Roly Megaw is awarded a Wellcome Clinical Research Career Development Fellowship!

We are thrilled to announce that Roly has been awarded this prestigious fellowship from Wellcome, which enables clinically active healthcare professionals to continue their research at postdoctoral level and develop scientific independence.

As a clinical ophthalmologist, Roly’s aim is to better understand the process of photoreceptor disc formation and interrogate how its dysregulation leads to the development of Retinitis Pigmentosa (RP), an inherited, retinal dystrophy that affects 1 in 3000 people worldwide. In this fellowship, he will explore how the Retinitis Pigmentosa GTPase Regulator (RPGR), mutations in which cause 15% of RP, can act as an assembly platform that recruits actin binding proteins (ABPs) to promote membrane curvature at the photoreceptor’s distal connecting cilium, resulting in disc formation.

RP is a disease of the human photoreceptor, of which the light-sensitive ‘outer segment’ is a highly specialised primary cilium, which is the focus of our work in the Mill lab. Primary cilia are signalling organelles present on vertebrate cells whose dysfunction is associated with a spectrum of disorders, the ‘ciliopathies’. A key feature of many systemic ciliopathies is RP. Photoreceptors contain the most elaborate primary cilia in our body, comprising a ‘connecting cilium’, out of which emerges an expanse of folded membrane discs packed with the photosensitive pigment rhodopsin. These discs, constituting the photoreceptor’s outer segment, continually turn over in a highly dynamic process. Molecular mechanisms governing disc morphogenesis remain poorly understood.

Roly will focus on how regulation of actin by RPGR controls disc formation- with a little help from fantastic collaborators Laura Machevsky (Beatson, Glasgow, UK), Theodore Wensel (Baylor College, Houston, USA) and Vadim Arshavsky (Duke University, Durham, USA).