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Norwich Research Park Featured PhD Programmes
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Neuromuscular junction development and disease

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

About This PhD Project

Project Description

Synapses are specialized cell membrane domains that facilitate neuronal communication in the intricate nervous system. These synaptic specializations develop in response to molecular interactions between pre- and postsynaptic cells. A major goal of current research in developmental neuroscience is to elucidate the mechanisms underlying how synapses are assembled. The nerve-muscle synapse, neuromuscular junction (NMJ), which controls all muscle movements, has been considered as the best model for the study of synaptogenesis due to its large size, simplicity and accessibility. When neurons and muscle cells are cultured together, functional NMJs are formed spontaneously. The structure and physiology of mature vertebrate NMJs are well understood. Currently, our laboratory specifically focuses on the signal transduction and cytoskeletal mechanisms underlying synapse development, disease, and regeneration.

Three major areas are being pursued in our lab:

1. Matrix metalloproteinases in synaptic development
2. Cytoskeletal dynamics in motor neuron development and disease
3. Neurotrophic signaling in muscle physiology and disease

Using the simple and elegant Xenopus primary culture system, a variety of techniques, including live-cell time-lapse fluorescence microscopy, super-resolution microscopy, molecular biology, immunocytochemistry, and Western blotting will be applied to these experimental systems to gain understanding to the cellular and molecular mechanism of synaptic development. Our goal is to not only gain a mechanistic understanding of the molecular and cellular aspects of neuronal structure and function, but also provide insights into the cellular basis for neurological disorders.

References

Yang X, Brobst D, Chan WS, Tse MC*, Herlea-Pana O, Ahuja P, Bi X, Zaw AM, Kwong ZS, Jia W, Zhang Z, Zhang N, Chow SK, Cheung WH, Louie JC, Griffin TM, Nong W, Hui JH, Du G, Noh HL, Saengnipanthkul S, Chow BK, Kim J, Lee CW# and Chan CB (2019) Muscle generated brain-derived neurotrophic factor is a sex-dimorphic myokine that controls metabolic flexibility. Science Signaling 12(594): eaau1468.

Yeo HL*, Lim JY*, Fukami Y, Yuki N, and Lee CW# (2015) Using Xenopus tissue cultures for the study of myasthenia gravis pathogenesis. Developmental Biology 408(2): 244-51.

Lee CW, Vitriol EA, Shim S, Wise AL, Velayutham RP and Zheng JQ (2013) Dynamic localization of G-actin during membrane protrusion in neuronal motility. Current Biology 23(12):1046-56. (2012 Impact factor: 9.49)

Gu J^, Lee CW^, Fan Y^, Komols D, Tang X, Sun C, Yu K, Hartzell HC, Chen G, Bamburg JR and Zheng JQ (2010) ADF/cofilin-mediated actin dynamics regulate AMPA receptor trafficking during synaptic plasticity. Nature Neuroscience 13(10):1208-15. (^ Co-first authors) (2009 Impact factor: 14.35)

Lee CW, Han J, Bamburg JR, Han L, Lynn R and Zheng JQ (2009) Regulation of acetylcholine receptor clustering by ADF/cofilin-directed vesicular trafficking. Nature Neuroscience 12(7):848-56. (2008 Impact factor: 14.16)

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