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Molecular and Cellular Mechanisms of Cold Signalling in Somatosensory Neurons

Principal Supervisor: Dr Xuming Zhang

Secondary Supervisor(s): Professor Mark Wall

University of Registration: University of Warwick

BBSRC Research Themes: Understanding the Rules of Life (Neuroscience and Behaviour)

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Deadline: 4 January, 2024


Project Outline

Detection of noxious cold in the environment is essential to animal survival by triggering beneficial protective and avoiding responses. However, abnormal cold sensation causes cold allodynia, a clinical symptom manifesting as painful responses to even a mild drop in temperatures. It is often seen in the patients with neuropathic pain. This PhD project aims to decipher the receptors and signalling molecules responsible for the sensation and transduction of cold signals in physiological and pathological conditions.

Noxious cold stimulus is first detected by somatosensory neurons in the nervous system. Behavioural evidence strongly supports that TRPA1 ion channels on sensory neurons play a role in this process. However, cellular analysis did not show a good correlation between the cold sensitivity of neurons and TRPA1 channels, suggesting that other ion channels and molecules are also required. To establish the role of TRPA1 channels and explore unknown molecules in noxious cold transduction, we will employ genetic approaches to ablate or inactivate TRPA1+ neurons. We will then determine cold responses of animals. At the cellular level, we will analyse changes in electrical properties of sensory neurons in response to cold and protein-protein interactions. Similar analyses will also be applied to cold transduction under neuropathic pain conditions. We want to know whether different mechanisms are employed during physiological and pathological cold transduction.

A combined methodology will be used including electrophysiology, cell culture, live cell imaging, histology, molecular biology, transgenic mice breeding and animal behaviours. You will be supported by senior scientists in a vibrant and stimulating environment.

References

  1. Khan S et al. IQGAP1 promotes chronic pain by regulating the trafficking and sensitization of TRPA1 channels. Brain 2023, 146(6), 2595-2611.
  2. Buijs TJ et al. The role of cold-sensitive ion channels in peripheral thermosensation. Front Cell Neurosci. 2020, 14: 262.

Techniques

Cell culture, electrophysiology, gene transfection, live cell imaging, histology, confocal imaging, molecular biology, transgenic mice breeding and animal behaviours