Project Reference: ICS27-PHA-DB1

Project title: How does mechanosensitivity shape neuro-stromal interactions in the endometrium?

Project outline

Pain sensing nerves or nociceptors are critical for the detection of injury, promoting withdrawal reflexes in addition to local effector responses through neurogenic release of neuropeptides highlighting the bidirectional nature of nociceptor signalling. 

Although much progress has been made in our understanding of how mechanical stimuli are transduced by nociceptors in somatic tissue via ion channels such TRPA1 or Piezo 2, our knowledge of how mechanical stimulus is transduced in visceral organs such as the uterus is still far from clear despite mechanosensitivity being the relevant stimulus for pain in pelvic organs and therefore clinically relevant to conditions such as endometriosis. One notable difference is the duration of stimulus as unlike somatic pain where exposure to noxious stimuli is often attenuated by nociceptor triggered withdrawal reflexes, visceral nociceptors are exposed to prolonged mechanical stimuli which are typically inescapable (for example during contraction of smooth muscle).  As such we would like to investigate the contribution of mechanosensitive G protein coupled receptors (GPCRs) to visceral nociceptor activation due to their ability to transduce external stimuli and maintain intracellular signalling over extended periods of time.  Furthermore, we would also like to investigate the contribution of neuro-stromal interactions to visceral nociceptor mechanosensitivity as we believe the prolonged activation of visceral nociceptors by mechanical events in the viscera facilitates greater neurogenic signalling with the surrounding tissue. 

To explore this, we will a) study the contribution of GPCRs to mechanical stimulation of visceral nociceptors by examining behaviour and utilising imaging and electrophysiological techniques, and b) examine the impact of neurogenic signalling on cellular function using tissue, organoid and co-culture models of endometrial neuro-stromal interactions. 

Principal Supervisor

Dr David Bulmer

Email address: dcb53@cam.ac.uk

Department / Partner Institute: Pharmacology

Website: https://www.phar.cam.ac.uk/research/bulmer

Industrial Partner

Cyclana Bio

BBSRC strategic theme

Understanding the rules of life