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
- 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.
- 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.
- 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
- 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
- Cohen, B.E., Grabe, M., and Jan, L.Y. Answers
and questions from the KvAP structures. Neuron 39,
395-400 (2003).
- 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
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