Publications and pre-prints
Below are some of our selected publications and pre-prints, for a full list please click here.
Diverse lateral gating mechanisms in human rhomboids
In collaboration with the Corey lab, we find that human rhomboids have unexpected diversity in substrate engagement mechanisms. This is most notable with the orphans RHBDL1 and RHBDL3, which have unusually narrow lateral gates that require substantially higher energy to open (currently available as a pre-print on bioRxiv).
TMD plasticity controls PINK1 import and cleavage
In collaboration with the Collinson and Corey labs in Bristol, we discovered that structural plasticity in the TMD of PINK1, a kinase mutated in Parkinson’s disease, underpins whether it is cleaved by the rhomboid PARL, or enters the matrix of mitochondria.
RHBDL2 and Orai1
We performed a bioinformatics-led cell biological screen to identify new substrates for the rhomboid protease RHBDL2. It led to the discovery that RHBDL2 recognises a calcium channel called Orai1 when it is inappropriately activated, and cleaves it to turn it off and thereby control downstream signalling.
E-cadherin cleavage and tumorigenesis
We noted that during oncogene-driven single cell extrusion from a wild type epithelial monolayer, the adherens junction protein E-cadherin was cleaved. This led us to generate an artificially cleavable form of E-cadherin and show that its cleavage is sufficient to drive epithelial extrusion.