Amy Weeks, assistant professor in the Department of Biochemistry, is a 2024 Ono Breakthrough Science Initiative Grant awardee. The grant, which will provide $900,000 over three years, is funded by the Ono Pharma Foundation and supports research in the field of chemical biology with the potential to transform human health. With the funds, Weeks will broaden our ability to harness the many functions of the protein ubiquitin.
“There are just so many functions of ubiquitin in nature,” says Weeks. “As chemists and biologists, we want to take advantage of all of that potential to target proteins in human disease.”
Weeks hopes that her research will open the doors for scientists to do just that.
Ubiquitin, as the name implies, is a protein found in all eukaryotes. It serves as a tag, where it acts as a signal to alter a target protein’s activity. Among other functions, ubiquitination helps to determine a protein’s location within a cell and tags proteins for degradation.
Most current ubiquitin research has focused on the relationship between ubiquitin and protein degradation, which has propelled the development of a class of molecules known as immunomodulatory imide drugs (IMiDs) that are used for cancer treatment.
Weeks is interested in engineering tools to that will allow researchers to exploit the other ways ubiquitin affects a protein’s fate. “The overarching goal of our project is to understand how to program the ubiquitin code beyond destruction,” Weeks says.
There are three classes of enzymes associated with ubiquitination: enzymes that activate ubiquitin (E1), enzymes that carry activated ubiquitin (E2), and enzymes that bind to both E2 and the target protein, bringing together ubiquitin and its target (E3). Past research has explored how protein activity is altered by different E3s. Weeks plans to take an upstream approach to her research. By engineering a new E1, Weeks and her team will follow the ubiquitination cascades for each linking enzyme to identify all of the possible outcomes for a target protein.
“Understanding enzyme mechanisms can help us develop tools to probe biological processes at a new depth,” says Weeks. “We use chemical biology approaches to get an integrated view of cellular signaling, so our work fits well with the Ono Initiative’s focus on chemical biology projects with the potential to transform human health. We’re excited and grateful to receive this support and to join the Ono Initiative community.”
Written by Renata Solan.