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Faculty
Leslie M. Loew
Professor of Cell Biology
Director, Center for Cell Analysis and Modeling
les@volt.uchc.edu
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.
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