Setting audacious goals for technology innovation is a critical component of the Human Proteoform Project, a $1.3 billion movement to weigh and characterize every protein variation, (called proteoforms) in the human body.  A new technology announced today, co-developed by Northwestern’s Neil Kelleher, director of Northwestern Proteomics and Chemistry of Life Processes Institute, is expected to bring scientists closer to achieving this bold mission within the next decade.

“The new Thermo Scientific Direct Mass Technology mode dissolves the complexity barriers inherent to other approaches and enables a wealth of investigations that were once firmly out of reach,” says Iain Mylchreest, vice president, research and development, analytical instruments, Thermo Fisher Scientific, a global manufacturer of scientific instruments, equipment, and software.

Proteins form the building blocks of all the cells in our body and steer their behavior. When something goes wrong with human health, such as cancer or heart disease, proteins are typically involved and yet less than .05 percent of the body’s estimated 1 billion proteoforms have been identified and measured.

One of the leading voices in the bold initiative to sequence the entire human proteome is Kelleher, a world-leading expert in top-down proteomics, a method for analyzing proteoforms in their entirety.  The top-down method provides the most comprehensive and precise measurement of proteins available today.

For decades, Kelleher and his team have partnered closely with Thermo Fisher Scientific to provide testing and input to crack the code on human proteoforms. The Direct Mass Technology mode, the company’s most powerful instrument to date, allows scientists to visualize proteoforms to unprecedented length scales.

“Partnering with leading researchers is a critical component of developing new breakthrough technologies and our long-standing collaboration with Professor Neil Kelleher and his group has really propelled the development of Direct Mass Technology mode,” says-Mike Senko, principal scientist, Thermo Fisher Scientific. “Our co-development activities have helped shape the technology to make sure it delivers the essential functionality to continue pushing the boundaries of science.”

That’s good news for the 400 scientists who have joined the Consortium for Top-Down Proteomics (CTDP), an organization co-founded by Kelleher, that is working to drive innovation and understanding of the critical role proteoforms play in human biology.  The CTDP also seeks federal funding and support for the Human Proteoform Project from a growing list of industry members and academic institutions.

A key product of the initiative is the Human Proteoform Atlas, a worldwide online repository of experimentally verified human proteoforms developed by Northwestern Proteomics. The resource maps known proteoforms and their corresponding cell and tissue types for the benefit of developers of new diagnostics and novel therapies for disease.

Thermo Fisher’s new mass spectrometry technology is expected to be a game-changer enabling faster and more precise proteoform discovery.

“Up until this point, we have been challenged when protein complexes get large or get very complicated and it was unintelligible. You couldn’t assign masses. You couldn’t go forward with your work,” says Kelleher. “The new technology from Thermo Fisher allows us now to push right through that barrier.”

Learn more and watch the video.

by Lisa La Vallee