Functional characterisation of primary sensory neurons derived from adult human dorsal root ganglia

Supervisors: Gareth B Miles, Gayle Doherty

Project Description:
Promising pain therapies developed in animal models have recently failed in clinical trials, likely due to differences between animal and human sensory neurons. There is therefore a critical need for the development, validation and characterisation of human cell-based models in which to study pain processing. Knowledge gained from such models and their future use in pain-related drug discovery and design could lead to enormous societal benefits. We have recently contributed to the development of techniques for acquiring and culturing human dorsal root ganglion (DRG) neurons. As part of this project we have already demonstrated that primary human DRG neurons can be grown successfully in culture and utilised for functional studies, such as whole-cell patch-clamp electrophysiology to interrogate action potential output as well as ion channel and receptor expression. However, there remains a relative lack of information regarding the functional properties of subclasses of human DRG neurons, including nociceptive pain-sensing neurons. It is therefore important to now conduct a thorough characterisation of functionally distinct populations of human DRG neurons, directly comparing properties of human cells with the wealth of knowledge regarding rodent DRG neurons. We propose to provide this important new information in the present project by utilising a combination of state-of-the-art electrophysiological (whole-cell patch-clamp) and live cell imaging techniques available at St Andrews and via collaboration with our industrial partner Metrion Biosciences. Data gained from the proposed study will provide novel insight into the processing of sensory signals in the human nervous system and demonstrate the utility of an important new human cell–based model system for the future development of novel pain therapeutics in collaboration with industrial partners.