Bruce Cohen

Scientist, Biological Nanostructures Facility
510.486.6640, BECohen@lbl.gov

Research interests

I am interested in creating new fluorescent probes and imaging reagents for biological applications ranging from neuroscience and cell biology to fundamental questions of protein biophysics.  My research aims to develop new methods for targeting luminescent nanoparticles to specific cellular agents, or to create novel fluorescent nanostructures useful in biological imaging.

Current projects              

  1. Functionalization of nanoparticle surfaces with bioactive molecules
    We are developing novel reagents and methods for coating nanoparticles with proteins, oligonucleotides, and other bioactive molecules. This begins with new amphiphilic coatings that solubilize the hydrophobic inorganic crystals in water, improve their brightness, and provide reactive bioconjugation handles. Bioactive molecules can then be attached, including DNA for live-cell visualization of RNA, chemical groups that can selectively react with specific protein post-translational modifications, peptides to target epitope tags introduced into cellular proteins, and drugs that can report on the activity of specific cellular enzymes and channels.
  2. Single-molecule imaging with quantum dots
    The superior brightness and stability of quantum dots compared to traditional organic fluorophores makes them ideal for tracking single particles on or in cells.  Using total internal reflection microscopy (TIRFM), we are using biocoated quantum dots to study activity-dependent RNA trafficking and membrane changes in developing neurons.  In addition to quantum dots, as part of a collaboration with Dmitri Talapin of the Inorganic facility, we are studying other nanoparticles for improved spectral and biochemical properties in these experiments. 
  3. New semi-synthetic fluorescent nanostructures
    As a means of labeling specific cellular proteins with far red and near infrared dyes for imaging, we are using phage display to identify short genetically encoded sequences that can act as receptors for specific fluorophores. (The phage library is courtesy of Garry Nolan, Stanford University). Phage display permits the screening of a large number of sequences (about 1012) for binding to the fluorophores, and standard molecular biological techniques permit fusion of these sequences with a protein of interest. This project includes synthesis of novel organic dyes that are ideal for protein labeling in live cells, phage display genetics, and cellular imaging of labeled proteins.                  
Selected publications
  1. Cohen, B.E., Pralle, A., Yao, X., Swaminath, G., Gandhi, C., Jan, Y.N., Kobilka, B.K., Isacoff, E.Y., and Jan, L.Y.  A fluorescent probe designed for studying protein conformational change. Proceedings of the National Academy of Science 102, 965-970 (2005).http://www.pnas.org/cgi/reprint/102/4/965
  2. Cohen, B.E., Grabe, M., and Jan, L.Y.  Answers and questions from the KvAP structures.  Neuron 39, 395-400 (2003).
  3. Cohen, B.E., McAnaney, T.B., Park, E.S., Jan, Y.N., Boxer, S.G., and Jan, L.Y.  Probing protein electrostatics with a synthetic fluorescent amino acid.  Science 296, 1700-1703 (2002). http://www.sciencemag.org/cgi/reprint/296/5573/1700.pdf
Education
A.B., Princeton University
Ph.D., University of California Berkeley, Daniel E. Koshland, Jr.
Postdoctoral Fellowship, University of California San Francisco and HHMI, Lily Y. Jan