Through as long as 11 years in obscurity, the team of Chaopei Liu successfully solved a major issue that awaits solutions for 30 years in the fields of chromatin structure and DNA replication, and their research achievements have been published in the journal Science. Meanwhile, reviewers highly praised the meaning of this research. Chaopei Liu, the first author and corresponding author, said in WeChat Moment “Although it is a little late, the harvest is always the result of persistence.”

11 years of “persistence in scientific research”

In 2010, after graduation, Chaopei Liu joined Institute of Biophysics, Chinese Academy of Sciences, and conducted post-doctoral work in the lab of Ruiming Xu, an outstanding expert in epigenetics and structural biology.

2 years later, Chaopei Liu successfully analyzed the structure of histone variants and chaperone protein complexes, solved the problem of variant recognition, a puzzle in the field for many years, and published the results in the journal Nature Structural & Molecular Biology.

In the context of the win of the first battle, he immediately challenged the “top issue” in this field, namely deconstruction of Chromatin Assembly Complex 1 (CAF-1) complex, and made a “5-year plan”. He thought that deciphering the structure of CAF-1 complex can greatly contribute to the understanding of nucleosome assembly.

In the early stage of research, he conducted screening of substantial crystal conditions on CAF-1 constituted by different fragments according to the “segmentation” method, and successfully analyzed the 3.5 Å crystal structure of the core part of CAF-1, revealing its soft structure. This achievement also brings confidence to the team and made them feel that there was a good chance of success.

But soon after, the research has been in the limbo, and the “5-year plan” transformed into “11 years of persistence”.

Mining treasury in “junk data”

“Visualization is pivotal in structural biology, and structure and action of mechanism are difficult to be understood under obscure view”, said Chaopei Liu. This study involves the transfer and modification of histone proteins and multiple factors, so the difficulty of research increases exponentially.

After a “failure” experiment, Chaopei Liu occasionally found the resolution of some small fragmented particles present a sign of improvement when processing data. Accordingly, he boldly conjectured that DNA may act as a buffering agent in this process.

He immediately assayed DNA fragments with different lengths. Later, he observed clear CAF-1 image under cryoelectron microscope when testing 30-bp DNA, and unexpectedly observed the image of “right-handed helix nucleosome intermediate state” when testing longer DNA at 147-bp.

This inspiration came out of the blue and enlightened him to dig out treasury from “junk data”.

Through 10-year exploration, in 2022, Chaopei Liu’s team ultimately submitted paper to Science. Despite the rejection letter, the paper still aroused strong interest from reviewers, because this is a groundbreaking discovery. Hence, reviewers asked them to provide more detailed data proof for re-submission.

After one year of revision, their second submission was finally accepted, and received high praise towards the research achievement from reviewers---“This research expands a new research field.” Just two months later, the paper was published in the journal Science.

“Solving one question doesn’t mean the end of research, but will elicit more new questions and perspectives”, said Chaopei Liu. He will continue to conduct in-depth studies in this field with the scientific philosophy of “Better to drill a well at one spot than to dig a hole everywhere”.