Functional protein measurement technology can accelerate drug discovery

A new biomedical research tool that allows scientists to measure hundreds of functional proteins in a single cell may offer new insights into cellular machines. Led by Jun Wang, an associate professor of biomedical engineering at Stony Brook University, this microchip analysis – called single-cell cyclic multiplex technology in situ (CycMIST) – could help advance advances in areas such as molecular diagnostics and drug discovery. Details of the cyclic microchip analysis method are published in Nature Communications.

While newer single-cell omics technologies (ie, genomics, transcriptomics, etc.) have revolutionized the study of complex biological and cellular systems, and scientists can analyze the genomic sequences of individual cells, these technologies do not apply to proteins because are not amplified as DNA. Thus, protein analysis in single cells did not lead to large-scale experiments. Because proteins are cellular functions and biomarkers for cell types and disease diagnosis, additional single-cell analysis is needed.

“The CycMIST test allows for an overall assessment of cell function and physiological status by examining 100 times more protein types than conventional immunofluorescent staining, a feature unmatched by any other similar technology,” explains Liwei Young, lead author of the study. and a postdoctoral fellow in the research team of Wang and Multiplex Biotechnology Laboratory.

The authors of the study Liwei Yang, left and Jun Wang, in the Wang laboratory next to the microscope, which includes the technology for single-cell cyclic multiplex in situ (CycMIST) to analyze proteins in individual cells.

Wang, who is affiliated with the Renaissance School of Medicine and the Stony Brook Cancer Center, and colleagues demonstrated CycMIST by detecting 182 proteins that include surface markers, neuronal function proteins, neurodegeneration markers, signaling pathway proteins, and transcription factors. They used a model of Alzheimer’s disease (AD) in mice to validate the technology and method.

By analyzing 182 proteins with CycMIST, they were able to perform a functional protein assay that revealed the deep heterogeneity of brain cells, distinguished AD markers, and identified the mechanisms of AD pathogenesis.

With this detailed way of detecting proteins in the AD model, the team suggests that such a functional protein assay may be promising for new drug targets for AD for which there is still no effective treatment. And they provide a landscape of potential drug targets at the cellular level from the CycMIST protein assay.

The authors believe that CycMIST may also have huge potential for commercialization.

They say that before this model of testing with CycMIST, researchers were able to measure and know only one peak of protein species in a cell. But this new approach allows scientists to identify and know the actions of every aspect of the cell and therefore they can potentially identify whether the cell is in a disease state or not – the first step in a possible way to diagnose the disease by analyzing a single protein cell. And compared to standard approaches such as flow cytometry, their CycMIST approach can analyze 10 times the amount of protein at the single cell level.

The researchers also suggest that the analysis of the cyclic microchip is portable, inexpensive, and can be adapted to any existing fluorescence microscope, which are additional reasons for its marketability if it proves effective with subsequent experimentation.

Much of the research for this study was supported by the National Institute on Aging of the National Institutes of Health (grant № R21AG072076), other NIH grants, and a grant to support the Sloan Catering Memorial Cancer Center.

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