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		Search Text: Home/< Back ToThe Science/Single Molecule Biophysics
  Single Molecule Biophysics
    In the Laboratory of Single Molecule Biophysics, led by Dr. Keir C. Neuman, techniques---including optical and magnetic tweezers and fluorescence imaging, in combination with conventional molecular biology approaches---are employed to answer fundamental questions concerning enzyme function and regulation.
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          Keir Neuman
  Keir Neuman, Ph.D.
          Senior Investigator
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      Meet the Team
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  Senior Investigator Research Interests
            
  Research Interests
              Enzymes are typically studied in ensembles. Enzyme mechanism has traditionally been elucidated from biochemical and structural experiments that involve thousands or millions of molecules. Enzymes, however, are complex molecular machines that, when subjected to individual scrutiny, reveal features that cannot be ascertained from ensemble approaches. Single-molecule visualization and manipulation techniques are at the technological forefront of biological inquiry; these techniques can probe distances on the sub-nanometer (10-9 M) scale and forces on the piconewton (10-12 N) scale with millisecond temporal resolution. Dr. Neuman employs these single-molecule techniques—including optical and magnetic tweezers and fluorescence imaging, in combination with molecular biology, biochemical, and molecular dynamics approaches—to answer fundamental questions concerning enzyme function and regulation. His research program is underpinned by single-molecule instrumentation that his laboratory designs and builds to elucidate enzyme mechanisms at the molecular level.

Approximately two meters of DNA is compacted into the nucleus of a human cell, which leads to topological complications during replication, transcription, and segregation of chromosomes. Topoisomerases are essential enzymes that regulate DNA topology and are important chemotherapeutic and antibiotic drug targets; Dr. Neuman focuses on elucidating the molecular mechanisms of topoisomerase activity and inhibition by chemotherapeutic agents.

Topoisomerases interact with many other enzymes that regulate DNA. Dr. Neuman is extending the use of single-molecule techniques to dissect multi-enzyme complex formation and activity. For this work, he focuses on the combination of RecQ helicase and topoisomerase III, which is a conserved interaction in organisms ranging from E. coli through humans that plays important roles in homologous recombination, genome stability, chromosome segregation.

The organization of the genome has emerged as an important regulator of physiological processes at multiple scales. An important aspect of this organization stems from the topology of the DNA; how it is over or underwound, knotted, or linked. Dr. Neuman employs single-molecule manipulation approaches to understand the mechanics and dynamics of DNA under topological constraints. Of particular interest recently is understanding how DNA mismatches or damaged bases impact the topology of DNA and how this may facilitate DNA repair in vivo.

Keir Neuman CV



Videos

Single Molecule Biophysics - Keir Neuman, NIH Scientist

Keir Neuman, Ph.D., applies physics to transform the field of biology at the National Institutes of Health (NIH) Intramural Research Program (IRP). Dr. Neuman is a Principal Investigator in the Laboratory of Single Molecule Biophysics at the National Heart Lung and Blood Institute (NHLBI).
  Featured Publications
                Biocompatible Fluorescent Nanodiamonds as Multifunctional Optical Probes for Latent Fingerprint Detection.
            Authors:Jung HS, Cho KJ, Ryu SJ, Takagi Y, Roche PA, Neuman KC.
                                                                                                                        
            ACS Appl Matter Interfaces.
      
                2020 Feb 05;12(5):6641-6650
        Read Publication
                      Mapping DNA Topoisomerase Binding and Cleavage Genome Wide Using Next-Generation Sequencing Techniques
            Authors:McKie SJ, Maxwell A, Neuman KC.
                                                                                                                        
            Genes (Basel). 
      
                2020 Jan 13;11(1):92
        Read Publication
                      Bimodal Actions of a Naphthyridone/Aminopiperidine-Based Antibacterial That Targets Gyrase and Topoisomerase IV.
            Authors:Gibson EG, Oviatt AA, Cacho M, Neuman KC, Chan PF, Osheroff N.
                                                                                                                        
            Biochemistry.
      
                2019 Nov 05;58(44):4447-4455
        Read Publication
                      Homology sensing via non-linear amplification of sequence-dependent pausing by RecQ helicase.
            Authors:Seol Y, Harami GM, Kovács M, Neuman KC.
                                                                                            
            Elife.
      
                2019 Aug 29;8:e45909
        Read Publication
                      Combined Magnetic Tweezers and Micro-mirror Total Internal Reflection Fluorescence Microscope for Single-Molecule Manipulation and Visualization
            Authors:Seol Y, Neuman KC.
                                                                                            
            Methods Mol Biol.
      
                2019 Jan 01;1665:297-316
        Read Publication
  Meet the Team

    Keir Neuman

            Keir Neuman, Ph.D.
                Senior Investigator
                Keir Neuman graduated cum laude with a B.A. in physics and applied math from the University of California, Berkeley in 1994 and received his Ph.D. in physics from Princeton University in 2002. He conducted postdoctoral research with Steven Block at Stanford University from 2002 to 2004, and was a Human Frontiers Fellow with David Bensimon and Vincent Croquette at the Laboratoire de Physique Statistique at the École Normale Supérieure in Paris, France from 2004 to 2007. Dr. Neuman joined the NHLBI as a tenure-track Investigator in 2007 and was promoted to senior investigator in 2015. He is a member of the Biophysical Society, the American Physical Society, the Optical Society of America, and the American Chemical Society. He is an editorial board member of the Biophysical Journal.
    
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    50 South DrBethesda, MD 20814United States
        Phone:
                    301-480-4076
                Fax:
            301-402-3404
  Yeonee Seol
    
            Yeonee Seol, Ph.D.
        

    Staff Scientist

        seoly@mail.nih.gov
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            Haksung  Jung, Ph.D.
        

    Postdoctoral Fellow

        haksung.jung@nih.gov
            Parth
    
            Parth Desai
        

    Graduate Student
            Rachel
    
            Rachel Kim
        

    Postbaccalaureate Fellow
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            Haksung Jung, Ph.D.
        

    Postdoctoral Fellow
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            Jonathan Silver, M.D.
        

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