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Paul Blainey

Paul Blainey

· Professor

Massachusetts Institute of Technology · Biological Engineering

Active 2001–2024

h-index69
Citations15.2k
Papers271117 last 5y
Funding$22.9M
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About

Professor Paul Blainey is a faculty member of the Department of Biological Engineering at MIT. His research group focuses on addressing major challenges in single cell genomic and functional analysis, drug screening, and genomic screening by integrating diverse molecular, optical, and microfluidic technologies. The Blainey lab emphasizes quantitative single-cell and single-molecule approaches, aiming to enable multiparametric studies that reveal the workings of natural and engineered biological systems across various scales. Professor Blainey completed his undergraduate degrees in Mathematics and Chemistry at the University of Washington and earned a Master of Arts in Chemistry from Harvard University. He continued his doctoral studies in Physical Chemistry at Harvard University under the joint supervision of Professors Xiaoliang Sunney Xie and Gregory L. Verdine. His postdoctoral work was conducted at Stanford University, where he developed high-throughput microoptofluidic methods for whole-genome amplification of DNA from individual, uncultivated microbial cells in Professor Stephen Quake’s laboratory. He joined MIT as an Assistant Professor of Biological Engineering in 2012. His research integrates new microfluidic, optical, and molecular tools for application in biology and medicine, with an emphasis on multiparametric, single-cell, and single-molecule studies to understand biological systems.

Research topics

  • Biology
  • Computer Science
  • Computational biology
  • Medicine
  • Genetics
  • Microbiology
  • Nanotechnology
  • Theoretical computer science
  • Pathology
  • Telecommunications
  • Immunology
  • Virology
  • Bioinformatics
  • Materials science
  • Operating system
  • Mathematics

Selected publications

  • Catalase activity deficiency sensitizes multidrug-resistant Mycobacterium tuberculosis to the ATP synthase inhibitor bedaquiline

    Nature Communications · 2024 · 17 citations

    • Microbiology
    • Biology
    • Medicine

    Multidrug-resistant tuberculosis (MDR-TB), defined as resistance to the first-line drugs isoniazid and rifampin, is a growing source of global mortality and threatens global control of tuberculosis disease. The diarylquinoline bedaquiline has recently emerged as a highly efficacious drug against MDR-TB and kills Mycobacterium tuberculosis by inhibiting mycobacterial ATP synthase. However, the mechanisms underlying bedaquiline's efficacy against MDR-TB remain unknown. Here we investigate bedaquiline hyper-susceptibility in drug-resistant Mycobacterium tuberculosis using systems biology approaches. We discovered that MDR clinical isolates are commonly sensitized to bedaquiline. This hypersensitization is caused by several physiological changes induced by deficient catalase activity. These include enhanced accumulation of reactive oxygen species, increased susceptibility to DNA damage, induction of sensitizing transcriptional programs, and metabolic repression of several biosynthetic pathways. In this work we demonstrate how resistance-associated changes in bacterial physiology can mechanistically induce collateral antimicrobial drug sensitivity and reveal druggable vulnerabilities in antimicrobial resistant pathogens.

  • Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and identification of SARS-CoV-2 variants

    Nature Medicine · 2022 · 294 citations

    • Virology
    • Computational biology
    • Biology

    The coronavirus disease 2019 (COVID-19) pandemic has demonstrated a clear need for high-throughput, multiplexed and sensitive assays for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory viruses and their emerging variants. Here, we present a cost-effective virus and variant detection platform, called microfluidic Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (mCARMEN), which combines CRISPR-based diagnostics and microfluidics with a streamlined workflow for clinical use. We developed the mCARMEN respiratory virus panel to test for up to 21 viruses, including SARS-CoV-2, other coronaviruses and both influenza strains, and demonstrated its diagnostic-grade performance on 525 patient specimens in an academic setting and 166 specimens in a clinical setting. We further developed an mCARMEN panel to enable the identification of 6 SARS-CoV-2 variant lineages, including Delta and Omicron, and evaluated it on 2,088 patient specimens with near-perfect concordance to sequencing-based variant classification. Lastly, we implemented a combined Cas13 and Cas12 approach that enables quantitative measurement of SARS-CoV-2 and influenza A viral copies in samples. The mCARMEN platform enables high-throughput surveillance of multiple viruses and variants simultaneously, enabling rapid detection of SARS-CoV-2 variants.

  • Random access DNA memory using Boolean search in an archival file storage system

    Nature Materials · 2021 · 140 citations

    • Computer Science
    • Computer Science
    • Theoretical computer science
  • Massively multiplexed nucleic acid detection with Cas13

    Nature · 2020 · 789 citations

    • Computer Science
    • Computational biology
    • Computer Science

    .

  • An immune-cell signature of bacterial sepsis

    Nature Medicine · 2020 · 494 citations

    • Computational biology
    • Immunology
    • Medicine

Recent grants

Frequent coauthors

  • Nir Hacohen

    Broad Institute

    122 shared
  • Stephen R. Quake

    Stanford University

    65 shared
  • Pardis C. Sabeti

    61 shared
  • Deborah T. Hung

    Broad Institute

    54 shared
  • Miguel Reyes

    47 shared
  • Georgia Lagoudas

    Massachusetts Institute of Technology

    41 shared
  • Roby P. Bhattacharyya

    Harvard University

    39 shared
  • Rebecca J. Carlson

    Massachusetts Institute of Technology

    39 shared

Education

  • Ph.D., Biology

    Massachusetts Institute of Technology

    2006
  • B.S., Chemistry

    Harvard University

    2001

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