Research
interests
Our research focuses on synthesis of biologically active
nanostructures and their applications to biological imaging. A major
focus is developing novel nanoparticles with useful and unusual optical
properties.
Current projects:
- We have developed caged quantum dots, which
are non-luminescent under typical microscopic illumination but can
be activated with stronger pulses of UV light. These nanoparticles
are hybrids of hard and soft materials, and their unique optical
properties arise from the interaction between a classic organic caging
group and a semiconducting QD. These nanoparticles endow quantum
dots with one of the most useful properties of bioimaging probes—the
ability to be switched on with light—and promise to be valuable
in a variety of applications, including superresolution imaging,
time-resolved live cell imaging, and selective spatial activation
for studying protein trafficking and polarized cells.
- We are developing a second type of nanoparticle (in collaboration
with Delia Milliron of the Inorganic Facility and Jim Schuck of
Imaging) with interesting optical properties for bioimaging, lanthanide-doped
upconverting nanoparticles (UCNPs). These particles absorb 2 photons
in the near infrared (nIR) and emit at shorter wavelengths in the
visible or nIR. This property will be exceptionally valuable for
bioimaging: compared to visible or UV, nIR radiation is less damaging
to cells, produces much less autofluorescent background, and scatters
less, allowing deeper tissue penetration or even whole animal imaging.
We have developed a synthesis of monodisperse UCNPs in the desired
size regime and a simple procedure for transferring them to water.
With these, we have recorded the first single molecule images of
UCNPs, showing that they do not blink (as QDs and many organic
probes do) and that they posses remarkable photostability, resisting
photobleaching long after organics and QDs do. We are finding other
interesting spectral characteristics at the single-molecule level,
and we are currently exploring UCNPs for cellular imaging experiments,
as well as other advanced imaging applications.
- A third project
is to develop genetically encoded fluorescent nanostructures as
protein imaging tags. We are using phage panning to find peptide
sequences that bind to novel nIR organic fluorophores. Fusion of
these fluorophore-binding sequences to proteins of interest using
standard molecular biology techniques will provide a means of fluorescently
labeling intracellular proteins in live cells. For this project,
we have synthesized several new nIR dyes, two of which show exceptional
brightness, and we are identifying phage sequences that bind to
these dyes. The peptides will be structurally characterized in
complex with the dyes and then optimized into high-affinity sequences
that can be used as to form nano-fluorescent proteins in cells.
Selected publications
- S. Wu, G. Han, D.J. Milliron, S. Aloni, V. Altoe, D.V. Talapin,
B.E. Cohen, P.J. Schuck. Non-blinking and photostable upconverted
luminescence from single lanthanide-doped nanocrystals. PNAS, in
press.
G. Han, T. Mokari, C. Ajo-Franklin, B.E. Cohen. Caged quantum dots.
J. Am. Chem. Soc. 130, 15811-15813 (2008). http://pubs.acs.org/doi/full/10.1021/ja804948s
J.S. Salafsky, B.E. Cohen. A second-harmonic-active unnatural amino
acid as a structural probe of biomolecules on surfaces. J. Phys.
Chem. B 112, 15103–15107 (2008). http://pubs.acs.org/doi/full/10.1021/jp803703m
P. Abbyad, X. Shi, W. Childs, T.B. McAnaney, B.E Cohen, and S.G.
Boxer. Measurement of solvation responses at multiple sites in
a globular protein. J. Phys. Chem. B 111, 8269-8276 (2007). http://pubs.acs.org/doi/full/10.1021/jp0709104
B.E. Cohen, A. Pralle, X. Yao, G. Swaminath, C. Gandhi, Y.N. Jan,
B.K. Kobilka, E.Y. Isacoff, E.Y., and L.Y. Jan. A fluorescent probe
designed for studying protein conformational change. PNAS 102,
965-970 (2005). http://www.pnas.org/content/102/4/965.full
B.E. Cohen, T.B. McAnaney, E.S. Park, Y.N. Jan, S.G. Boxer, and
L.Y. Jan. Probing protein electrostatics with a synthetic fluorescent
amino acid. Science 296, 1700-1703 (2002). http://www.sciencemag.org/cgi/content/full/296/5573/1700
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 |
