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Extracellular matrix remodeling in neuromuscular synapse development


School of Biomedical Sciences

Applications accepted all year round Funded PhD Project (Students Worldwide)

About the Project

Motor neurons, skeletal muscles, and perisynaptic Schwann cells interact with extracellular matrix (ECM) to form the tetrapartite synapse in the peripheral nervous system. Dynamic remodeling of ECM composition is essential to diversify its functions for distinct cellular processes during neuromuscular junction (NMJ) development. The proteolytic regulation of ECM proteins is mediated by secreted and membrane-type matrix metalloproteinases (MMPs), in axonal growth and NMJ development. In our lab, we primarily use Xenopus primary culture system and a variety of techniques, including live-cell time-lapse fluorescence microscopy, super-resolution microscopy, molecular biology, immunocytochemistry, electrophysiology, and Western blotting to investigate the cellular and molecular mechanism of synaptic development. Our goal is to not only gain a mechanistic understanding of the regulatory functions of MMP-mediated ECM remodeling in axonal growth and NMJ development, but also provide insights into the pathophysiological mechanisms of MMP-mediated proteolytic degradation in neuromuscular disorders.

Faculty information, funding opportunities and application deadlines: https://www.findaphd.com/phds/program/biomedical-research-hku-li-ka-shing-faculty-of-medicine/?i586p4119

References

Chan ZC, Kwan HR, Wong YS, Jiang Z, Zhou Z, Tam KW, Chan YS, Chan CB and Lee CW* (2020). Site-directed MT1-MMP trafficking and surface insertion regulate AChR clustering and remodeling at developing NMJs. eLife 9: e54379.

Oentaryo MJ, Tse AC, and Lee CW* (2020) Neuronal MT1-MMP mediates ECM clearance and Lrp4 cleavage for agrin deposition and signaling in presynaptic development. Journal of Cell Science 133: jcs246710.

Chan ZC, Oentaryo MJ and Lee CW* (2020). MMP-mediated modulation of ECM environment during axonal growth and NMJ development. Neuroscience Letters 722: 134822.

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