Nikolai Slavov

Associate Professor,  Bioengineering
Allen Distinguished Investigator,  Allen Frontiers Group
Director,  Single-Cell Proteomics Center
Affiliated Faculty,  Biology
Faculty Fellow ,  Barnett Institute

Contact

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Office

  • Mugar Life Sciences, Office 334

Research Focus

Single-cell proteomics, Ribosome-mediated translational regulation, quantitative systems biology, mass-spectrometry

About

Nikolai Slavov received his undergraduate education from the Massachusetts Institute of Technology (MIT) in 2004. He pursued doctoral research in the Botstein laboratory at Princeton University, aiming to understand how cells coordinate their growth, gene expression, and metabolism. He discovered a simple mechanism that can account for the growth-rate dependent transcriptional responses across a wide range of growth conditions and growth rates  (Slavov and Botstein, 2011Slavov et al., 2011). After defending his dissertation in 2010, Nikolai Slavov began a postdoctoral project in the van Oudenaarden laboratory at MIT, aiming to understand the Warburg effect, a hallmark of cancer cells characterized by the fermentation of glucose in the presence of enough oxygen to support respiration. This work demonstrated that aerobic glycolysis can reduce the energy demands associated with respiratory metabolism and stress survival and that, contrary to expectations and decades-long assumptions, exponential growth at a constant rate can represent not a single metabolic/physiological state but a continuum of changing states characterized by different metabolic fluxes (Slavov et al., 2014). Following a lead from these experiments, Nikolai Slavov obtained direct evidence for differential stoichiometry among core ribosomal proteins in unperturbed wild-type cells (Slavov et al., 2015). His findings support the existence of ribosomes with distinct protein composition and physiological function that represent an explored layer of regulating gene expression.  Most recently, the Slavov laboratory developed methods for high-throughput Single Cell ProtEomics by Mass Spectrometry (SCoPE-MS and SCoPE2) and used them to quantify proteome heterogeneity during cell differentiation.

Education

  • PhD (2010), Botstein Laboratory, Princeton University
  • BS (2004), Biology, Massachusetts Institute of Technology

Honors & Awards

  • 2022 College of Engineering Faculty Fellow
  • Allen Distinguished Investigator Award
  • NIH Director’s New Innovator Award
  • SPARC Award from the Broad Institute of MIT and Harvard
  • Princeton University Dean’s Award
  • IRCSET Postgraduate Research Fellowship
  • Finalist in the Young European Entrepreneur Competition
  • Princeton Graduate Fellowship
  • MIT Undergraduate Fellowship
  • Eureka Fellowship for Academic Excellence
  • Bronze Medal in the 31st International Chemistry Olympiad
  • National Diploma for Exceptional Achievements in Chemistry

Leadership Positions

Professional Affiliations

  • Single-Cell Proteomics Center 
  • Barnett Institute of Chemical and Biological Analysis
  • Broad Institute of MIT & Harvard
  • American Society for Mass Spectrometry (ASMS)
  • American Society for Cell Biology (ASCB)
  • Genetics Society of America (GSA)

Research Overview

Single-cell proteomics, Ribosome-mediated translational regulation, quantitative systems biology, mass-spectrometry

Single-cell proteomics by mass-spectrometry

Many biological processes stem from the coordinated interactions of molecularly and functionally diverse cells. However, this diversity is relatively unexplored at the proteome level because of the limitations of conventional affinity-based reagents for quantifying proteins in single cells. To alleviate these limitations, in 2017 our laboratory introduced Single Cell ProtEomics by Mass Spectrometry (SCoPE-MS). Since then, we developed more powerful and fully automated methods, including SCoPE2pSCoPE, and plexDIA.

Single-cell proteomics by Mass-spec (SCoPE-MS)

Taking advantage of ideas for advancing data acquisition and interpretation, we developed next generation methods that increase the sensitivity, data completeness and flexibility of single-cell protein analysis. These allow prioritization of thousands of proteins and highly parallel analysis of both single-cells and peptides. All of these methods can be implemented using accessible commercial equipment.

Single-cell proteomics by Mass-spec

Ribosome-mediated translational regulation

All living cells must coordinate their metabolism, growth, division, and differentiation with their gene expression. Gene expression is regulated at multiple layers, from histone modifications (histone code) through RNA processing to protein degradation. While most layers are extensively studied, the regulatory role of specialized ribosomes (ribosome code) is largely unexplored. Such specialization has been suggested by the differential transcription of ribosomal proteins (RPs) and by the observation that mutations of RPs have highly specific phenotypes; particular RP mutations can cause diseases, known as ribosomopathies, and affect selectively the synthesis of some proteins but not of others. This selectivity and the differential RP transcription raise the hypothesis that cells may build specialized ribosomes with different stoichiometries among RPs as a means of regulating protein synthesis.
While the existence of specialized ribosomes has been hypothesized for decades, experimental and analytical roadblocks (such as the need for accurate quantification of homologous proteins and their modifications) have limited the evidence to only a few examples, e.g., the phosphorylation of RP S6. We developed methods to clear these roadblocks and obtained direct evidence for differential stoichiometry among core RPs in unperturbed yeast and mammalian stem cells and its fitness phenotypes. We aim to characterize ribosome specialization and its coordination with gene regulation, metabolism, and cell growth and differentiation. We want to understand quantitatively, conceptually, and mechanistically this coordination with emphasis on direct precision measurements of metabolic fluxes, protein synthesis and degradation rates in absolute units, molecules per cell per hour.

 

Slavov Laboratory

We aim to understand the rules governing emergent systems-level behavior and to use these rules to rationally engineer biological systems. We make quantitative measurements, often at the single-cell level, to test different conceptual frameworks and discriminate among different classes of models.

Slavov Laboratory

Research Centers and Institutes

Selected Publications

In the Media

Sep 08, 2022

Sensitive protein analysis with plexDIA

Technology for sensitive protein analysis developed in the laboratory of BioE Associate Professor and Allen Distinguished Investigator Nikolai Slavov was highlighted in a Nature Methods article Sensitive protein analysis with plexDIA.

Faculty

Jul 15, 2022

Nature Biotechnology published a framework for multiplicative scaling of single-cell proteomics developed in the Slavov Laboratory

The laboratory of Allen Distinguished Investigator and BioE Associate Professor Nikolai Slavov published “Increasing the throughput of sensitive proteomics by plexDIA” in Nature Biotechnology.

Faculty

Apr 15, 2022

Faculty and Staff Awards 2022

Congratulations to all the winners of the faculty and staff awards, and to everyone for their hard work and dedication during the 2021-2022 academic school year.

Faculty

Dec 23, 2021

COE Professors Selected in Stanford University List of Top 2% Scientists Worldwide

The following COE professors are among the top scientists worldwide selected by Stanford University representing the top 2 percent of the most-cited scientists with single-year impact in various disciplines. The selection is based on the top 100,000 by c-score (with and without self-citations) or a percentile rank of 2% or above. The list below includes […]

Faculty

Nov 02, 2021

Research from the Slavov Laboratory published in Nature Protocols

Research from the laboratory of BioE Associate Professor and Allen Distinguished Investigator Nikolai Slavov has been published as “Multiplexed single-cell proteomics using SCoPE2” in Nature Protocols.  

Faculty

Nov 02, 2021

Slavov Research Featured on Cover of C&EN

BioE Associate Professor and Allen Distinguished Investigator Nikolai Slavov’s research on “Individual cells’ proteins vary. Single-cell proteomics can now show how” was featured on the cover of the C&EN journal. In Brief Measurements of cell mixtures can hide differences between cells that might be important in biology or disease studies. Researchers have long had tools […]

Nikolai Slavov

Faculty

Sep 28, 2021

Identifying Novel Markers of Senescence Cells

BioE Associate Professor Nikolai Slavov, in collaboration with Massachusetts General Hospital, was awarded a $588K NIH grant from the National Cancer Institute for “Single-Cell Proteomic Identification of Novel Markers of Senescence.”

Illustration of the two paths to the proteome.

Faculty

Sep 21, 2021

Single-cell Proteomics takes Centre Stage

BioE Associate Professor and Allen Distinguished Investigator Nikolai Slavov was featured in the Nature technology feature “Single-cell proteomics takes centre stage” which highlights single-cell proteomics technology developed by the Slavov Laboratory.

In the Media

Aug 05, 2021

Towards resolving proteomes in single cells

BioE Associate Professor Nikolai Slavovo was featured in the Nature Methods article “Towards resolving proteomes in single cells” which highlights single-cell proteomics methods (SCoPE-MS and SCoPE2) developed by the Slavov Laboratory, and their application to characterising the emergence of molecular diversity in a type of innate immune cells, macrophages.

abstract photo of women doctor pointing to tablet with medical imagery around it

Faculty

May 11, 2021

Just What the Doctor Ordered

Human beings are some of the most complex systems in the world, and responses to illness, disease, and impairments manifest in countless different ways. When it comes to making sure that your system stays up and running, healthcare professionals typically have their own deep well of knowledge—but the addition of artificial intelligence tools offers unprecedented […]

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