Homologous recombination proteins are associated with centrosomes and are required for mitotic stability.

In response to DNA damage, cells need robust repair mechanisms to complete the cell cycle successfully. Severe forms of DNA damage are repaired by homologous recombination (HR), in which the XRCC2 protein plays a vital role. Cells deficient in XRCC2 also show disruption of the centrosome, a key component of the mitotic apparatus.

Gelsolin plays a role in the actin polymerization complex of hair cell stereocilia.

A complex of proteins scaffolded by the PDZ protein, whirlin, reside at the stereocilia tip and are critical for stereocilia development and elongation. We have shown that in outer hair cells (OHCs) whirlin is part of a larger complex involving the MAGUK protein, p55, and protein 4.1R.

A mutation in the mitochondrial fission gene Dnm1l leads to cardiomyopathy.

Mutations in a number of genes have been linked to inherited dilated cardiomyopathy (DCM). However, such mutations account for only a small proportion of the clinical cases emphasising the need for alternative discovery approaches to uncovering novel pathogenic mutations in hitherto unidentified pathways. Accordingly, as part of a large-scale N-ethyl-N-nitrosourea mutagenesis screen, we identified a mouse mutant, Python, which develops DCM.

The PCP genes Celsr1 and Vangl2 are required for normal lung branching morphogenesis.

The lungs are generated by branching morphogenesis as a result of reciprocal signalling interactions between the epithelium and mesenchyme during development. Mutations that disrupt formation of either the correct number or shape of epithelial branches affect lung function. This, in turn, can lead to congenital abnormalities such as cystadenomatoid malformations, pulmonary hypertension or lung hypoplasia.

Whirlin complexes with p55 at the stereocilia tip during hair cell development.

Hearing in mammals depends upon the proper development of actin-filled stereocilia at the hair cell surface in the inner ear. Whirlin, a PDZ domain-containing protein, is expressed at stereocilia tips and, by virtue of mutations in the whirlin gene, is known to play a key role in stereocilia development. We show that whirlin interacts with the membrane-associated guanylate kinase (MAGUK) protein, erythrocyte protein p55 (p55).

Mutant analysis reveals whirlin as a dynamic organizer in the growing hair cell stereocilium.

Little is known of the molecular processes that lead to the growth of stereocilia on the surface of hair cells in the inner ear. The PDZ protein whirlin is known, by virtue of the whirler mutation, to be involved in the process of stereocilia elongation and actin polymerization in the sensory hair cells of mammals. We have investigated the function of whirlin and its putative interacting partner, myosin XVa, in the stereocilium using relevant mice mutants.

Filamin C interacts with the muscular dystrophy KY protein and is abnormally distributed in mouse KY deficient muscle fibres.

The KY protein has been implicated in a neuromuscular dystrophy in the mouse, but its role in muscle function remains unclear. Here, we show that KY interacts with several sarcomeric cytoskeletal proteins including, amongst others, filamin C and the slow isoform of the myosin-binding protein C. These interactions were confirmed in vitro and because of its central role in skeletal muscle disease, characterized in more detail for filamin C.