Recently, Alibaba DAMO Academy announced their 2022 young fellows. Rui Bai from Westlake University was the youngest among the 15 chosen this year. She was named a fellow for “participating in and leading the world's only spliceosome series covering the complete RNA cycle, bringing new ideas to the study of related genetic diseases and cancer mechanisms”.

Exploration

Bai started her work on the spliceosome the day she joined Prof. Yigong Shi’s lab.

Studying the spliceosome is crucial to understanding human health. Studies show that about 35% of human genetic diseases are caused by abnormal splicing. However, the spliceosome is also known as the most complex ultra-macromolecular complex in cells, and it is a global challenge to decipher its structure.

According to Bai, there are in total four research groups in the world that can conduct biological research on the spliceosome structure. “My brain went blank” when she found out this would be her research area. Yet she was grateful for the encouragement offered by her advisor. “This is the kind of challenge we should take on. If those of us from Tsinghua don’t even have the guts to do it, who will?”

That courage came with Bai to Westlake. Every morning, she walks into the lab refreshed, and works till after midnight. Over the past seven years, she has taken her thoughts on experiments from the lab to her home, and vice versa. She still gets butterflies in her stomach when waiting for test results. “That’s how I feel every day, even just yesterday.”

“To some, my research might seem boring - I do practically the same experiment every day. But I see the beauty in it. Every day I would design the experiment differently, and every day the result would come out differently. In this process, I come across things that weren’t known to the world before. It feels like I am creating knowledge, and it is fun.”

Thanks to her “participation and leadership in the world's only spliceosome series covering the complete RNA cycle,” and “bringing new ideas to the study of related genetic diseases and cancer mechanisms”, Bai was named as a 2022 Alibaba DAMO Young Fellow.

Bai has already published six papers in Science and three in Cell as a first or co-first author. Before the DAMO fellowship, she was also chosen for the 2020 L’Oréal-UNESCO For Women in Science International Rising Talents program, and was a finalist for Rising Talent from China in 2018.

Shi described her as “one of the finest students in my lab, and one of the best young scientists in the world. Her intelligence, independence, the depth of her critical thinking and her perseverance in science goes far beyond her peers. I have no doubt that she is an outstanding scientist, and we expect to see research with profound influence from her efforts.”

Challenges

Back in 2020, Bai was trying to design a series of biochemical experiments to verify the lab's discovery on the "molecular clock" in RNA splicing. ATPase/helicase, the power kinesin, is needed in each state of the spliceosome transition to help it fold and assemble. It controls the changes of status as well as corrects the process of RNA splicing, hence it is known as the “molecular clock”. Bai’s team already located it in the RNA, yet more biochemical experiments were needed to prove its existence.

Then they hit a wall. The pandemic slowed everything down. To Bai, it was as if she knew what was behind that closed door, but “it refused to open with all the keys I tried”.

Spliceosomes are intricate complexes made up of hundreds of proteins. It is hard enough to prove the functions of such complex, and there aren’t many relevant studies available yet. Bai had to cross the river by feeling the stones. That was the first time she worked on it, and the mutations and complexity in testing were exacerbated by the dynamic itself. “It was tremendously captivating, but extremely difficult if you were looking in the wrong direction,” she said.

The pressure of the bottleneck affected her sleep for more than six months. But she never stopped believing that it was a matter of finding the right perspective. Bai threw herself into her work with the help of her advisor and colleagues.

When she got really stuck, she took two days off and indulged herself with good food and reality shows. Perhaps it was the change in mood, or the failure over the past six months just reaching the tipping point. But when she returned to the lab after the break, an idea came to her, and unlocked the door she’d be knocking on.

In the end, she published an article titled “Mechanism of Spliceosome Remodeling by the ATPase/helicase Prp2 and its Coactivator Spp2” in Science. She was the first to illustrate the structural basis of the ATP hydrolase/helicase Prp2 and its activator Spp2. She clarified the molecular mechanism of Prp2’s unidirectional movement on the precursor messenger RNA and provided answers to a series of important scientific questions about the RNA splicing process.

While Shi said she could be “stubborn”, Bai sees it slightly differently. “It’s a neutral word. I would insist on things that I know for sure, and thanks to that perseverance, I am where I am today. I could be completely lost, had I given up back then.”

Thanks to her determination, Bai now stands at the front lines of hacking a global challenge.

Noise

Noise was a part of her life before Bai became an outstanding young scientist.

When selected for the Woman in Science International Rising Talents program in 2020, someone left a comment under the news: You’d be nothing if male scientists were part of the game.

Time and time again, she was told “women don’t need a Ph.D. degree” as she proceeded with her doctoral and postdoctoral work.

Back in high school, when Bai chose to major in STEM courses, she was told “girls would fall behind as soon as they enter senior high school.”

Bai chose to ignore others on the matters she believed in. “For me, it’s clear as day: No one else’s opinion is worthy enough for you to spend your life on. I ignore unfriendly comments. Over time, they stopped trying to convince me.”

The noise failed to stop Bai from becoming an outstanding scientist, but it did contribute to the unreasonable perceptions and prejudice against female scientists. This is also known as the “leaky pipeline” syndrome in the academic world.

Ben Barres, an American neurobiologist, decided to undergo gender alteration surgery at the age of 43 and became male. He later stated in an autobiography that the scarcity of women in science was not a matter of capability, but because they suffered more prejudice, obstacles, and pushback.

To tackle this, the Westlake Education Foundation launched the Westlake Female Scientists Development Program this March, hoping to support more female scientists and encourage them to bravely pursue excellence.

To Bai, there is no end to the path of science. Once the old problem is solved, a new one appears. She will become an independent lab manager, have her own team, and continue exploring the structure of the spliceosome and the molecular mechanism of RNA splicing. On the path of science only perseverance and creativity can get us closer to the true nature of life.