McShan, an assistant professor in the School of Chemistry and Biochemistry, has been awarded a $1.4 million CAREER grant from the National Science Foundation (NSF) to support this research.

“Protein-lipid assemblies carry out all sorts of biological functions, and harnessing their interactions could lead to powerful tools and treatments — but historically, they’ve been difficult to study,” McShan says. “Building resources for researchers and making this information accessible are critical steps in developing this field. This CAREER grant will enable me to expand the current knowledge base, while also allowing me to develop a class that will train the next generation of researchers, which is hugely important to me.”

The NSF Faculty Early Career Development Program is a five-year grant designed to help promising researchers establish a foundation for a lifetime of leadership in their field. Known as CAREER awards, the grants are NSF’s most prestigious funding for early-career faculty.

Expanding access

Crucial for nearly all biological processes, lipid-protein interactions play a key role in everything from immune responses to energy storage — but what drives their interactions has historically been difficult to map and understand.

McShan will use the CAREER grant to expand that knowledge base, experimenting in the lab to characterize protein-lipid interactions, and developing computational tools that can predict those interactions. The work will include an in-depth study of how lipids interact with different families of proteins that are important for immune system function.

“Right now, understanding protein-lipid assemblies is expensive in both time and lab materials,” McShan says. “My goal is to create computer models that can predict how these biomolecular interactions occur, what they look like, and how they contribute to cellular functions.”

The new model would allow researchers to quickly and inexpensively ‘experiment’ with molecules on a computer, vastly expanding the amount of research that could be conducted. 

The project builds on McShan’s recent publication in the Nature-family journal Communications Chemistry, which showcased BioDolphin — a first-of-its-kind, comprehensive, and annotated database of protein-lipid interactions that are all integrated into a user-friendly web server and freely accessible to all. 

It’s also adjacent to research funded by a Curci Grant from the Shurl and Kay Curci Foundation, which McShan was previously awarded for research on cutting-edge cancer treatments that involved identifying new cancer lipid signatures in tumor cells, and characterizing known cancer lipid antigens.

Pioneering the future of research

Additionally, the CAREER grant will support McShan’s initiatives to train the next generation of researchers through a new class centered around hands-on laboratory research and peer mentorship. Students will have the opportunity to pick a protein-lipid assembly, study it using computational and experimental biophysical methods, develop testable hypotheses, and — if successful — publish their results in peer reviewed journals.

The class will also pair undergraduate and graduate students into research teams. “I’m excited to see how a peer mentoring approach will add depth to the class,” McShan shares, explaining that graduate students will gain valuable mentoring experience in a collaborative research environment. “This is very different from typical mentoring experiences many graduate students have, which tend to be more along the lines of a TA experience rather than collaborating on hands-on research.”

“This type of class, to my knowledge, hasn’t been offered before, and there’s a lot of research that I’m doing to lay the groundwork for it,” McShan adds. “Hopefully, it can not only introduce students to lipid-based research — something typically lacking in many biochemistry curricula — but also to the type of collaborative mentorship we want to foster in research.”