A Billion-Piece Puzzle

Completing the human protein project would revolutionize understanding of health and disease

By Roger AndersonApril 15, 2019

The first whole human genome cost about $2.7 billion to sequence in 2003. Today, anyone with $1,000 can learn about the entirety of their DNA, while $99 can offer clues on a person’s health and ancestry. 

While the field of genetics has exploded, early detection of disease using protein markers has remained elusive. Global leaders like Northwestern’s Neil Kelleher are attempting to change that paradigm.

“Like the Genome Project at the turn of the century, developing a disruptively cheap protein sequence is the major measurement challenge of our day,” says Kelleher, molecular biosciences, chemistry, and director of Northwestern Proteomics. “Mapping the universe of protein molecules will allow researchers to further pursue biomedical research goals like ‘designer organs,’ personalized drugs, and truly precise and early detection of human disease.”

Proteomics is the large-scale study of proteins. Until the 2000’s, proteomics relied on breaking a protein into small pieces, analyzing it using mass spectrometry, and piecing the information back together to learn their look and function. Alternatively to that traditional, or “bottom-up” approach, Kelleher and Fred McLafferty at Cornell established the feasibility of the “top-down” strategy. Since then, Kelleher has been demonstrating the main advantage of top-down proteomics by providing complete information about the sequence and composition of human proteins in health and disease.

“Imagine trying to do a puzzle where you don’t have the picture on the box of what it’s supposed to be, and you’re missing over half the pieces, and there are pieces of other puzzles in the box too,” says Kelleher, a member of Northwestern's Chemistry of Life Processes Institute as well as the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “That’s bottom-up proteomics, and that’s what the world uses.”

By looking at whole proteins, Kelleher and his team understand “the picture on the box” and then make sure they have all the pieces. At April’s Science Café, he will discuss his research career and latest results. The event takes place on April 24 from 6:30 to 8 p.m. at the Firehouse Grill, 750 Chicago Ave. in Evanston. Northwestern’s Science Café is free to attend and open to the public.