For its recent Technology Feature, Nature selected six thought leaders from across the globe to share one technology or topic that promises to transform life-science research in the year ahead.
Included in the big six is Xiaowei Zhuang, David B. Arnold Jr. Professor of Science, Professor of Chemistry and Chemical Biology, Professor of Physics, and RNA sequencing pioneer.
Zhuang and her five international peers—George Church, Elaine Mardis, Ruedi Aebersold, Rebecca Calisi Rodríguez, and Vivienne Ming—discussed their respective topics, their genesis and potential.
Zhuang's selection, a global cell atlas, shares the stage with virus-resistant pigs, genetic mechanisms driving sexual behaviour, and a distributed Internet of Scientific Things.
Together, these technological seeds represent innovations in both methodology and treatment. Their true value is not in their immediate, albeit significant, ability to neutralize viruses, improve cancer vaccines, or bring artificial intelligence into our homes and research. Like Zhuang's searchable atlas of all human cells, these technologies promise exponential revolution, in human health, disease diagnosis and treatment, and data access.
The Internet of Things has transformed many aspects of our lives and is now, along with other breakout technologies, poised to transform life-science research. Credit: chombosan/Alamy
Mapping the transcriptome
Xiaowei Zhuang Director, Center for Advanced Imaging, Harvard University, Cambridge, Massachusetts.
A new global initiative to identify all cell types in the human body and map their spatial organization — the recently launched Human Cell Atlas (HCA) initiative — is a grand goal. A project of this scale will need many complementary technologies.
Single-cell RNA sequencing is a powerful way to identify different cell types and an important tool for creating the HCA, but it requires taking a tissue apart into individual cells and then isolating the RNA. What’s not preserved is the spatial context of cells in a tissue — how they are organized and interact.
We’d like a technology that can provide this spatial context by imaging the transcription profiles of cells in intact tissue. My lab is developing MERFISH, or multiplexed error-robust fluorescence in situ hybridization, an image-based, single-cell transcriptomics approach.
MERFISH uses error-robust barcodes to identify each different type of RNA in the cell, and combinatorial labelling and sequential imaging to detect these barcodes in a massively multiplexed manner (see ‘Transcriptome mapping’).
We’ve already demonstrated the ability to image 1,000 different messenger RNAs (mRNAs) in single cells. With further development, MERFISH has the potential to detect the whole transcriptome in cells in intact tissues.
This spatially resolved RNA-profiling data will give us a physical picture for the HCA — we can image individual cells, categorize them by their gene-expression profiles and map their spatial organization. It can be combined with data on the morphology and function of cells obtained by other imaging technologies to further enrich that picture.
At the moment, our picture of the cell atlas is mostly incomplete. If you don’t have a global picture, you just don’t know what you are missing — let alone how to design effective therapeutics to intervene in the case of disease.
See Nature's Full List of Technology to Watch in 2018
