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Bernd Bodenmiller: Single-Cell Proteomics

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Recommended by: Ruedi Aebersold, Swiss Federal Institute of Technology Zurich

University of Zurich researcher Bernd Bodenmiller studies single-cell signaling with a technology almost as newly minted as his lab.

Bodenmiller launched his lab in February, and three months later, in May, he installed the instrument that has become key to his work — DVS Sciences' CyTOF mass cytometer, a new take on flow cytometry that lets scientists measure dozens of targets at once in single cells.

During his PhD work, Bodenmiller focused on the analysis of protein phosphorylation and cellular signaling. As he was wrapping up his thesis, though, he says he realized that "if you want to study signaling in disease, then you need the ability to study signaling on a single-cell level." This idea, he notes, led him to a postdoc position in Garry Nolan's lab at Stanford, which had just become among the first to obtain the new CyTOF machine.

The CyTOF uses metal-conjugated antibodies to tag cellular targets of interest, reading them out via time-of-flight mass spectrometry. While conventional flow cytometry can typically measure 10 to 20 targets at once, the CyTOF can multiplex up to 100 targets. Since taking the technique to his own lab, Bodenmiller has been using it to study processes underlying cancer metastasis, he says, adding that his team is currently focused on breast cancer.

Paper of note

In August, Bodenmiller, along with former Stanford colleagues including Nolan, published a paper in Nature Biotechnology using the CyTOF to analyze how various inhibitors modulate cellular signaling in immune cells. That paper, which Bodenmiller cites as perhaps his most important publication to date, also put forth a new technique for multiplexing on the instrument, "so we could very rapidly look at the effects of these inhibitors and do this under a very high number of conditions," he says.

Looking ahead

Moving forward, Bodenmiller says he hopes to continue method development work on the CyTOF. In particular, he notes, his lab is working on "methods for the CyTOF that allow us to measure cells in a native microenvironment, which is important for understanding many biological questions, especially in disease."

At the moment, the machine can only measure cells in suspension, meaning that researchers "lose any information about cell localization," he says.

Bodenmiller also aims to better integrate CyTOF with other types of research, such as single cell genomics and transcriptomics. "The information that we get from the CyTOF is very powerful, but there are many other levels of information as well, and I think we should find ways that we can combine and integrate this information," he says.

And the Nobel goes to…

Were there to be a Nobel Prize in his future, Bodenmiller says he'd like to win it either for developing "a new method or technology that becomes so commonplace and delivers such a quality of data that everybody is using it – like Sanger sequencing" or for elucidating "a new mechanism of how cells process information or communicate with each other."

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