Researchers identify production locations of thousands of proteins within whole tissue and individual cells
Breaking the barriers in disease research, scientists at MIT and the Broad Institute have developed a groundbreaking technique called RIBOmap. This innovative method allows them to pinpoint the exact locations of thousands of proteins being synthesized within an intact tissue or even individual cells.
Each colored dot in the RIBOmap readout represents one mRNA molecule being used to produce the corresponding protein, a process called translation. The method, described in the latest issue of Science, opens new avenues for scientists to uncover the intricacies of how translation is regulated in individual cell types and how that changes in disease.
In the new study, the team used RIBOmap to study the translation of more than 5,000 genes in mouse brain tissue and found significant differences between where mRNAs were made and where the corresponding proteins were being synthesized, suggesting that cells are regulating translation in ways that traditional transcriptomic methods cannot detect.
"RIBOmap offers a fresh perspective that can reveal spatial patterns in translation at a resolution that has never before been possible," says Xiao Wang, a core institute member and Merkin Institute Fellow at the Broad and an assistant professor of chemistry at MIT. "By focusing on individual cells within a tissue, we can start to discover how different cell types are regulating translation differently."
Using RIBOmap, scientists can delve deeper into their understanding of the molecular intricacies governing protein production within a cell. The technique builds upon the STARmap method developed by Wang and her team, which visualizes the spatial organization of mRNA molecules within intact tissue by employing molecular probes that bind to specific mRNA sequences. The RIBOmap probes, however, attach only to mRNA molecules that are actively being translated, providing valuable insights into which mRNAs are being translated into proteins at any given time and place.
In the future, RIBOmap may prove instrumental in various disease research fields, such as unraveling the complexities of tumor microenvironments, understanding neurodegenerative diseases, and investigating drug responses and resistance mechanisms at a cellular level. The team believes that the technique can easily be applied to a variety of tissues and even to isolated human tissues, making it a versatile tool for scholars seeking to examine the protein synthesis landscape in far more detail than ever before.
This work was supported by multiple grants and fellowships, including the Searle Scholars Program, the National Institutes of Health, and the Merkin Institute Fellowship.
Insights: RIBOmap is an advanced adaptation of ribosome profiling (Ribo-seq) that combines high-resolution protein synthesis data with spatial transcriptomics or single-cell omics, offering researchers the ability to visualize protein synthesis at cellular and even subcellular levels within complex tissues. The technique distinguishes between cells producing specific proteins, offering a significant improvement over traditional RNA-seq techniques that only quantify mRNA presence. By providing valuable insights into gene regulation and cell function, RIBOmap may have direct implications for understanding and treating various diseases.
- The advancement in health and wellness, as well as medical-conditions research, is fueled by techniques like RIBOmap, a groundbreaking method developed by scientists at MIT and the Broad Institute.
- RIBOmap, described in the latest issue of Science, allows researchers to pinpoint the exact locations of thousands of proteins being synthesized within an intact tissue or even individual cells.
- Xiao Wang, a professor of chemistry at MIT and Merkin Institute Fellow, advocates that RIBOmap offers a fresh perspective revealing spatial patterns in translation at an unprecedented resolution.
- With RIBOmap, science and technology scholars can delve deeper into their understanding of the molecular intricacies governing protein production within a cell, opening new avenues for disease research fields such as tumor microenvironments, neurodegenerative diseases, and drug responses.
- The versatility of RIBOmap lies in its ability to be applied to various tissues, including isolated human tissues, making it a valuable tool for the press, professors, fellows, and graduate students seeking to examine protein synthesis landscapes with unparalleled detail.
- Numerous grants and fellowships, including the Searle Scholars Program, the National Institutes of Health, and the Merkin Institute Fellowship, supported the development and application of this innovative technology in the field of science.
