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New Biotech Process Fast-tracks Protein Therapy Research

A research team recently developed a new biotech technique that can accelerate research on protein therapies. These therapies have the potential to develop innovative drugs.

The masterminds behind the technique are Milan Mrksich, Michael Jewett, and Matt DeLisa.

Mrksich is a professor of biomedical engineering, chemistry, and cellular and molecular biology at Northwestern University’s McCormick School of Engineering and Applied Science. Jewett is an associate professor of chemical and biological engineering at the same university. Mrksich and Jewett also lead Northwestern University’s Center for Synthetic Biology.

DeLisa is a professor of engineering at the Robert Fredrick Smith School of Chemical and Biomolecular Engineering at Cornell University.

The researchers combined mass spectrometry with glycosylation. Mass spectrometry is Mrksich’s field of research. Jewett and Delisa specialize in glycosylation.

Glycosylation is the attachment of sugars to proteins. It plays a critical role in how proteins form and work in cells. It also defines how cells interact with other cells.

On the other hand, mass spectrometry accurately measures the mass of different molecules in a sample. Large biomolecules like proteins are identifiable by mass, which means that biologists can perform experiments using mass spectroscopy.

The three researchers developed a new platform that can characterize and optimize sequences to make glycoproteins using cell-free protein synthesis and mass spectrometry.

The new technique promises to decrease the time needed to test compounds for potential new drugs.

Currently, the cycle time to test each enzyme-substrate interaction can take weeks or months, explained Mrksich.

“We have radically accelerated the process,” Mrksich said. “Where researchers today can evaluate a couple of hundred potential glycosylation tags in a given period, we’ve brought together two high-throughput technologies that allow us to evaluate several thousand in that same time frame.”

The team combined three techniques from Northwestern laboratories:

  • Cell-free protein synthesis – a method of producing proteins without using living, intact organisms
  • Protein glycosylation – a process that allows researchers to rapidly create and test a large number of enzymes in test tubes
  • Self-assembled monolayers for matrix-assisted desorption/ionization (SAMDI) – a fast, low-cost, and label-free method of measuring biochemical activities on a surface

The team called the process GlycoSCORES, which stands for glycosylation sequence characterization and optimization by rapid expression and screening.

The work was supported by grants from the Defense Threat Reduction Agency and the National Science Foundation.

 

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