Dysregulation in protein production can have profound effects on human health, leading to diseases such as diabetes, heart disease, and cancer. In their search to understand how and why protein synthesis can go awry, scientists are turning to ribosomes, organelles that translate messenger RNA (mRNA) into the nucleotide chains that make up proteins.
Through a technique called ribosomal profiling, scientists gain insight into how protein synthesis is initiated and regulated — with an eye toward developing therapeutic tools to re-stabilize protein synthesis that has gone off-kilter. Ribosomal profiling assesses the location and spatial density of ribosomes on a strand of mRNA, which allows scientists to quantify, among other measurements, the rates at which proteins are synthesized.
When Erica Shu was beginning her doctoral research at Cornell University with advisor Shu-Bing Qian in 2016, the process to acquire this data was slow and laborious, and results often weren’t reliably reproducible — results could only be replicated across samples 60% of the time. In addition, the available technology required such large samples that analyzing tissue from patient biopsies wasn’t always possible.
“It took a lot of work,” says Shu, now teaching faculty in the UW–Madison Department of Biochemistry. “You really needed about a week — and the entire week was fully hands-on work. It was time-consuming and the data was not that reliable. We decided to figure out our own ways to improve the system.”
Through customer discovery interviews, Shu found that Qian’s lab wasn’t alone. She identified a need in academia and industry for more robust ribosomal profiling tools.
Driven by this demand, Shu and Qian worked together to develop Qez-seq, a technology that completes analysis of a ribosomal profile in just six hours (shortening the processing time by about 75%), at greater accuracy and with smaller samples than ever before.
“The existing technology was time-consuming and of low resolution,” says Qian. “It also required special equipment. By developing Qez-seq, we are hoping to allow scientists to obtain high-resolution map of ribosome positions on mRNA from small samples.”
Now, thanks to new funding, EzraBio, Inc. is expanding.
Shu is among seven UW–Madison innovators to receive funding from the university’s Discovery to Product (D2P) State Economic Engagement and Development (SEED) program. The SEED program supports growth of technology-based startup companies, evaluating projects on their innovation and potential benefits to Wisconsin’s economy. Funding through the D2P SEED program is matched by support from the Wisconsin Economic Development Corporation (WEDC).
“This grant is special because of its focus on the Wisconsin economy,” says Shu. “Applying for this grant meant thinking about forming partnerships and collaborations. I’m thinking about how to support local clients and how to get our supplies from local suppliers.”
“There are many collaborative projects ongoing,” adds Qian, who notes that the new, higher resolution technology is already paving the way for novel scientific findings. “We have discovered start codon-associated ribosome frameshifting during mRNA translation.”
Shu and Qian see in EzraBio, Inc. the potential to progress the field of protein synthesis analysis and support the development of future therapeutic treatments. “We think this technology will be helpful for scientists in industry and in academia who want to better understand protein synthesis and how it is regulated,” says Shu.
Shu also plans to establish career-building employment opportunities for recent college graduates. Shu, who teaches an introductory course for first-year biochemistry students and a capstone course for senior undergraduates, witnesses firsthand UW–Madison students’ progress during their time at the university. She says that EzraBio, Inc. can supplement local employment opportunities for biochemistry majors and keep knowledge and skills in the state of Wisconsin.
“I work with students at the university, and I hope I will be able to hire people who just graduated. I’d like to hopefully assist students with opportunities that will help them later in their career,” Shu says. “With this grant, we’ll first be hiring for a research intern position.”
Shu hopes that, as Madison’s role as a growing hub for biotechnology continues to grow, so will EzraBio, Inc., making their ribosomal profiling technology readily available to researchers around the country.
Written by Renata Solan. Photos: Paul Escalante/Biochemistry.