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Assessment of excitability of Human pain neurons pain neurons using a novel calcium imaging assay

  • Full or part time
  • Application Deadline
    Wednesday, January 23, 2019
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Pain is an important warning system to guard against tissue damage. Pathological pain, however, has no warning value and has huge economical, social and personal costs on society. Sensory neurons of the Dorsal Root Ganglia (DRG) detect painful stimuli and transmit sensory information to regions of the CNS that perceive pain. Inflammation and nerve injury sensitise DRG neurons and result in decreased pain thresholds and increased pain. Pain scientists study DRG neurons in order to delineate pain signalling in order to discover new analgesic drug targets. DRG contain a heterogeneous population of neurons with distinct functional and histochemical properties which can be identified by their dependency on trophic factors, ion channel expression, size, myelination and stimulus responses. Primary cultures of DRG neurons are used to study their excitability and functional properties and how they are changed by tissue damage. In addition, primary cultures of DRG neurons are used in pharmaceutical research to screen for and test potential analgesic compounds.

Reliable, efficient and informative functional assays are important for drug discovery and testing. We have recently developed an unbiased, efficient and high content assay to assess the excitability of cultured DRG neurons. The assay is based on using Veratirdine to activate DRG neurons and calcium imaging to record their response. Veratridine is a VGSC channel opener that is used as an “agonist” to study VGSCs in sensory neurons. We have found that Veratridine produces distinct response-profiles in cultured sensory neurons that map to known functional neuronal subtypes. These response-profiles distinguish between nociceptive neurons (pain sensing) and non-nociceptors. Our functional assay has several advantages over currently used methods. Firstly, it is more efficient than patch-clamping neurons. We typically obtain recordings from 200-500 neurons per day compared to 10 using patch-clamping. Secondly, our assay uses a single agent (Veratridine) to activate all types of neurons. Thirdly, our assay uses cultured sensory neurons which are more physiologically relevant than heterologous expression system in e.g. the HEK cell line. As a result, we are observing effects of drugs that does not show an effect on HEK cell line. We also observe the existence of a silent population of neurons (not activated by Veratridine) as was described by calcium imaging of DRG neurons in vivo. Fourthly, our assay generates a wealth of data that can be used to accurately assess changes in the excitability of DRG neurons.
This project aims to characterise the response profiles in Human sensory neurons to those obtained from the widely used rodent neurons.

Science Graduate School
As a PhD student in one of the science departments at the University of Sheffield, you’ll be part of the Science Graduate School. You’ll get access to training opportunities designed to support your career development by helping you gain professional skills that are essential in all areas of science. You’ll be able to learn how to recognise good research and research behaviour, improve your communication abilities and experience the breadth of technologies that are used in academia, industry and many related careers. Visit http://www.sheffield.ac.uk/sgs to learn more.

Funding Notes

Please note that we have a number of fee scholarships available, please get into contact with Dr. Kai Erdmann in case you would like to know more: View Website

Entry requirements
First class or upper second 2(i) in a relevant subject. To formally apply for a PhD, you must complete the University's application form using the following link: View Website

*All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information*.

References

Reference: https://www.ncbi.nlm.nih.gov/pubmed/28338073

How good is research at University of Sheffield in Biological Sciences?

FTE Category A staff submitted: 44.90

Research output data provided by the Research Excellence Framework (REF)

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