Identifying novel mechano-receptors in the sensory nervous system

Project title

Identifying novel mechano-receptors in the sensory nervous system

Description

Project Background

How do mammals detect the harmful nature of blunt force, or sharp objects? How does the body defensively increase sensitivity of injured tissues, making otherwise innocuous movements and touch feel painful? And how, as an inevitable consequence of aging, does the latter process go wrong over time, creating burdensome chronic pain? The last question is especially pressing due to the massive toll it exerts on society.

To answer these questions, we must look at sensory nerves. These are cells that supply our organs (including the skin) with the ability to detect information about the physical and chemical nature of the outer and inner environments. They do so via protein molecules called mechano-receptors. In the past decade we have learned much about the identity of these proteins. A new class of receptors (Piezo) were identified. In sensory nerves, these are responsible for detecting light touch as well as the position of our limbs. The identity of other MA receptors, among them those that detect painful touch and increased mechanical sensitivity in response to injury, are still largely unknown. Uncovering the identity of these receptors is a challenging task that carries a high reward. Such a discovery would greatly expand our knowledge about tactile sensation, and present new targets for the development of better pain-relieving medication.

Research Overview

In this proposal we take on this challenge by applying a two-pronged approach, both converging on the desired outcome of finding these important receptors.

First, we will search the entire human genome to identify receptors that enable mechano-receptor function. This is made possible by a new platform technology, developed and validated in our lab, which harnesses the unique potential of evolution to efficiently screen the entire genome.

The second approach involves comparison of two very similar (near-identical) nerve cell populations, each involved in detecting mechanical cues, and one of which we have found to have unknown MA receptors at a much higher level. This comparison has allowed us to generate a list of high-probability candidates, which we will test here to identify the correct receptors in these nerves.

The combined use of these two approaches will enable us to successfully identify new MA receptor molecules, which will deliver important advances to the field of pain study.