Juan Guan, Ph.D., an assistant professor in the department of physics in the University of Florida College of Arts and Sciences, has been awarded a $1.9 million grant from the National Institute of General Medical Sciences to explore the mechanisms behind the assembly and regulation of non-canonical biomolecular condensates.
These condensates are tiny membrane-less structures that self-assemble in living cells. They are found in a range of cell types and can exist as protein-only structure or with nucleic acids attached.
“These tiny molecules play an important role in normal cell processes,” said Guan, a member of the Cancer Center’s Mechanisms of Oncogenesis research program. “If they assemble incorrectly within cells, they can cause a variety of problems, including cancer. Our research looks to understand why they assemble incorrectly so we can prevent this.”
Previous research from the Guan lab found that the protein EML4-ALK can form condensates in the cytoplasm without traditionally recognized protein domains, which are distinct regions within a protein that are responsible for a specific function. This suggests that this protein has a unique way of creating condensates that is not well understood.
Through their newly funded project, Guan and her team hope to accomplish two goals. First, the team hopes to identify more of these alternative protein assembly structures. Second, the group hopes to uncover the physical principles that regulate composition and dynamics in multi-protein condensates.
An increased understanding of the function and malfunction of biomolecular condensates will help increase researchers’ ability to regulate biomolecular condensate assembly and functions. This work could lead to new opportunities to control cellular processes through independent physical approaches, offering a new framework to prevent, diagnose and treat condensate-driven diseases, including cancer.
“Because these assembly mechanisms can also be disease mechanisms like condensates-mediated aberrant cell signaling, it is important that we identify and characterize the non-canonical motifs in order to find novel molecular targets and therapeutic opportunities,” Guan said.