Genetic changes (mutations) in the gene Protocadherin-19 (PCDH19) - located on the X-chromosome - are associated with Epileptic Encephalopathy Early Infantile 9 (EIEE9), a rare genetic disease that causes early onset epilepsy and cognitive impairment in heterozygous females (females that carry a normal and a mutant copy of PCDH19). To date, little is known about how this phenomenon causes EIEE9, however the early onset of the disorder suggests a neurodevelopmental basis. Using genetically-altered mice, we have shown that Pcdh19 has a critical role in brain development by helping primordial brain cells called progenitors communicate with each other and transition into mature nerve cells, an event called neurogenesis. We also found that progenitors that express Pcdh19 and progenitors that do not express Pcdh19 produce significantly less and more nerve cells, respectively, but only in the developing brains of heterozygous female mice, which may be the underlying factor of EIEE9. To explore this further, we aim to discover the significant molecular pathways that Pcdh19 might be involved in to regulate neurogenesis using candidate and unbiased approaches. The results from this project will provide new insight into the roles of Pcdh19 during brain development and highlight potential targets for EIEE9 therapeutic intervention.

The Trust’s major directions for use of this Fund are as follows: 1. To assist the Institution in developing its research strategy across College’s and Schools 2. To encourage new inter-departmental synergies, cross-disciplinary collaborations, and inter-institutional initiatives 3. To add value to existing Wellcome Trust investments in the Institution. Strengthening Biomedical and Clinical SciencesCardiff University will build on successes of the first ISSF Award, widening the portfolio to encompass all the priority research areas in the College of Biomedical and Life Sciences (CBLS). We will build new links with relevant research in computing, physical sciences, humanities and social sciences and consolidate ties with partner Universities in the South West. CBLS, which includes all the Health-related Schools in the University, has recently completed a comprehensive review of its research portfolio and identified five Themes around which investment will be focused: Immunology, Infection & Inflammation; Mind, Brain & Neuroscience; Cancer; Public Health & Integrative Biosystems. The ISSF Award will impact in all these areas. Previous ISSF success 2013The Award, with matched funding, supported new academic appointments, seven project grants, thirty-one seedcorn grants and eight mobility awards. Infrastructure was supported through substantial spend on new equipment. Public engagement was supported through contributions to high profile local events and stand-alone meetings.