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The omics era is in large part defined by a shift from the old target-of-interest days to an unbiased, discovery-first mindset: from a few genes to the whole genome, from a couple of proteins to the whole proteome. Scientists know all too well that any experiment limited to previously known elements carries the risk of missing an important finding, a key biomarker, a critical component that explains a biological mechanism.

In spatial biology, the hypothesis-free approach has been embraced for transcriptomic studies, with sequencers and other tools capable of identifying all transcripts in a specific location. But for spatial proteomics, technology has been far more limited. Every spatial proteomics platform available today restricts scientists to looking for a small number of known targets. Only one is designed for unbiased exploration.

The Microscoop® platform from Syncell is a microscopy-guided protein isolation and purification tool that provides an unbiased, subcellular view of all proteins in a precise biological location. The sample prep tool is designed to be used upstream of any mass spectrometer. Its output is highly stable, dried-down protein that can be shipped to a core facility or other service provider for rapid mass spec analysis. Unlike other approaches —including spatial proteomic instruments, laser capture microdissection, or proximity labeling—the Microscoop platform delivers complete coverage of proteins at single-cell and even subcellular resolution. This allows scientists to study the organization of proteins across tissues and cells without being limited to known targets. The tool currently achieves a resolution of 350 nanometers, and ongoing development efforts aim to reduce that to sub-100 nanometers for an even more precise view of biology.

This hypothesis-free technique for pinpointing a specific location and then mapping the entire proteome has important implications for drug discovery, neurological studies, cell biology research, and much more.

In one recent example, scientists in Cristiana Lungu’s, PhD, laboratory at the University of Stuttgart used this approach to look at triple-negative breast cancer cells. They focused on a well-known complex involved in the epigenetic regulation of these cells. The complex is associated with metastasis and creates nuclear bodies, whose mechanisms were not understood. By deploying the Microscoop platform, they characterized the proteins in and around these minuscule nuclear bodies. The resulting list included previously known proteins as well as a several new ones.

In an article, scientists describe knocking down one of those unexpected proteins. Without it, the nuclear bodies no longer formed and the cells did not develop a metastatic phenotype. Knowing the identity of this novel protein could lead to entirely new avenues for the discovery and development of therapies and biomarker-based diagnostic tools.

Separately, scientists have deployed the Microscoop platform to resolve protein aggregates linked to several neurodegenerative diseases. These abnormal protein structures, smaller than single cells, are difficult to study with conventional tools. Previous studies for amyotrophic lateral sclerosis (ALS) have focused on a single protein, TDP-43. But with an unbiased view, Wilfried Rossoll, PhD, and his team in the Translational Neuroproteomics Laboratory at the Mayo Clinic are now building a database of proteins found in and around TDP-43 aggregates to help accelerate discovery for these devastating diseases.

Unbiased spatial proteomics is critical for characterizing basic biology, broadening drug discovery efforts, and informing translational research. Without a true discovery tool for spatial proteomics, too many important proteins and potential drug targets will continue to be missed and key breakthroughs will be delayed.

To learn more about the Microscoop platform, please visit www.syncell.com.