Neuronal structural biology is the focus area of Dr. Zhang's
laboratory. We aim to understand the molecular mechanisms governing synaptic
signal transduction complex organization, dynamic regulations of synaptic complex
assemblies, and trafficking of proteins involved in synaptic signaling using a
combination of NMR spectroscopy, X-ray crystallography, biochemistry, molecular
biology and cell biology approaches. The second focus of the lab is to elucidate
the molecular basis of protein complexes regulating cell polarity establishment
and maintenance.
In the first area, we are primarily working on synaptic signal transduction
complex organizations by various scaffold proteins (e.g. PDZ domain proteins). In
postsynaptic neurons, signal transduction complexes are often organized into large
multi-components assemblies (transducisomes). The proper organization of such
supramolecular complexes is critical for specificity and efficiency of signal
transmissions across synapses. We are also interested in the dynamics of various
signaling complex assemblies, by investigating regulated protein-protein
interactions in synapses.
In the second area, we are interested in how protein complexes
(e.g. the Par-3/Par-6/aPKC complex and the Usher complex) orchestrate the highly
polarized nature of a wide variety of eukaryotic cells including neurons and epithelia. Our
prime interest is to understand, from structural and biochemical angles, how these
complexes assemble with other cell polarity proteins and lipids in controlling cell
polarity. We are also interested in why mutations of polarity proteins are linked with
human diseases.
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