In 2016, when Google’s AlphaGo bested Lee Sedol, the Go champion of the world, Julia Joung breathed a sigh of relief. By then, she was partway through a Ph.D. at MIT, working in the world famous Feng Zhang lab as a biological engineer. But she’d spent much of her childhood in Taipei training to play the board game professionally. Lee was one of her idols. She felt like she’d dodged a bullet. Then again, playing thousands of games of Go had prepared her for life as a scientist.
“You learn early on how to deal with failure,” Joung said. “And as you become better and better you have to do more and more learning on your own. That’s a skill that really transfers to science.”
“As you become better and better you have to do more and more learning on your own. That’s a skill that really transfers to science.”
Joung, a self-described “late bloomer,” has applied her independent learning streak to develop CRISPR screens to illuminate biology. Genetic screening allows scientists to simultaneously probe every gene in the genome for its role in a specific process. CRISPR supercharged these efforts.
In Zhang’s lab, Joung designed a new kind of CRISPR activation screen that could investigate the vast non-coding regions of the genome, which scientists are only just beginning to understand.
“We really need something like a genome-wide screen to identify the ones that are actually useful and not junk and actually tie them to particular phenotypes,” Joung said. Applying that technique to T-cell-treated melanoma cells, Joung identified genes these cancers sometimes switch on, allowing them to develop resistance to CAR-T and other immunotherapies.
She hoped to next use such screens to investigate Alzheimer’s — but she realized the existing cell models weren’t compatible with the approach. So instead, she designed a reverse screen that generated a collection of transcription factors — the genetic programs that stem cells execute to differentiate into various brain tissues.
In a forthcoming paper, Joung expanded that work to create a vast transcription factor atlas, handing scientists a starting point for engineering nearly all human cell types.
Joung credits Zhang with creating an environment that encouraged swinging for the fences. She’s taken that attitude to a postdoc in the Jonathan Weissman lab at the Whitehead Institute, where she plans to apply her skills to better understand how translation is regulated in stem cells.
“We’re sort of in a golden age of genetic screens,” Joung said. “With DNA sequencing and synthesis technologies, there is a lot of open space out there.”
— Megan Molteni
