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.

The Department of Biochemistry, HKUST has two high field NMR spectrometers (Varian Inova 500 MHz and 750 MHz) dedicated to structural biology.  Dr. Zhang's group is entitled to up to 50% of spectrometer time.  Our group has also built up computation facilities necessary for structural biology (Unix workstations, PCs and Mac computer).  Our lab has access to major proteomic research facilities (e.g. high resolution, high throughput mass spectrometers) via collaboration projects.

We have an active biochemistry and molecular biology "wet" lab with extensive protein purification facilities (FPLC, HPLC, low pressure LC systems). 

Publications:

Lifeng Pan., Yan, J., Wu, L. and Zhang, M. (2009) ":Assembling Stable Hair-Cell Tip Link Complex via Multi-dentate Interactions between Harmonin and Cadherin23" PNAS. 106 5575-5580
[Abstract]

Zhang, M. (2007) "Scaffold proteins as dynamic switches." Nat. Chem. Biol. 3, 756-757
[Abstract]

Wu, H, Feng, W., Chen, J., Chan, L.-N., Huang, S., and Zhang, M. (2007) "PDZ Domains of Par-3 as Potential Phosphoinositide Signaling Integrators." Mol Cell. 28, 886-898
[Abstract]

Pan, L. F., Wu, H., Shen, C., Shi, Y., Jin, W., Xia, J., and Zhang, M. (2007) "Clustering and synaptic targeting of PICK1 requires direct interaction between the PDZ domain and lipid membranes." EMBO J. 26, 4576-4587
[Abstract]

Olsen, O., Funke, L., Long, J.F., Fukata, M., Kazuta, T., Trinidad, J. C., Moore, K. A., Misawa, H., Welling, P. A., Burlingame, A. L., and Zhang, M. and Bredt, D. S.(2007) "Renal defects associated with improper polarization of the CRB and DLG polarity complexes in MALS-3 knockout mice." J. Cell Biol. 179, 151-164
[Abstract]