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Nikolai Slavov

Junior Professor,  Bioengineering
Affiliated Faculty,  Biology

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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

  • 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

Professional Affiliations

  • 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

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.

 

Single-cell proteomics by mass-spectrometry

Cellular heterogeneity is important to biological processes, including cancer and development. However, proteome heterogeneity is largely unexplored because of the limitations of existing methods for quantifying protein levels in single cells. To alleviate these limitations, our laboratory developed Single Cell ProtEomics by Mass Spectrometry (SCoPE-MS), and validated its ability to identify distinct human cancer cell types based on their proteomes. To further advance single-cell protein analysis, we developed SCoPE2.

SCoPE2 introduced automated and miniaturized sample preparation that substantially lowers cost and hands-on time. It uses data-driven analytics to optimize instrument parameters for sampling more ion copies per protein, thus supporting quantification with improved count statistics. Furthermore, SCoPE2 uses peptide identification enhanced by incorporating retention time information within a principled framework, DART-ID.

SCoPE2 enables scalable, robust and affordable quantification of about 1,000 proteins per single cell, and about 3,000 proteins across many cells. This coverage is achieved with 90 min of analysis time per SCoPE2 set (about 6 min / cell), which allowed us to analyze hundreds of cells on a single instrument in a couple of days. Importantly, SCoPE2 succeeded in delivering and quantifying hundreds of ion copies from most detected proteins. This observation strongly supports the feasibility of single-cell LC-MS/MS protein quantification without amplification.

Research Centers and Institutes

Center for single-cell proteomics

Department Research Areas

Selected Publications

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In the Media

Feb 12, 2020

The single cell proteomics revolution

An editorial in BioanalysisZone highlights research from the Slavov Lab that has led to the rapidly advancing field of single-cell protein analysis by mass-spec.

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Faculty

Jan 31, 2020

Unpicking the Proteome in Single Cells

BioE Assistant Professor Nikolai Slavov’s research into using single-cell mass-spectrometry methods for high-throughput analysis of proteins is featured in the Science article “Unpicking the proteome in single cells.”

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Faculty

Sep 30, 2019

Voices in methods development

As part of the 15th anniversary of Nature Methods, BioE Assistant Professor Nikolai Slavov was featured in the article “Voices in methods development” about what he thinks are the most exciting and essential methodological biology challenges that are poised to be tackled in the near future.

Faculty

Aug 14, 2019

A Dream of Single-Cell Proteomics

BioE Assistant Professor Nikolai Slavov Lab was highlighted in the Nature Methods article A Dream of Single-Cell Proteomics highlighting their research in single-cell proteomics.

Faculty

Jul 10, 2019

Improving Protein Measuring Technology

Bioengineering Assistant Professor Nikolai Slavov has developed a breakthrough method of identifying more than a thousand proteins per cell which could help map the functions of them throughout the body.

Faculty

Feb 01, 2019

Bajpayee and Slavov Receive Sanofi iAwards

BioE Assistant Professors Ambika Bajpayee and Nikolai Slavov were each recipients of a $125K Sanofi iAward, which were created to promote scientific breakthroughs by tapping into the world’s greatest minds through close collaboration with renowned academic institutions.

Faculty

Nov 09, 2018

NIH Highlights Slavov's Innovative Research

The NIH Director’s office highlighted game-changing research on “Pinpointing Plenty of Proteins – in a Single Cell” conducted by BioE Assistant Professor Nikolai Slavov and his team.

Faculty

Oct 22, 2018

A big breakthrough for regenerative medicine?

BioE Assistant Professor Nikolai Slavov has devised a method to identify more than a thousand proteins in an individual cell and estimate their abundance.

Alumni

Oct 17, 2018

Through the Looking Glass of Single Cell Proteomics

Research from BioE Assistant Professor Nikolai Slavov’s lab was featured in Technology Network’s article “Through the Looking Glass of Single Cell Proteomics“

Faculty

Aug 03, 2018

Pioneering single cell proteomics

The article “Transformative Opportunities for Single-Cell Proteomics”, which is research from BioE Assistant Professor Nikolai Slavov’s Laboratory, is featured on the cover of the Journal of Proteome Research.

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