Project proposal details

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Project title
Evolutionary genomic analysis of Transient Receptor Potential Vanilloid 1 (TRPV1) in human and non-human populations: Unlocking the evolutionary origin of burn pain
Contact name
Matteo Fumagalli
Project based at
Silwood Park (Imperial)
Project description
Early human ancestral development of fire as a tool emerged relatively recently in the evolutionary past. Since mastery of fire, many positive adaptations emerged as homo-sapiens achieved dominance over the globe. The survival benefit from utilisation of fire as a tool were huge. As a result, fire use increased dramatically as did the associated lifetime risk of burn injury, a previously rare injury type. This may have resulted in a maladaptive response to burn injury when encountered in the more modern era, as inflammatory and immune systems evolved in the millennia prior to frequent use of fire. The benefits of fire use are clear for early humans, but they came at a cost of burn injury. As a consequence high selective pressures exist for new adaptations to avoid serious burn injury in the context of this relatively new, and serious tissue injury type.

Burn pain responses may be a positive adaptation for this reason. Transient Receptor Potential Vanilloid 1(TRPV1) is a receptor on skin nociceptors in humans and many other species. It is strongly implicated in the generation of skin sensitivity to heat following a burn injury. A proposed adaptive explanation is to prevent further burning following an initial burn and associated worse injury by inducing a strong heat avoidance behaviour. It is hypothesised that TRVP1 and the genes encoding for this protein (and associated epigenetics) are strongly selected for in modern humans. It is proposed to be greater than in non-human mammals where burn injury is a less common threat, and greater than non-burn nociception such as that associated with PIEZO channel mechanoreceptors, which would have been under a similar selective pressure for many millennia prior to the common use of fire.

In this project, the student will perform phylogenetic analyses of TRPV1 and test for adaptation in the human lineage.

This will be a bioinformatics project with co-supervision from Dr Josh Cuddihy and Dr Istvan Nagy, Faculty of Medicine, Department of Surgery & Cancer, Chelsea and Westminster Hospital.
Additional requirements
Good attitude to programming in bash and R/python.
Available support
Additional training can be provided.
Selection and eligibility
This project is remote.
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