Most of us will experience low back pain at some point in our lives. When it becomes chronic, it is one of the most significant drivers of disability, estimated to affect 600 million people globally – almost as many people as live in the entire European Union.
The biological causes of back pain are not well understood. We would like you to help us solve some of the mystery surrounding the condition. Specifically, you will explore the hypothesis that substances within connective tissue cells are at the root of many back pains, especially those that are caused by particularly painful nerve entrapments, like sciatica.
For this project, you will receive training in a wide-range of transferrable laboratory and computational skills, including bioinformatic analysis of existing RNA sequencing data, fluorescence-activated cell sorting of surgically resected connective tissue from sciatica patients, and generation, maintenance and study of stem-cell derived sensory neurons. All of these are already established in your supervisors’ laboratories.
Your objectives will be to:
– use re-analysis of existing RNA sequencing datasets to generate a list of substances released from connective tissues in the back that are able to directly interact with pain-sensing neurons (Year 1).
– use fluorescence-activated cell sorting to isolate target connective tissue cell populations from surgically resected tissues from sciatica patients. You will then test whether these populations express your target substances at RNA and protein level (Years 1 & 2).
– obtain ethical permission for a larger-scale study correlating target cell types and ligands with the pain experienced by patients prior to surgery (Year 1 for ethics, Years 2-3 for the study itself).
– use target ligands and/or cell populations to test whether they cause hyper-excitability in stem-cell derived sensory neurons, i.e. show causally and mechanistically that they really are at the root cause of pain (Years 1-3).
