Alison Lloyd Research Group

Cell growth and regeneration

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Intimate interactions between Schwann cells (blue) and axons (green).

Schwann cells are the main glial cells of the peripheral nervous system. Properties of these cells make them a powerful model system for studying two fundamental biological processes: (1) Cell growth (2) Cell regeneration. Using a combination of primary in vitro culture systems and in vivo mouse models we aim to study the molecular and cellular mechanisms underlying the homeostatic regulation of these processes and how they become deregulated in diseases such as cancer. These studies should identify novel pathways important in these processes and new targets for regenerative medicine and cancer therapeutics.

Cell growth

Homeostasis in the adult requires a balance of positive and negative regulatory stimuli to control cell size and cell number. Whether a cell divides, grows or dies depends both on the levels of extracellular signals and the intrinsic ability of a cell to respond to these signals. Cell growth (addition of volume/mass), as cell proliferation and survival, requires an instructive signal but the signalling pathways and cell biology underlying cell growth are relatively understudied. Moreover, the additional mass required for tumour formation, requires deregulated growth pathways as well as a loss of proliferative controls but how oncogenic changes effect cell growth control is poorly understood.
Growth is often thought of as a uniform process however, specific cells contain different amounts of protein, membranes and organelles and these can change in response to specific stimuli. How cell set their size, count their organelles and adapt these to changing environments remain key unanswered questions in cell biology.

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Enormous variation in cell size and organelle proportionality dependent on instructive extracellular signals.

Projects in the lab include the following

  • Identification of novel cell growth pathways
  • Regulation of organelle biogenesis
  • Cellular mechanisms underlying cell growth
  • Oncogenic regulation of cell growth

Cell regeneration

 

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Following nerve injury- cords of Schwann cells (green) stream in to the wound, taking regrowing axons (red) along with them

 

The peripheral nervous system is one of the few tissues in the mammalian adult, which is capable of extensive regeneration. This process is all the more remarkable, in that repair can reconnect and re-establish fully transected nerves – requiring both the production of new tissue to bridge the gap between the nerve stumps and the accurate direction of regrowing axons back to their targets. Schwann cells are known to play a pivotal role in this process. In the adult, these highly specialised cells are normally in a quiescent state, myelinating larger axons or bundling together groups of smaller axons. Upon injury however, they dedifferentiate en masse to a progenitor/stem-like state and the proliferation and organisation of these cells is known to be critical for the repair process. Schwann cell number and state is strictly controlled by the axon both during development and following repair. Imbalances in this tightly regulated system would be predicted to result in either degenerative disorders or hyperproliferative disorders such as cancer. Consistent with this view, Schwann cell tumours, especially neurofibromas, resemble an unrepaired wounded nerve, in that Schwann cells within the tumours are dedifferentiated and proliferate in the absence of axonal contact in a mixture of fibroblasts and inflammatory cells.

 

Projects in the lab include the following

  • Understanding the plasticity of the Schwann cell differentiation state
  • Schwann cell/axonal interactions during repair and cancer
  • Novel mouse models for studying tumour development in NF1
  • Role of the microenvironment in the repair process and cancer.

 

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The complex beauty of peripheral nerves