Cerebral Cavernous Malformations (CCM) is a neurovascular disease affecting up to 0.5% of the population. CCM are mulberry-like lesions found primarily in blood capillaries of the brain that are thought to be the result of junctional defects between endothelial cells lining the capillaries. This causes blood to leak into the brains of CCM patients and can cause symptoms that range from headaches and seizures to hemorrhagic stroke. Unfortunately, there are currently no pharmacological treatments for this disease, leaving invasive neurosurgery the sole treatment option.

Familial CCM follows an autosomal dominant inheritance pattern caused by loss-of-function mutations in one of three genes: CCM1/KRIT-1, CCM2/Malcavernin and CCM3/PDCD10. To study the biological functions of these genes, which encode three different scaffold proteins, we use the nematode worm Caenorhabditis elegans as an in vivo model system. Our work has revealed mechanistic insight into how the CCM1 and CCM3 proteins regulate cross-tissue signalling and vascular integrity.

Evelyn (PhD candidate) is interested in how the Myotonic dystrophy-Related, Cdc42-binding Kinase homologue, mrck-1, regulates excretory canal elongation and integrity. In a previous screen we uncovered mrck-1 as a CCM-related gene (Lant et al., 2015) that causes similar canal truncations when mutated as ccm-3. Evelyn is determining if mrck-1 functions downstream of ccm-3, or if it acts in a separate pathway, using classic epistasis analysis and engineering various mutants and reporters by CRISPR gene editing technology.