Gels
Technology for single-cell analysis

Streamlining experimental science with new techniques for high-throughput single-cell analysis

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Droplets
Evolution and drug resistance

Studying combinatorial antibiotic strategies using optical and microfluidic technologies

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Scope
Protein-DNA biophysics

Applying single-molecule methods to study the activity of DNA binding proteins

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We're located at the Broad Institute in Cambridge, MA

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Molecular, optical, and microfluidic technology for probing and controlling cell function.
The Blainey laboratory integrates multiple technologies to robustly probe and manipulate cellular activities and actively disseminates new methods to researchers and scientists around the world. Our approaches typically integrate microfluidic, imaging, and/or molecular technologies.




OVERVIEW

The Blainey group innovates new microfluidic, optical, and molecular tools for application in biology and medicine. We emphasize high-throughput quantitative single-cell and single-molecule approaches, applying these tools and chemical, physical, and statistical modes of thinking to understand and control natural and engineered biological systems.



AREAS OF FOCUS

Droplets Integrated sample preparation for NGS assays

Scope Novel approaches to single-cell analysis

Scope One-dimensional biochemistry

Gels Evolution and drug resistance


Integrated sample preparation for NGS assays
Sample preparation is the new frontier in next-generation sequencing (NGS). We have developed a new family of multi-layer soft microfluidic devices that automate all the steps required to render biomass ready for NGS assays like whole-genome sequencing, transcriptome profiling, and epigenome profiling. In some applications, we further integrate upstream sample processing steps like purification of target cell types. Our devices benefit NGS workflows in several ways:

- reduced sample input requirement

- reduced hands-on time

- faster turn-around time

- improved reliability

- lower cost per sample

- improved sample throughput


Novel approaches to single-cell analysis

Single-cell analysis technology needs major advancement to serve many applications in the sciences and medicine. We integrate molecular and device-centric technologies to drive breakthroughs in medicine and the study of evolution.

- Single-cell functional genomics. We have developed a single-cell platform that enables pooled genetic screening for complex cellular phenotypes at lower cost.

- Hydrogel-based whole-genome amplification. We have developed a whole-genome polymerase colony (polony) method for en mass amplification and selective recovery of single-cell genomes that improves data quality and requires no specialized instrumentation.

- Complex sample processing in micro-droplets. We have developed a micro-droplet platform for massively scalable processing of single cells simultaneously for genomic analysis that integrates cell handling, amplification, and library construction.

- Live cell genomics. We look to reimagine NGS as a live-cell technique to generate time series data from single cells in situ. This contrasts with essentially all current applications of NGS, which require killing the cells under study prior to readout.


One-dimensional biochemistry

Natural proteins move dynamically along the genome by helical sliding to interact with each other and locate genomic targets in "one dimension" on DNA. We recently discovered that nuclear localization signal (NLS) peptides are sufficient for DNA binding and sliding activity in cells.

- We are exploring the biological implications of potentially widespread sliding activity in cells.

- We seek to understand the molecular mechanism of short peptide sliding.

- We work to engineer small molecules with sliding activity for biomedical applications.


Evolution and drug resistance

Cells constantly undergo mutation from chemical processes and replication errors. Many of these genomic alterations are reversed by DNA repair mechanisms, but others persist in the genome to drive evolution and give rise to some of society's greatest challenges such as cancer and pathogen antibiotic resistance. We aim to achieve a deep, quantitative, and unbiased understanding of mutational processes and use this knowledge as a basis for managing the consequences of cellular evolution in a biomedical context.

- We are developing a single-cell, single-generation resolved genomic approach for in vitro evolution studies. This method enables the analysis of mutations genome-wide with unprecedented accuracy and sensitivity to deleterious mutations.

- We have developed a new micro-droplet drug-screening platform that brings the scale necessary for combinatorial treatments designed to enhance the potency and life-span of antibiotics in the clinic.





Paul C. Blainey
Assistant Professor of Biological Engineering, MIT
Core Member, Broad Institute of Harvard and MIT
AM, PhD in Physical Chemistry - Harvard
BS, Chemistry and BA, Mathematics - University of Washington



LAB MEMBERS

Emily Botelho
Administrative Assistant
ebotelho'at'broadinstitute.org
Avtar Singh
Postdoctoral Associate
avsingh 'at'broadinstitute.org
Kianna Billman
Research Associate
kbillman'at'broadinstitute.org
Jacob Borrajo
Graduate Student
jborrajo'at'mit.edu
Yehuda Brody
Postdoctoral Associate
ybrody'at'broadinstitute.org
Atray Dixit
Coadvised Graduate Student
acdixit'at'broadinstitute.org

David Feldman
Graduate Student
feldman'at'broadinstitute.org

Anthony Garrity
Research Associate
agarrity'at'broadinstitute.org

Jared Kehe
Graduate Student
jkehe'at'broadinstitute.org
Soohong Kim
Postdoctoral Associate
soohong'at'broadinstitute.org
Ankur Kulshrehtha
Postdoctoral Associate
ankurk'at'broadinstitute.org
Tony Kulesa
Graduate Student
akulesa'at'mit.edu
Miguel Reyes
Graduate Student
msreyes'at'mit.edu
Luke Funk
Graduate Student
lukefunk'at'broadinstitute.org
Georgia Lagoudas
Graduate Student
lagoudas'at'mit.edu
Mohamad Najia
Graduate Student
mnajia'at'broadinstitute.org

Navpreet Ranu
Graduate Student
nranu'at"mit.edu
Andy Tu
Coadvised Graduate Student
andytu'at'mit.edu

Kan Xiong
Postdoctoral Associate
kanxiong'at'broadinstitute.org
Lily Xu
Graduate Student
xul'at'mit.edu



Alumni

Francis McCarthy
Juan Hurtado
Graduate Student, University of California Berkeley
Babak Babakinejad
Dwayne Vickers
Genomics Institute of the Novartis Research Foundation
Investigator II
Evangelos Gatzogiannis
Princeton University
Imaging Core Facility Director
Joachim DeJonghe

Robin Kirkpatrick
Graduate Student
University of Washington, Biological Physics, Structure and Design
Anja Mezger
Leanna Morinishi

Graduate Student, UCSF
Philipp Schramm



Undergraduate and High School Students

Francis Chen
Sarah Diiorio
Andrea Li
William Long
Annaliese Getz
Nathan Hunt
Daniel Murphy
Rebecca Noel
Ritish Patnaik
Uriel Sanchez
Daniel Sazer
Christian Richardson
Nathalie Rivas
Prianca Tawde
Anna Zukowski
Jaya Narain
Darian Bhatena
Jameson Kief
Allen Lee
Aman Patel
Nova Xu
Zachary Holbrook


SELECTED RECENT PUBLICATIONS

For complete and updated publication listings, please see: this PubMed link, this bioRxiv link, and this Google Scholar profile link.

Kulesa, A.; Kehe, J.; Hurtado, J.; Tawde, P.; Blainey, P.C. Combinatorial Drug Discovery in Nanoliter Droplets. bioRxiv (2017) 210492. bioRxiv 210492

Yu, F.; Blainey, P.C.; Schulz, F.; Woyke, T.; Horowitz, M.A.; Quake, S.R. Microfluidic-based mini-metagenomics enables discovery of novel microbial lineages from complex environmental samples. bioRxiv (2017) 114496. bioRxiv 114496

Guo, S-M.; Veneziano, R.; Gordonov, S.; Li, L.; Park, D.; Kulesa, A.B.; Blainey, P.C.; Cottrell, J.R.; Boyden, E.S.; Bathe, M. Multiplexed confocal and super-resolution fluorescence imaging of cytoskeletal and neuronal synapse proteins. bioRxiv (2017) 111625. bioRxiv 111625

Kim, S.; De Jonghe, J.; Kulesa, A.B.; Feldman, D.; Vatanen, T.; Bhattacharyya, R.; Berdy, B.; Nolan, J.; Gomez, J.; Epstein, S.; Blainey, P.C. High-throughput automated microfluidic sample preparation for accurate microbial genomics. Nat. Commun. (2017) 8, 13919.
- See research highlight at Nature Methods

Bennett, R.D.; Ysasi. A.B.; Wagner, W.L.; Valenzuela, C.D.; Tsuda, A.; Pyne, S.; Li, S.; Grimsby, J.; Pokharel, P.; Livak, K.J.; Ackermann, M.; Blainey, P.; Mentzer, S.J. Deformation-induced transitional myofibroblasts contribute to compensatory lung growth. Am. J. Physiol. Lung. Cell. Mol. Physiol. (2017) 312, 1, L79-L88.

Xiong, K.; Erwin, G.S.; Ansari, A.Z.; Blainey, P.C. Sliding on DNA: from peptides to small molecules. Angewandte Chemie Int. Ed. (2016) 55, 48, 15110-15114.

Xu, L.; Brito, I.L.; Alm, E.J.; Blainey, P.C. Virtual microfluidics for digital quantification and single cell sequencing. Nat. Methods (2016) 13, 759–762.

Brito I.L.; Yilmaz S.; Huang K.; Xu L.; Jupiter S.D.; Jenkins A.P.; Naisilisili W.; Tamminen M.; Smillie C.S.; Wortman J.R.; Birren B.W.; Xavier R.J.; Blainey P.C.; Singh A.K.; Gevers D.; Alm E.J. Mobile genes in the human microbiome are structured from global to individual scales. Nature (2016) 535, 7612, 435-9.

Xiong, K.; Blainey, P.C. Molecular sled sequences are common in mammalian proteins. Nucleic Acids Research (2016) 44, 5, 2266-2273.

Mangel, W.F.; McGrath, W.J.; Xiong, K.; Graziano, V.; Blainey, P.C. Molecular sled: an eleven-amino acid vehicle that facilitates biochemical interactions via sliding components along DNA. Nature Communications (2015), 7, 10202, 1-11.

Morinishi, L.M.; Blainey, P.C. Simple bulk readout of digital nucleic acid quantification assays. J. Vis. Exp. (2015), 103, e52925.

Kulesa, A.; Krzywinski, K.; Blainey, P.C.; Altman, N. Points of significance: sampling distributions and the bootstrap. Nature Methods (2015), 12, 477–78.

Bennett, R. A.; Ysasi, A.B.; Belle, J.M.; Wagner, W.; Konerding; M.A.; Blainey, P.C.; Pyne, S.; Mentzer, S.J. Laser microdissection of the alveolar duct for single-cell genomic analysis. Frontiers in Oncology (2014), 4, 260, 1-8.

Blainey, P.C.; Quake, S. Dissecting genomic diversity, one cell at a time. Nature Methods Commentary (2014), 11, 19–21.

Vestergaard, C.L.; Blainey, P.C.; Flyvbjerg, H. Optimal estimation of diffusion coefficients from single-particle trajectories. Physical Review E. Statistical, Nonlinear, and Soft Matter Physics (2014), 89, 2, 022726.

Landry, Z.C.; Giovanonni, S.J.; Quake, S.R.; Blainey, P.C. Optofluidic cell selection from complex microbial communities for single-genome analysis. Methods Enzymol (2013), 531, 61-90.

Blainey, P.C. The future is now: single-cell genomics of bacteria and archaea. FEMS Microbiol Rev (2013), 37, 3, 407-27.

Marshall, I.P.G.; Blainey, P.C.; Spormann, A.M.; Quake, S.R. A single-cell genome for Thiovulum sp. Applied and environmental microbiology (2012), 78, 24, 8555-8563.

Pamp, S.J.; Harrington, E.D.; Quake, S.R.; Relman, D.A.; Blainey, P.C. Single-cell sequencing provides clues about the host interactions of segmented filamentous bacteria (SFB). Genome Research (2012), 22, 6, 1107-19.



PRESENTATIONS

Midsummer Nights' Science 2012 Miniaturized lab-on-a-chip methods are being deployed as labor-saving devices in biological research, through the advent of a suite of microfluidics technologies. Microfluidics enables large-scale studies that provide the means to better understand, prevent, and treat human disease. In his 2012 Midsummer Nights' Science lecture, Paul Blainey discusses the promise of using microfluidics to transform our research infrastructure to operate more efficiently, while protecting the natural environment.
Watch the video!




COURSES

20.A04 - The Data-Brain Barrier
When it comes to data, there are megabytes, gigabytes, terabytes, yottabytes, and…yikes! Today we live with the legacy of previous decades' digital revolutions: rich, multidimensional datasets that present tremendous opportunities for discovery and understanding to the extent we can overcome challenges of scale, complexity, and varying degrees of confidence associated with statistical data. Science, commerce, finance, and government represent some of the fields confronted by large and/or complex datasets. This seminar will explore current thinking in information design for rendering multidimensional information on all scales in human-understandable forms. The design of information graphics is a critical element in extracting meaning from quantitative data and communicating this meaning in an expository manner. The principles of information design and strategies for communicating quantitative and statistical information graphically will be explored through historical examples, the popular media, and the scientific literature.
Stellar site

20.260/20.560 - Analysis and Presentation of Complex Biological Data
Illustrates best practices in the statistical analysis of complex biological datasets and the graphical representation of such analyses. Covers fundamental concepts in probability and statistical theory as well as principles of information design. Provides mathematical concepts and tools that enable students to make sound judgments about the application of statistical methods and to present statistical results in clear and compelling visual formats. Assignments focus on key concepts and their application to practical examples. Assumes basic knowledge of calculus and programming in MATLAB or R. Students taking graduate version complete additional assignments.
Stellar site

2.673/20.309/20.409 - Instrumentation and Measurement for Biological Systems
Sensing and measurement aimed at quantitative molecular/cell/tissue analysis in terms of genetic, biochemical, and biophysical properties. Methods include light and fluorescence microscopies, electronic circuits, and electromechanical probes (atomic force microscopy, optical traps, MEMS devices). Application of statistics, probability, signal and noise analysis, and Fourier techniques to experimental data.
Stellar site

20.345 - Bioinstrumentation Project Lab
In-depth examination of instrumentation design, principles and techniques for studying biological systems, from single molecules to entire organisms. Lectures cover optics, advanced microscopy techniques, electronics for biological measurement, magnetic resonance imaging, computed tomography, MEMs, microfluidic devices, and limits of detection. Students select two lab exercises during the first half of the term and complete a final design project in the second half. Lab emphasizes design process and skillful realization of a robust system.
Stellar site

20.415 - Physical Biology
Develops and applies principles of probability and physical chemistry to molecular and cellular biological systems. Information theory is used to analyze sequence conservation and coevolution, statistical mechanics is used to treat binding equilibria and biopolymer conformation, and transition-state theory is used to analyze kinetics of rate processes in the cell. Example case studies include transcription factor binding and target site recognition in DNA, cooperative binding of ligands to cell surface receptors, and DNA and RNA structure and dynamics in viruses, bacteria, and eukaryotic cells. Quantitative experimental assays to measure protein and nucleic acid structure and dynamics are discussed in detail.
Stellar site

20.440 - Biological Networks
This class analyzes complex biological processes from the molecular, cellular, extracellular, and organ levels of hierarchy. Emphasis is placed on the basic biochemical and biophysical principles that govern these processes. Examples of processes to be studied include chemotaxis, the fixation of nitrogen into organic biological molecules, growth factor and hormone mediated signaling cascades, and signaling cascades leading to cell death in response to DNA damage. In each case, the availability of a resource, or the presence of a stimulus, results in some biochemical pathways being turned on while others are turned off. The course examines the dynamic aspects of these processes and details how biochemical mechanistic themes impinge on molecular/cellular/tissue/organ-level functions. Chemical and quantitative views of the interplay of multiple pathways as biological networks are emphasized. Student work culminates in the preparation of a unique grant application in an area of biological networks.
Stellar site


Lab Position

Education

Email

Research Interest




Open positions are posted by Broad HR.

For further questions or appointments, please contact:

Emily Botelho
ebotelho'at'broadinstitute.org
(617) 714-7131

Our lab space and offices are located on the second floor of the Broad Institute.
Rooms 2175R-2175AB
415 Main Street
Cambridge, MA 02142


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Paul Blainey

Lab members:
Paul Blainey
Soohong Kim
Kan Xiong
David Feldman
Tony Kulesa
Georgia Lagoudas
Nav Ranu
Lily Xu
Leanna Morinishi



Assistant Professor of Biological Engineering
Core Member, Broad Institute of Harvard and MIT

Education:
Some areas of interest:
  • New applications of microfluidics in single-cell and single-molecule science
  • A microfluidic platform to connect high-resolution image data with molecular data at the microscale


  • Soohong Kim

    Lab members:
    Paul Blainey
    Soohong Kim
    Kan Xiong
    David Feldman
    Tony Kulesa
    Georgia Lagoudas
    Nav Ranu
    Lily Xu
    Leanna Morinishi



    Postdoctoral Associate
    Broad Institute of Harvard and MIT

    Education:
    Soohong Kim is a postdoctoral associate who investigates black sheep.


    Kan Xiong

    Lab members:
    Paul Blainey
    Soohong Kim
    Kan Xiong
    David Feldman
    Tony Kulesa
    Georgia Lagoudas
    Nav Ranu
    Lily Xu
    Leanna Morinishi



    Postdoctoral Associate
    Broad Institute of Harvard and MIT

    Education:


    David Feldman

    Lab members:
    Paul Blainey
    Soohong Kim
    Kan Xiong
    David Feldman
    Tony Kulesa
    Georgia Lagoudas
    Nav Ranu
    Lily Xu
    Leanna Morinishi



    Graduate Student
    MIT Physics

    Education:
    Interests include:
  • Arrayed microfluidics for genome engineering
  • Theoretical beekeeping


  • Tony Kulesa

    Lab members:
    Paul Blainey
    Soohong Kim
    Kan Xiong
    David Feldman
    Tony Kulesa
    Georgia Lagoudas
    Nav Ranu
    Lily Xu
    Leanna Morinishi



    Graduate Student
    MIT Biological Engineering

    Education:
    Interests include:
  • Bio-inspired approach to drugging transcription with DNA binders


  • Georgia Lagoudas

    Lab members:
    Paul Blainey
    Soohong Kim
    Kan Xiong
    David Feldman
    Tony Kulesa
    Georgia Lagoudas
    Nav Ranu
    Lily Xu
    Leanna Morinishi



    Graduate Student
    MIT Biological Engineering

    Education:
    Interests include:
  • Medical implications of the pulmonary microbiome


  • Lily Xu

    Lab members:
    Paul Blainey
    Soohong Kim
    Kan Xiong
    David Feldman
    Tony Kulesa
    Georgia Lagoudas
    Nav Ranu
    Lily Xu
    Leanna Morinishi



    Graduate Student
    MIT Biological Engineering

    Education:
    Interests include:
  • Single cell solid phase DNA amplification


  • Leanna Morinishi

    Lab members:
    Paul Blainey
    Soohong Kim
    Kan Xiong
    David Feldman
    Tony Kulesa
    Georgia Lagoudas
    Nav Ranu
    Lily Xu
    Leanna Morinishi



    Research Associate
    Broad Institute of Harvard and MIT

    Education:
    Interests include:
  • Improving single cell whole genome amplification