She wanted to be in a field where her curiosity had more room to roam free.
Reluctantly, she followed a professor’s advice to try biology, a subject with which she’d never really clicked. But after building a minnow-sized, whip-tailed robot to study how bacteria like E. coli swim, she was hooked.
For her Ph.D., Thawani moved to the U.S. to apply her engineering brain to the study of microtubules — the structures that give a cell its shape and organization — at Princeton University. Through that work she met Eva Nogales, a structural biologist who had worked closely with Jennifer Doudna at the University of California Berkeley to figure out the 3D structure of CRISPR/Cas9, the Nobel Prize-winning workhorse of the genome-editing world.
Determined to do something with similar impact, Thawani joined Nogales’ lab for a post-doc, and quickly zeroed in on retrotransposons — RNA-based macromolecules that form the dark matter of the human genome. They have the somewhat mysterious ability to copy themselves into new sites, which can be a problem if they disrupt critical genes, but has also made them an attractive target for harnessing into directable DNA-inserting tools.
“It was clear to me that they will be the next CRISPR,” Thawani said.
Although a lot of work had been done to sequence retrotransposons, what was missing was structural and biochemical information about how the molecules move around the genome. Starting with Line1, a retrotransposon that makes up one-third of the human genome, Thawani successfully ascertained its 3D structure and uncovered new insights about what kind of DNA architecture it needs to perform its self-copying stunt — earning her a first-author paper in Nature.
Now, her goal is to shed light on the mechanistic underpinnings of other retrotransposon systems, in the hopes of finding one that is more amenable to being programmed to insert large stretches of DNA into specific sites in the genome. “If we want to engineer them, we need to first understand them,” Thawani said.
—Megan Molteni
