By Michaela Herrmann
Every year, Yale’s Faculty of Arts and Sciences hires dozens of exceptional scholars in academic departments across the sciences, humanities, and social sciences. This series profiles six of the faculty joining the FAS in the 2024—25 academic year, highlighting their academic achievements, research ambitions, and the teaching they hope to do at Yale. Learn more about the incoming ladder faculty and multi-year instructional faculty joining the FAS.
For Ailong Ke—a field-leading biophysicist and biochemist working at the forefront of RNA and CRISPR-Cas technologies—curiosity is what it’s all about.
“I actually didn’t come into RNA biology or CRISPR-Cas for the sole purpose of curing disease or developing technologies,” he says. “I really just followed my curiosity, and I think this is a beautiful example that following your curiosity in science leads to something great.”
Ke’s drive to understand RNA—one of the most important molecules in our cells, responsible for a variety of processes like gene expression and carrying biological information—led him to Yale’s Faculty of Arts and Sciences. He joins the Department of Molecular Biophysics and Biochemistry as a Professor, where he will start a new lab and continue his exploration of the mechanisms underlying RNA and other nucleic acids.
“I think people who apply structural biology to mechanistic studies have a unique advantage because we basically understand our systems inside out and in high resolution—to the point that we understand how this molecular interaction works, what it means, and how we can make use of that interaction,” Ke explains. “A lot of insights there can be converted into potential applications.”
Ke is particularly looking forward to exploring those applications side-by-side with clinicians, an opportunity Yale should offer in spades. “For a lot of technologies, due to our limited background in medicine, biophysicists and biochemists may not know the best applications for them. And on the other side, clinicians may not know that there is a tool already invented in the lab for the diseases they want to cure.” Ke is already exploring collaboration opportunities with several clinicians on campus. “Hopefully we’ll be able to take the inventions from the lab and bring them to clinics and try to benefit the patients.”
The primary focus of Ke’s career thus far has been the RNA molecule. His research is deepening scientific understanding of the CRISPR-Cas system: a natural cellular immune response found in bacteria that can be repurposed by researchers to target and modify DNA sequences, a process called genome editing. “These systems rely on RNA as the guide,” Ke says, “so I try to understand how RNA guides the process and how it regulates the enzyme activities. I also try to be creative and try to do some synthetic biology, to generate macromolecules that perform tricks that have not been invented by nature.”
RNA is at the “center stage” of research and medicine these days, Ke says, and he hopes his new position will allow him to attract the talent and funding to keep pushing the research envelope. The rapid development of RNA vaccines and CRISPR-Cas makes him feel like he “hit the jackpot” with his research interests, especially with his cutting-edge work on genome editing with different CRISPR-Cas systems.
It’s important to be aware of the potential downsides of using CRISPR-Cas for genome editing, Ke points out, while also finding ways to demonstrate the powerful potential of the technique. “With genome editing, we’re excited about it, but we’re also wary about its potential risk. Nothing is 100% accurate, and off-targeting by a CRISPR editing tool could be pretty detrimental. There are also some ethical issues with it,” he explains.
“But I think targeting serious diseases like cancer will actually alleviate some of the concerns that people may have about gene editing tools, because it is a very serious and grave disease, and we need powerful tools to target it.” Helping develop tools that can assist with cancer treatments has been a major project in Ke’s lab, and one he plans to continue at Yale. “Once we realize the great potential in these tools, I think it would be a missed opportunity not to follow them.”
Ke is also enthusiastic about continuing to teach the next generation of scientists, one of his favorite parts of being a member of faculty. “Fundamentally, we’re trainers,” he says of his time spent in the lab with students. “We want to see the next generation of scientists flourish.” The best parts of Ke’s daily work as a professor? “Interacting with the trainees in the lab on a day-to-day basis—understanding and taking a peek at their new results, trying to help them overcome the technical hurdles, and making new discoveries together. And the second is to teach the undergraduates and basically carry the knowledge to the next generation.”
He has about a year to establish his lab, recruit trainees, and write grants that will set his operation up for a strong start that can be sustained over time. Ke will also soon decide what courses to offer—a comprehensive overview of RNA is an option, as well as classes on CRISPR-Cas, biochemistry, and biotechnology.
After that, it’s off to the races.
“Yale has been a stronghold in RNA biology, structural biology, and molecular mechanisms,” Ke says of his new department. “I really have a high regard for the research at Yale, so this is a great opportunity to interact with colleagues I respect a lot on a daily basis, especially people in the RNA biology field.”
The combination of working with students and being inspired by his colleagues should make for a busy and fulfilling role. “There’s this new trend to essentially do structural biology inside the cell, in situ structural biology, which will allow researchers to understand where the molecules are inside the cell, what they interact with, and how they carry out their function in their native setting,” Ke says, clearly thinking about the potential for major developments in the field. “I think this is going to lead to exciting discoveries. Structural biology could become the forefront of research tools and drive discovery, and I want to be part of that.”
Work in structural biology by colleagues Yong Xiong and Kai Zhang, both part of the Department of Molecular Biophysics and Biochemistry, is particularly impressive to Ke, and he looks forward to being part of Yale’s community of other exceptional scholars. “There are a few topics that are really, really exciting incubating in the department and around Yale, and I want to be part of that. I’m looking forward to pushing the envelope of mechanistic biology and structural biology.”
Image 2: A summary of Ke’s recent research on IscB, an RNA-guided endonuclease.
Image 3: Ke and members of his previous lab.