Nikolai Slavov

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

Contact

Social Media

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

  • 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

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.

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

College Research Initiatives

Selected Publications

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 […]

graph

Faculty

Mar 29, 2021

Nature Biotechnology Perspective on Increasing proteomics throughput

BioE Assistant Professor and Allen Distinguished Investigator Nikolai Slavov published a perspective article in Nature Biotechnology “Increasing proteomics throughput” highlighting new mass-spectrometry technologies transcending limitations in the throughput of proteomics and opening the stage for many exciting applications.

Nikolai Slavov

In the Media

Mar 16, 2021

Voices of biotech research

As part of the 25th anniversary of Nature Biotechnology, BioE Assistant Professor and Allen Distinguished Investigator Nikolai Slavov published his future vision in the article “Voices of biotech research” about what he thinks are the most exciting and essential biotechnology opportunities.

professor working in lab

Faculty

Oct 08, 2020

Slavov Named Paul G. Allen Distinguished Investigator for Pioneering Single Cell Proteomics Research

Bioengineering Assistant Professor Nikolai Slavov was recently named a prestigious Allen Distinguished Investigator and was awarded a $1.5 million three-year grant to further his novel research on single cell proteomics. The Paul G. Allen Frontiers Group supports early-stage research with the potential to reinvent entire fields. Slavov is the first from Northeastern to receive the award.

Nikolai Slavov

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.

View All Related News