Elucidating the ion permeation and gating mechanisms of the TRPV and TRPA subfamilies of TRP cationic channel proteins.

The transient receptor potential (TRP) family of ion channels are expressed in a plethora of both
excitable and non-excitable tissues, and are a key constituent of sensory signalling. Of particular
interest are the TRPV and TRPA subfamilies of this superfamily, which represent novel drug targets
for analgesics or atopic dermatitis therapeutics. However, the molecular determinants of gating and
ion permeation through these channels have so far been largely elusive, despite being essential to
understand TRP function and guide drug design.
In the proposed project the mechanisms of gating and ion permeation through TRPV and TRPA
channels will be investigated primarily through computational electrophysiology and atomistic
molecular dynamics simulations. Furthermore, complimentary analysis will be performed using
structural bioinformatics, employing evolutionary conservation and human population variation data.
The combination of these methodologies is expected to yield new insight into the function of these
exciting pharmaceutical targets and their role in disease.
Project provides training in Quantitative & Interdisciplinary Skills