Investigation into the molecular function and pain profile of genetic variation in the irritant sensor TRPA1

Even with healthy aging, pain is an increasingly prevalent symptom, with a large impact on quality of life. Therefore the effective prediction, prevention and treatment of chronic pain will be a significant step towards lifelong health. Understanding the biological mechanisms by which we feel pain is vital to creating new analgesic medicines that are both effective and non-addictive.
TRPA1 is a plasma membrane ion channel which is a sensor molecule on neurons that detect threats (nociceptors), including heat, cold and inflammatory signals / free radicals. For this reason TRPA1 is of interest as a target for analgesics and also as a gene potentially modulating susceptibility to pain Therefore the study of both common and rare (disease-associated) genetic variation is of considerable interest. At Eli Lilly the student will carry out in-vitro assays to ascertain how cells carrying different human TRPA1 variants respond to thermal stimuli, sensitising chemicals and pharmacological compounds. They will also use state-of the-art high throughput imaging systems to ascertain plasma membrane trafficking of the ion channels, and their formation into functional complexes.
The UK Biobank is an unparalleled resource following the health and wellbeing of 500,000 individuals. Data releases expected in 2019 include the first 50,000 exomes and detailed information on pain symptoms. The student will data mine this resource for associations between TRP-channel genotypes and pain phenotypes, cross-linking data from hospital and GP records, self-report, imaging and biomarkers to create a detailed profile linking variants in nociceptive channels with population pain phenotypes.