Guthrie Lab

Characterising the alpha2-chimaerin 'interactome'

Alpha2-chimaerin (α2-chn) is a multi-domain protein, mutations in which lead to eye movement disorders in humans. There are some known α2-chn binding partners, but many more remain to be discovered. We propose that differential interactions with binding partners by wild-type and mutant forms of α2-chn might mechanistically underlie DRS.

In this project we have used quantitative proteomics with liquid chromatography and tandem mass spectrometry to identify novel components of the α2-chn signalling ‘module’. We are characterising the effects of human α2-chn mutations on the composition and function of the signalling module, giving insights into the causation of DRS. To determine the functional role of the candidate chimaerin-interacting proteins we are using in vivo gain- and loss-of function approaches in the zebrafish. In this way we will identify the signalling module components whose misregulation leads to Duane Retraction Syndrome and the mechanisms involved.