Areas of Interest
Research in this laboratory encompasses several projects. We
have a longstanding effort aimed at developing and
characterizing fluorescent probes of membrane potential.
Although this effort is continuing, we are now particularly
focused on studies of the non-linear optical properties of the
dyes, including second harmonic generation as an alternative to
fluorescence as a probe of membrane potential. A second project
is aimed at elucidating how electrical potentials may vary along
neuronal surfaces and the cell physiological consequences of
such heterogeneities. Among the consequences that have been
suggested by our studies are directed neurite outgrowth and
local sensitization of voltage-dependent ion channels.
Quantitative digital imaging microscopy is combined with patch
clamp recording in these studies and has revealed roles for
intracellular calcium changes in the mechanisms of these
phenomena. Finally, we are very excited about a project called
the "Virtual Cell", in which we have created a framework for
using computer simulation to explore cell biological mechanisms.
The models are built naturally from experimental images of cell
and subcellular structures combined with biochemical and
electrophysiological data. Among the published ways we have used
the “Virtual Cell” system are to explain the pattern of
cytosolic calcium waves evoked by hormonal stimulation of a
neuronal cell and the regulation of nucleocytoplasmic transport.
Lab Rotation Projects
Students who wish to formulate their own novel questions
about neuronal cell biology are more than welcome. In addition
the following projects are available:
1. We are interested in the initial calcium signals
that initiate long-term depression in cerebellar Purkinje cells.
We will examine the calcium dynamics in the dendrites and their
spines using 2-photon microscope imaging of calcium indicators.
Rotation projects could involve either experimental work on the
calcium imaging or computational modeling with the Virtual Cell
software related to how the morphology of the Purkinje cell
regulates calcium signals.
2. We have discovered a powerful method for
visualizing lipid domains using microscopy and a membrane
staining fluorescent dye. We need a rotation student to
investigate if a similar dye will display improved properties.
This project will introduce the student to the biophysics of
lipid rafts and will teach him/her confocal and 2-photon
microscopy.
Selected Publications
Matiukas, A., B. G. Mitrea, A. M. Pertsov, J. P. Wuskell, M.-d.
Wei, J. Watras, A. C. Millard, and L. M. Loew. 2006. New Near
Infrared Optical Probes of Cardiac Electrical Activity. Am. J.
Physiol. in press.
Jin, L., A. C. Millard, J. P. Wuskell, X. Dong, D. Wu, H. A.
Clark and L. M. Loew. 2006. Characterization and Application of
a New Optical Probe for Membrane Lipid Domains. Biophys. J., in
press.
Milojkovic B.A., Wuskell J., Loew L. M., and Antic S.A.,
2005. Initiation of sodium spikelets in basal dendrites of
neocortical pyramidal neurons. J. Memb. Biol. in press.
Millard, A.C., Jin, L., Wuskell, J.P. Boudreau, D. M. Lewis,
A. and Loew, L. M., 2005. Wavelength- and Time-Dependence of
Potentiometric Non-linear Optical Signals from Styryl Dyes. J.
Memb. Biol. in press.
Mayya, V., and L.M. Loew. 2005. STAT module can function as a
biphasic amplitude filter. Systems Biology. 2:43-52.
Moraru, I.I., and L.M. Loew. 2005. Intracellular signaling:
spatial and temporal control. Physiology, 20: 169-179.
Millard, A.C., M. Terasaki, and L.M. Loew. 2005. Second
harmonic imaging of exocytosis at fertilisation. Biophys. J.,
88:L46-8.
Jin, L., A.C. Millard, J.P. Wuskell, H.A. Clark, and L.M.
Loew. 2005. Cholesterol enriched lipid domains can be visualized
by di-4-ANEPPDHQ with linear and non-linear optics. Biophys. J.
89: L4-6.
Watras, J., C.C. Fink, and L.M. Loew. 2005. Endogenous
Inhibitors of InsP3-induced Ca2+ Release in Neuroblastoma cells.
Brain Research. 1055:60-72.
Wuskell, J. P., D. Boudreau, M. D. Wei, L. Jin, R. Engl, R.
Chebolu, A. Bullen, K. D. Hoffacker, J. Kerimo, L. B. Cohen, M.
R. Zochowski, and L. M. Loew. 2005. Synthesis, spectra, delivery
and potentiometric responses of new styryl dyes with extended
spectral ranges. J. Neurosc. Meth. in press.
Hernjak, N., B. M. Slepchenko, K. Fernald, C. C. Fink, D.
Fortin, I. I. Moraru, J. Watras, and L. M. Loew, 2005. Modeling
and analysis of calcium signaling events leading to long-term
depression in cerebellar Purkinje cells. Biophys. J.
89:3790-3806.
Millard AC, Jin L, Wei M-d, Wuskell JP, Lewis A, Loew LM.
2004. Sensitivity of second harmonic generation from styryl dyes
to trans-membrane potential. Biophysical Journal 86:1169-76.
Obaid AL, Loew LM, Wuskell JP, Salzberg BM. 2004. Novel
naphthylstyryl-pyridinium potentiometric dyes offer advantages
for neural network analysis. J. Neurosci. Methods 134:179-90.
Wagner J, Fall CP, Hong F, Sims CE, Allbritton NL, Fontanilla
RA, Moraru II, Loew LM, Nuccitelli R. 2004. A wave of IP3
production accompanies the fertilization Ca2+ wave in the egg of
the frog, Xenopus laevis: theoretical and experimental support.
Cell Calcium 35:433-47.
Schaff, J. C., J. Carson and L. M. Loew. 2004. “Method for
modeling cellular structure and function,” United States Patent
6,708,141.
Fall, CP, Wagner, JM, Loew LM, Nuccitelli , R. 2004.
Cortically Restricted Production of IP3 Leads to Propagation of
the Ferilization Ca2+ Wave Along the Cell Surface in a Model of
the Xenopus Egg. J. Theor. Biol., 231:487-496.
Novak IL, Slepchenko BM, Mogilner A, Loew LM. 2004.
Cooperativity between cell contractility and adhesion. Phys Rev
Lett 93:268109-1-4. |
