Haining Zhong, Ph.D.
Haining Zhong earned his B.A. in Biological Science and Biotechnology, and B.Eng. in Electronics and Computer Science from Tsinghua University in Beijing, China in 1996. He received his Ph.D. in Neuroscience from the Johns Hopkins University School of Medicine in 2002. Zhong did postdoctoral training at the Cold Spring Harbor Laboratory and then at the Janelia Farm Research Campus of the Howard Hughes Medical Institute. In 2009 he was appointed as an assistant scientist at the Vollum Institute and was promoted to scientist in 2015.
Summary of Current Research
Our brain is a complex network consisting of billions of neurons. These neurons communicate with one another through trillions of very specialized connections called chemical synapses. These synapses and their experience-dependent plasticity are thought to be the fundamental mechanisms underlying animal’s behavior, adaptation, learning and memory. We are interested in the mechanisms by which the strength of a synapse is set and regulated at the cellular and molecular level.
Synaptic function and plasticity require the regulation and interaction of myriad synaptic proteins. Merely knowing the identity of these players is not sufficient to understand their roles in synaptic functions. As many of these proteins are strategically and dynamically organized in neurons, an investigation of their spatiotemporal organization is necessary to understand how neuronal communication works. Our current focus, then, is to systematically characterize the abundance, stoichiometry, localization and activity of critical synaptic proteins and how they are modulated by neuronal activity.
Because the scale of protein architecture can span several orders of magnitude, from a few nanometers to tens of micrometers, we use several complementary imaging approaches. Two-photon microscopy allows us to examine protein distribution in live neurons in cortical slices at diffraction-limited resolution (~ 0.5 µm); super-resolution, photoactivated localization microscopy (PALM) enables the examination of protein distribution and movement at 20 nm resolution; and two-photon fluorescence lifetime imaging microscopy (2PFLIM), which quantifies FRET, is used to examine the activity of signaling reporters and protein-protein interactions at a scale less than 8 nm. These imaging approaches are combined with electrophysiological recording, genetic labeling and manipulation of individual neurons, and novel optical and optogenetic tools for physiologically-relevant stimuli. The goal is to provide an architectural basis of the synapse for understanding synaptic function and plasticity.
On-going studies include how protein kinase A (PKA), a broad spectrum kinase that regulates many aspects of neuronal functions, is strategically positioned to achieve their function and specificity. We are also interested in how PKA is activated and inactivated by various forms of neuronal activity. Finally, we are examining the structure and experience-dependent dynamics of the postsynaptic density using a PSD95-GFP knock-in mouse.
Zhong, H. (2015) Applying superresolution localization-based microscopy to neurons. Synapse 69:283-294.
Fortin, D.A., Tillo, S.E., Yang, G., Rah, J.C., Melander, J.B., Bai, S., Soler-Cedeño, O., Qin, M., Zemelman, B.V., Guo, C., Mao, T., and Zhong H. (2014) Live imaging of endogenous PSD-95 using ENABLED: a conditional strategy to fluorescently label endogenous proteins. J. Neurosci. 34:16698-16712.
Zhong, H. (2010) Photoactivated localization microscopy (PALM): an optical technique for achieving ~10-nm resolution. Cold Spring Harb. Protoc. 2010(12):pdb.top91.
Zhong, H., Sia, G.M., Sato, T.R., Gray, N.W., Mao, T., Khuchua, Z., Huganir, R.L. and Svoboda, K. (2009) Subcellular dynamics of type II PKA in neurons. Neuron 62:363-374.
Do, M.T., Kang, S.H., Xue, T., Zhong, H., Liao, H.W., Bergles, D.E. and Yau, K.W. (2009) Photon capture and signaling by melanopsin retinal ganglion cells. Nature 457:281-287.
Ji, N., Shroff, H., Zhong, H. and Betzig, E. (2008) Advances in the speed and resolution of light microscopy. Curr. Opin. Neurobiol. 18:605-616.
Harvey, C.D., Yasuda, R., Zhong, H. and Svoboda, K. (2008) The spread of Ras activity triggered by activation of a single dendritic spine. Science 321:136-140.
Yasuda, R., Harvey, C.D., Zhong, H., Sobczyk, A., van Aelst, L. and Svoboda, K. (2006) Supersensitive Ras activation in dendrites and spines revealed by two-photon fluorescence lifetime imaging. Nature Neurosci. 9:283-291.
Fu, Y., Zhong, H., Wang, M.H., Luo, D.G., Liao, H.W., Maeda, H., Hattar, S., Frishman, L. J. and Yau, K.W. (2005) Intrinsically photosensitive retinal ganglion cells detect light with a vitamin A-based photopigment, melanopsin. Proc. Natl. Acad. Sci. USA 102:10339-10344.
Zhong, H., Lai, J. and Yau, K.W. (2003) Selective heteromeric assembly of cyclic nucleotide-gated channels. Proc. Natl. Acad. Sci. USA 100:5509-5513.
Zhong, H., Molday, L.L., Molday, R.S. and Yau, K.W. (2002) The heteromeric cyclic nucleotide-gated channel adopts a 3A:1B stoichiometry. Nature 420:193-198.
Munger, S.D., Lane, A.P., Zhong, H., Leinders-Zufall, T., Yau, K.W., Zufall, F. and Reed, R.R. (2001) Central role of the CNGA4 channel subunit in Ca2+-calmodulin-dependent odor adaptation. Science 294:2172-2175.
Grunwald, M.E., Zhong, H., Lai, J. and Yau, K.W. (1999) Molecular determinants of the modulation of cyclic nucleotide-activated channels by calmodulin. Proc. Natl. Acad. Sci. USA 96:13444-13449.