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A scientist at work in Whitehead Institute's Proteomics Innovation Center

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Mackenzie White/Whitehead Institute

Whitehead Institute Innovation Centers receive Mass Life Sciences Center grants

Whitehead Institute has received three grants from the Massachusetts Life Sciences Center (MLSC) to add advanced instruments to its Innovation Centers, strengthening shared resources that help scientists sort rare cells, image molecules inside cells, and measure and map the physical connections among proteins.

The awards will support new equipment in flow cytometry, microscopy, and quantitative proteomics—three areas in which expert staff help Whitehead researchers and outside academic and industry scientists apply specialized technologies to complex biological questions. By placing these tools in shared, expert-run facilities, the grants will help many researchers ask questions about our biology that might otherwise have been impossible to ask, and devise experiments to find answers that could one day lead to scientific and medical advances.

The grants include $500,000 toward a spectral cell sorter for the Flow Cytometry Innovation Center, led by Patrick Autissier; $500,000 toward a single-molecule localization super-resolution microscope for the W.M. Keck Microscopy Innovation Center, led by Cassandra Rogers; and nearly $2.26 million toward a mass spectrometer for the Quantitative Proteomics Innovation Center, led by Fabian Schulte. Whitehead Institute will contribute additional support for each project, including $233,000 for the cell sorter, $65,000 for the microscope, and $1.875 million for the proteomics facility and renovation costs.

The Innovation Centers extend what individual labs can do on their own. Many experiments in modern biology depend on instruments that are expensive to purchase and technically demanding to operate. The centers pair those instruments with expert staff who help researchers refine experimental design, prepare difficult samples, troubleshoot problems, and analyze complex data.

For the Flow Cytometry Innovation Center, the grant will expand researchers’ ability to distinguish and isolate specific cells from complex samples. The new system can detect even subtle differences between cells and measure many features at once. These capabilities will support research in cancer, immunology, infectious disease, cell engineering, metabolism, and other fields that depend on isolating specific cells for further study.

Demand for the Flow Cytometry Innovation Center has grown among Whitehead researchers and external users, including biotech companies that rely on the core for staff-supported cell sorting. 

“This grant is fantastic for us because it allows us not only to replace an old instrument, but to replace it with a brand-new technology,” Autissier said. “It’s going to open a lot more opportunity to have this kind of instrument on site.”

“[This award] makes new science happen that otherwise would not be possible,” Schulte said.

The new microscope for the Microscopy Innovation Center will enable researchers to visualize cellular structures and molecular dynamics that are too small or too fast for conventional light microscopes to capture. The system can resolve individual molecules with extremely high precision and track their movement in living cells, giving researchers a closer view of how cells organize their internal machinery. It will help researchers ask questions about how cells grow and change over time, what changes inside cells during disease, and how potential therapies affect molecular behavior. 

The system will also become part of correlative light and electron microscopy workflows developed with the Nanotechnology for Integrative BioEM facility at the Koch Institute. Those workflows combine two views of the same sample: light microscopy to identify specific molecules or events, and electron microscopy to the surrounding architecture of the cell.

“The acquisition of the Abbelight Single Molecule Localization/TIRF system closes a previous technology gap in our technology portfolio.  We’re also excited to continue our collaboration with the Integrative BioEM core and with Abbelight,” Rogers said.

The grant to the Quantitative Proteomics Innovation Center will support a new platform for protein crosslinking mass spectrometry, or XL-MS, a method for studying how proteins connect. Proteomics uses mass spectrometry to identify and measure proteins, the molecules that perform much of the work inside cells. XL-MS adds another layer of information by helping researchers determine which proteins, or which regions of proteins, are close together in a biological sample.

Those relationships can be hard to capture. Schulte compares the challenge to studying a car after it has been taken apart. A standard proteomics experiment can identify many of the pieces, but it may lose information about how those pieces fit together. XL-MS helps preserve some of those relationships.

“One of the key problems when you study protein interactions is that very often, they’re transient,” Schulte said. “When you are isolating the proteins, the interactions are lost.”

The new instrument will help establish an open-access XL-MS platform in Massachusetts. Schulte said researchers who want to conduct these experiments often have to send samples elsewhere or find labs that can attempt the work without necessarily offering it as a standardized service.

“It makes new science happen that otherwise would not be possible,” Schulte said. “Protein crosslinking mass spectrometry is one of the most difficult applications in proteomics and no other facility on the East Coast offers it as a standardized service.”

The platform will also strengthen the connection between proteomics and structural biology. When paired with other approaches, XL-MS can help researchers build more accurate models of protein complexes involved in disease, drug response, and basic cellular function.

Whitehead Institute’s Innovation Centers have long been a key asset for the Institute, bringing together expert scientists and cutting-edge technologies to accelerate the path from question to discovery to application. These MLSC grants not only serve as recognition of the value of Whitehead’s Innovation Centers to biomedicine, but will also strengthen and expand the experimental options available to Whitehead researchers and the broader scientific community across academia and industry.

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