Protein Catalytic Capture
James R. Heath, Ph.D., professor of chemistry at California Institute of Technology, is working to advance the understanding of the tumor microenvironment of glioblastoma multiforme cancers.
“Many of the hallmarks of cancer, such as angiogenesis and metastasis, are thought to arise out of a process in which the immune system actually reinforces the aberrant nature of cancer.” As part of that overarching goal, Dr. Heath’s lab is developing a protein measurement instrument that operates at the single-cell level to help unravel the relationship between tumors and the immune system.
“We’re on the cusp of a $1,000 genome, and mRNAs have gotten significantly cheaper, but protein measurement hasn’t,” Dr. Heath said. “We’re trying to develop technology and approaches to do many measurements” simultaneously, at the same cost as a single measurement today.
The goal is to assay a patient’s blood at least daily against a panel of 30 to 50 proteins. Yet, “you can’t ask for blood every few hours,” and lab results typically come back one or two days later, limiting their usefulness in a real-time therapeutic environment. The technology, therefore, must be simple, automated, and require “only a pinprick of blood,” Dr. Heath said. Ideally, results would emerge within one hour.
The miniaturization process is completed. Now Dr. Heath and team are working with immunologists to overcome the limitations of existing assays. The challenge is that the antibodies used in assays all have slight variations among batches, which require instruments to be recalibrated with every change, which requires new proteins that must also be validated. This creates what amounts to a recalibration loop.
To break free of that loop, Dr. Heath is developing assays based upon protein catalyzed capturations, which he described as creating a catalytic scaffold. Essentially, he is creating a peptide library, identifying the binding loads. “Then we take a second group and modify it to have a complementary group.” The result is a catalytic scaffold that catalyzes the covalent coupling between the two groups, an approach that Dr. Heath insists is “very effective.”