Laboratory of Neuroglycobiology and Sensation

Lab head: Michelle B. Gerke
Location: Anderson Stuart Building, Camperdown Campus

Research in this laboratory focuses on primary sensory neurons. These are the first neurons in sensory pathways, having receptors in peripheral tissues (skin, muscle, viscera), cell bodies in the dorsal root ganglia and axons which terminate in the spinal cord.

It has been shown that, along with their expression of specific channels and receptors, primary sensory neurons responsible for detecting different stimuli can be distinguished on the basis of the constellation of sugars expressed in their cell membrane (neuroglycobiology). Identification of sensory neurons on the basis of their unique 'sugar code' allows for the focused study of those populations which are responsible for mediating particular sensations under healthy conditions and also provides an avenue for assessing their specific involvement in sensory dysfunctions associated with particular disease states.

To date, most of the research done by members of this lab has focused on identifying and studying a population of small diameter primary sensory neurons which express the sugar alpha-D-galactose in their cell membrane. We have provided evidence that these neurons, which can be distinguished from other primary sensory neurons on the basis that they selectively bind the plant lectin Bandeiraea simplicifolia I isolectin B4 (IB4), are present in the dorsal root ganglia and spinal cord of a variety of mammalian species, primarily innervate the skin (as opposed to muscle and viscera) and generally display the anatomical, ultrastructural and electrophysiological features of neurons responsible for the initial detection and transmission of noxious / painful stimuli (also known as nociceptors). Thus, the identification and specific study of primary sensory neurons which express alpha-D-galactose (those that bind IB4) can provide a thorough understanding of the morphology, molecular phenotype and physiology of nociceptors in general, and can be applied to enhance our knowledge regarding the transmission of painful stimuli from the periphery to the spinal cord in both healthy and diseased states.

 

Current research in this laboratory applies the ability to distinguish and label nociceptors to investigations aimed at enhancing our understanding of:

The anatomical and phenotypic changes associated with chronic pain.

The sensory innervation patterns of peripheral tissues involved in common pain conditions such as headache, muscle and joint pain.

The anatomical basis of referred pain. 

 

The Laboratory of Neuroglycobiology and Sensation investigates the role and contribution of nociceptors in the development and maintenance of chronic pain conditions which occur after nerve injury. The ultimate goal of this research is to unravel the contributions that nociceptors make to the development of sensory dysfunctions associated with nerve injury pain with a view to identifying new therapeutic targets towards which neuron-specific pain treatments might be aimed.

Lab members: Michelle Gerke (head) Gagandeep Kaur (M.Phil) Ashneeta Kumar (M.Phil) Jose Filipe Gonsalves (Hons) Lena Lujing Liu (RA) Tim Zhang (GMP / RA)

Unravelling the contributions of peripheral nociceptors and central glial cells to the development of chronic neuropathic pain states

Primary supervisor: Michelle Gerke-Duncan

Research in this lab is currently focussing on the contribution of both peripheral nociceptors and central glial cells to the development of chronic neuropathic pain states in an attempt to elucidate a link between these cells types and the perpetuation of sensory abnormalities. Neuropathic pain is a persistent pain state that arises from damage to the nervous system and is usually accompanied by sensory abnormalities including hyperalgesia and allodynia. The animal model used in these projects has been shown to closely reflect the neuropathic pain state experienced by humans.

Whilst the main project on offer is made up of a number of puzzle pieces, our primary focus to date has been assessing the effect of nerve damage on the expression of the sugar code of nociceptors and the time course of microglial infiltration into the area of the superficial dorsal horn innervated by the injured nerve. Recent work from our laboratory has shown that alterations in nociceptors and microglia occur at the same anatomical location within the spinal cord of animals showing sensory dysfunction after nerve injury. The next step is to resolve whether or not glial infiltration is actually triggered by the altered nociceptors and to investigate whether the prevention of glial triggering effectively stops pain perpetuation or sensory dysfunction.

Our current approach to unravelling the neuron glial-link is to exploit the neuronal sugar code and use targeted cell death as a means to remove specific cell types from the neuropathic pain equation. The rationale here is that removal of particular cell types from the equation will allow us to assess the role that particular cell types play in neuropathic pain development and perpetuation. These projects are also pointed towards assessing the efficacy of such targeted cell death as a selective and long lasting pain therapy.

Results from these projects will help build on our current knowledge of the mechanisms underlying chronic pain perpetuation whilst giving students an opportunity to gain research skills and a more through understanding of some of the cellular players in pain transmission and perpetuation. Students will gain skills and experience in animal handling, sensory and behavioural testing, surgery, tissue collection, histological and immunostaining techniques along with fluorescence microscopy and image analysis.


Discipline: Anatomy & Histology
Keywords: Neurosciences, Pain and symptom management
Contact: Email Michelle Gerke-Duncan