RESEARCH INTERESTS
We use human genetics and functional studies in cells and ciliate organisms to understand the molecular genetic basis of ciliopathies, with particular focus on the motile ciliopathies (primary ciliary dyskinesia) and skeletal ciliopathies (Jeune syndrome, short rib thoracic dysplasias). Human cilia and sperm play diverse roles essential to many aspects of normal development and ciliopathies are an expanding group of >20 genetic disorders. Motile cilia dysfunction arising from cilia gene mutations causes a chronic respiratory disease associated with organ asymmetry, infertility and rare neurological symptoms. Dysfunction of primary (sensory) cilia can affect many critical signalling pathways, causing a spectrum of developmental conditions e.g. skeletal dysplasia, retinal degeneration, cystic kidney disease. Mutations in cilia proteins thus underlie a spectrum of complex, multisystem syndromic disorders, that collectively affect more than 1 in 1,000 people.

Through patient sequencing we have determined gene mutations causing human ciliopathy conditions, revealing the cellular protein networks essential to ciliated airway epithelium differentiation and the motility of human sperm and cilia. These include mullticiliogenesis regulators, a chaperone-mediated network of dynein assembly factors and multiple dynein assembly and cilia transport proteins. To help improve disease understanding and guide future clinical management and interventions, we are part of a pan-Europe clinical programme to document all human variants causing motile ciliopathies and the genotype-phenotype correlations that determine how a patient’s underlying genetics affect their clinical disease expression. .

Ciliopathies are incurable disorders affecting all ages of people and from earliest life. We are now translating our biological advances into an improved understanding of disease for the benefit to the affected patients, and developing new genetic medicines to accurately treat ciliopathy patients according to their underlying gene defect. We are currently testing RNA based drugs that correct different classes of mutations causing motile ciliopathy disease.