About the Perkins Group

In the Perkins group, we develop and apply high-precision single-molecule techniques—atomic force microscopy (AFM) and optical traps—to address outstanding questions in a wide range of biological systems. Ongoing projects include elucidating the energetics and folding dynamics of membrane proteins embedded in their native lipid bilayer, characterizing the force needed to extract tubulin from a microtubule, probing the nanomechanics of myosin, and studying the motion of helicases along DNA. Our biological goals often motivate improvements in single-molecule techniques, such as developing focused-ion-beam-modified AFM cantilevers, an optical-trapping microscope with 1 Å stability in 3D, efficient site-specific conjugation strategies, and novel DNA- and protein-based constructs.

Research Highlights

  • Model of the type three secretion system in Salmonella Bacteria

    The Forces involved in Folding Proteins

    In a new paper, JILA physicist Thomas Perkins collaborated with CU Biochemistry Prof. Marcello Sousa to dissect the mechanisms of how certain bacteria become more virulent. The research brings together the Perkins lab expertise in…
    Read More

  • AFM tip unfolding protein membranes

    Grabbing Proteins by the Tail

    "Unraveling" cell membrane proteins could help us understand how to build better drugs and treatments for disease.


    Read More
  • AFM apex runs over a strand of DNA

    DNA imaging, ready in five minutes

    It's tough to get tightly-wound balls of DNA to lay down flat and straighten out to get their picture taken. A new technique from the Perkins group gets a crisp, clear picture in just five minutes.


    Read More
  • An artist's illustration of an A.F.M. pulling apart an HIV hairpin

    Pulling apart HIV

    JILA researchers have demonstrated a much easier, faster and more precise way to understand the structure and function of the HIV RNA molecule, especially the HIV RNA hairpin. Furthermore, the techniques developed for this research…
    Read More

  • Thumbnail

    Precision Biomechanics

    The Perkins group has made dramatic advances in the use of Atomic Force Microscopes (AFMs) to study large single biomolecules, such as proteins and nucleic acids (DNA, RNA), that are important for life. After previously improving AFM…
    Read More

  • Thumbnail

    Vision Quest

    The Perkins group continues to extend the performance of its unique Atomic Force Microscope (AFM) technology, revealing for the first time a dozen new short-lived intermediate states in the folding and unfolding of a membrane protein…
    Read More

  • Thumbnail

    The Land of Enhancement: AFM Spectroscopy

    The Perkins Group has demonstrated a 50-to-100 times improvement in the time resolution for studying the details of protein folding and unfolding on a commercial Atomic Force Microscope (AFM). This enhanced real time probing of protein…
    Read More

  • Thumbnail

    The Measure of Small Things

    Fellow Tom Perkins’ group is significantly closer to realizing its long-standing dream of using atomic force microscopy (AFM) to study how membrane proteins fold and unfold. Historically, scientists have used AFM to measure the…
    Read More

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    bR Phone Home

    The groups of Fellow Adjoint Markus Raschke and Fellow Tom Perkins joined forces recently to shine light onto a bacterial membrane protein called bacteriorhodopsin (bR). They used a new infrared (IR) light imaging system with a spatial…
    Read More

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    Going for the Gold

    Gold glitters because it is highly reflective, a quality once considered important for precision measurements made with gold-coated probes in atomic force microscopy (AFM). In reality, the usual gold coating on AFM probes is a major…
    Read More

  • Thumbnail

    Upending Conventional Wisdom

    In science, it can be fun and interesting to upend conventional wisdom. A good example is what just happened to a widely accepted explanation for overstretching of double-stranded DNA (dsDNA). Overstretching occurs suddenly when…
    Read More

  • Thumbnail

    The Guiding Light

    Atomic force microscopy (AFM) just got a whole lot more efficient for studying proteins and other biomolecules. Graduate student Allison Churnside, former research associate Gavin King, and Fellow Tom Perkins recently used a laser to…
    Read More

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    How to Marry a Microscope

    The most important step for a microscope wanting to marry another microscope is finding the right partner. A professional matchmaker, such as the Perkins lab, might be just the ticket. The group recently presided over the nuptials of…
    Read More

  • Thumbnail

    DNA: Force of Nature

    The Perkins group is helping to develop DNA as a force standard for the nano world. Polymers of DNA act like springs, and DNA's elasticity may one day provide a force standard from 0.1–10 piconewtons (pN). One pN is the force exerted…
    Read More

  • Thumbnail

    Gold Fever

    Life can be challenging on the biophysics research frontier. Consider gold nanoparticles as a research tool, for example. Gold is ductile and malleable as well as being a good conductor of heat and electricity. Its unique chemistry…
    Read More

  • Thumbnail

    Sightseeing along a DNA Strand

    Lora Nugent-Glandorf and Tom Perkins have come up with an optical trap motion detector that can "see" protein motors moving one base at a time along a DNA helix. For some time scientists have been able to make optical traps that can…
    Read More

Research Highlights

  • Model of the type three secretion system in Salmonella Bacteria

    The Forces involved in Folding Proteins

    In a new paper, JILA physicist Thomas Perkins collaborated with CU Biochemistry Prof. Marcello Sousa to dissect the mechanisms of how certain bacteria become more virulent. The research brings together the Perkins lab expertise in…
    Read More

  • AFM tip unfolding protein membranes

    Grabbing Proteins by the Tail

    "Unraveling" cell membrane proteins could help us understand how to build better drugs and treatments for disease.


    Read More
  • AFM apex runs over a strand of DNA

    DNA imaging, ready in five minutes

    It's tough to get tightly-wound balls of DNA to lay down flat and straighten out to get their picture taken. A new technique from the Perkins group gets a crisp, clear picture in just five minutes.


    Read More
  • An artist's illustration of an A.F.M. pulling apart an HIV hairpin

    Pulling apart HIV

    JILA researchers have demonstrated a much easier, faster and more precise way to understand the structure and function of the HIV RNA molecule, especially the HIV RNA hairpin. Furthermore, the techniques developed for this research…
    Read More

  • Thumbnail

    Precision Biomechanics

    The Perkins group has made dramatic advances in the use of Atomic Force Microscopes (AFMs) to study large single biomolecules, such as proteins and nucleic acids (DNA, RNA), that are important for life. After previously improving AFM…
    Read More

  • Thumbnail

    Vision Quest

    The Perkins group continues to extend the performance of its unique Atomic Force Microscope (AFM) technology, revealing for the first time a dozen new short-lived intermediate states in the folding and unfolding of a membrane protein…
    Read More

  • Thumbnail

    The Land of Enhancement: AFM Spectroscopy

    The Perkins Group has demonstrated a 50-to-100 times improvement in the time resolution for studying the details of protein folding and unfolding on a commercial Atomic Force Microscope (AFM). This enhanced real time probing of protein…
    Read More

  • Thumbnail

    The Measure of Small Things

    Fellow Tom Perkins’ group is significantly closer to realizing its long-standing dream of using atomic force microscopy (AFM) to study how membrane proteins fold and unfold. Historically, scientists have used AFM to measure the…
    Read More

  • Thumbnail

    bR Phone Home

    The groups of Fellow Adjoint Markus Raschke and Fellow Tom Perkins joined forces recently to shine light onto a bacterial membrane protein called bacteriorhodopsin (bR). They used a new infrared (IR) light imaging system with a spatial…
    Read More

  • Thumbnail

    Going for the Gold

    Gold glitters because it is highly reflective, a quality once considered important for precision measurements made with gold-coated probes in atomic force microscopy (AFM). In reality, the usual gold coating on AFM probes is a major…
    Read More

  • Thumbnail

    Upending Conventional Wisdom

    In science, it can be fun and interesting to upend conventional wisdom. A good example is what just happened to a widely accepted explanation for overstretching of double-stranded DNA (dsDNA). Overstretching occurs suddenly when…
    Read More

  • Thumbnail

    The Guiding Light

    Atomic force microscopy (AFM) just got a whole lot more efficient for studying proteins and other biomolecules. Graduate student Allison Churnside, former research associate Gavin King, and Fellow Tom Perkins recently used a laser to…
    Read More

  • Thumbnail

    How to Marry a Microscope

    The most important step for a microscope wanting to marry another microscope is finding the right partner. A professional matchmaker, such as the Perkins lab, might be just the ticket. The group recently presided over the nuptials of…
    Read More

  • Thumbnail

    DNA: Force of Nature

    The Perkins group is helping to develop DNA as a force standard for the nano world. Polymers of DNA act like springs, and DNA's elasticity may one day provide a force standard from 0.1–10 piconewtons (pN). One pN is the force exerted…
    Read More

  • Thumbnail

    Gold Fever

    Life can be challenging on the biophysics research frontier. Consider gold nanoparticles as a research tool, for example. Gold is ductile and malleable as well as being a good conductor of heat and electricity. Its unique chemistry…
    Read More

  • Thumbnail

    Sightseeing along a DNA Strand

    Lora Nugent-Glandorf and Tom Perkins have come up with an optical trap motion detector that can "see" protein motors moving one base at a time along a DNA helix. For some time scientists have been able to make optical traps that can…
    Read More

Research Areas

  • We are studying the energetics that stabilize membrane proteins by folding and unfolding individual molecules using AFM. By using cantilevers optimized for 1-µs resolution, we can measure the unfolding of individual molecules of the model membrane protein bacteriorhodopsin (bR) at 100-fold higher time resolution and 10-fold higher force precision than prior studies. This improvement in instrumental performance has allowed us to identify the energy barriers between states and to distinguish among obligatory, non-obligatory, and off-pathway intermediates.

  • Over the last 50 years, the search to understand the protein-folding process has blossomed into a large, interdisciplinary field. More recently, mechanobiology—the study of the mechanical forces exerted on molecules and cells—has also become an important and rapidly growing field. In both fields, the energy landscape provides the framework to describe the process of protein folding and how proteins respond to force. Local and global minima on this landscape represent intermediate and final states, respectively. In single molecule force spectroscopy (SMFS), regions of the energy landscape away from the global minimum are probed by perturbing a biomolecule with applied force, just as global denaturants such as urea or temperature are used in traditional biochemical assays.

  • We apply optical traps and AFM to yield mechanistic insight into how enzymes move along and bind to DNA as well as DNA’s fundamental mechanical properties. We developed an actively stabilized, optical-trapping microscope and applied it to study RecBCD, a helicase, at 1-bp resolution. More recently, we developed new techniques for AFM imaging of DNA in liquid and applied them to visualize the Polycomb repressive complex 2 (PRC2) bound to DNA. These new AFM measurements build on extensive prior studies of Polycomb group proteins by showing that PRC2 compacts DNA independent of its methyltransferase activity.

  • Single-molecule studies are a powerful means to study the dynamics and energetics of biological molecules and biomolecular complexes. These studies are limited by instrumentation resolution and assay efficiency. Historically, AFM was considered to have force resolution of ~5–20 pN and to suffer from significant instrumental drift. Over the last 15 years, we have substantially improved the precision, stability, and temporal resolution of bioAFM, culminating in studying membrane-protein unfolding with a 100-fold improvement in time resolution and a 10-fold improvement in force precision.

In the Spotlight

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November 08, 2021: Perkins lab awarded a new $1.15 M grant from the NSF
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Photo of JILA Fellows Graeme Smith and THomas Perkins
September 16, 2021: JILA Fellows Thomas Perkins and Graeme Smith win the 2021 Outstanding Postdoc Mentor Award
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March 30, 2021: Congrats to David on his PNAS paper studying energetics of bacteriorhodopsin point mutants in their native lipid bilayer
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March 17, 2021: Congrats to Devin and Marc-Andre for their PNAS paper showing biological insights can be derived for fast folding, mechanically labile proteins despite artifacts in AFM based force spectroscopy.
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JILA Address

We are located at JILA: A joint institute of NIST and the University of Colorado Boulder.

Map | JILA Phone: 303-492-7789 | Address: 440 UCB, Boulder, CO 80309