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This week we profile a recent publication in Nature Biotechnology from Jason Derks and a team in the lab of Dr. Nikolai Slavov at Northeastern University.

Jason Derks
Jason Derks
Nikolai Slavov
Nikolai Slavov

Can you provide a brief overview of your lab’s current research focus?

We aim to understand the rules governing emergent systems-level behavior and to use these rules to rationally engineer biological systems. We are specifically focussed on understanding post-transcriptional regulation in the immune system and during early development. To this end, we develop and apply methods for single-cell protein analysis by mass-spectrometry.

 

What is the significance of the findings in this publication?

Many biomedical questions demand scalable, deep, and accurate proteome analysis of small samples, including single cells. A scalable framework of multiplexed data-independent acquisition for mass spectrometry enables time saving by parallel analysis of both peptide ions and protein samples, thereby realizing multiplicative gains in throughput.

What are the next steps for this research?

plexDIA provides a proof of principle for a general approach that can be scaled by using higher plex non-isobaric mass tags that are optimized for DIA analysis. Such tags should be much easier and cheaper to design and manufacture than isobaric tags. Thus, we expect these tags to substantially increase the throughput and accessibility of sensitive protein analysis. Extrapolation of our 3-plexDIA results to a 100-plexDIA predicts the feasibility of analysing the proteomes of about 5,000 cells per day using a single MS instrument. Another avenue of plexDIA is increasing the throughput of applications seeking to quantify protein interactions, conformations and activities. For example, plexDIA is readily compatible with the recently reported covalent protein painting that enables analysis of protein conformations in living cells. Because there are no fundamental limitations preventing the creation of non-isobaric labels that would allow a higher degree of multiplexing with DIA, we expect plexDIA to enable even higher throughput in the future.

If you’d like us to mention your funding sources, please list them.

The research was funded by a New Innovator Award from the National Institute of General Medical Sciences from the National Institutes of Health under award DP2GM123497, an Allen Distinguished Investigator award through the Paul G. Allen Frontiers Group and a Seed Networks Award from CZI CZF2019-002424.

 

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