We wish to improve clinical care for cardiovascular patients by considering and integrating multi-modal data from omics, imaging and electronic healthcare data using computational tools from genetics, machine learning and artificial intelligence. For example, we aim to use human genetics to identify viable protein drug targets to increase the yield of drug development programs.

A mutation in one copy of the KCNQ1 gene causes cardiac arrhythmias that can suddenly kill the carrier. It is unclear why in family members carrying exactly the same mutation these cardiac arrhythmias vary greatly. We propose that this variation is caused by differences in the balance in expression between the healthy and mutated allele, which can be caused by variants in the 3? UTR. Indeed, we found that 50% of the family members carried variants in the 3?UTR of KCNQ1 that suppress translation. When these variants reside on the mutated allele, this suppresses formation of the mutated protein and decreases cardiac arrhythmias. This novel mechanism largely explains the variation in disease severity.4 We further show that these variants create binding sites allowing microRNA-378 to suppress that specific allele. We aim to study how microRNA-378 alters allelic balance and electrophysiological properties in human iPS-cell derived cardiomyocytes obtained from mutation carriers who also carry the above 3?UTR variants. We anticipate to test whether inhibition of microRNA-378 can shift the allelic balance away from the mutated protein. If confirmed, this opens the exciting possibility to inhibit microRNA-378 as a novel therapy tailored at individual genomic variants to shift the allelic balance to the normal protein. Keywords: long QT syndrome, microRNA-378, induced pluripotent stem cells, allele-specific effects, single nucleotide polymorphisms

In the last decade, computer-mediated communication (CMC) has grown explosively as a means of communication. The popularity of different digital communication technologies―from text messaging (texting, SMS) and instant messaging (IMing) to Twitter, Whatsapp, and social networking sites such as Facebook and Hyves―has increased rapidly, also among children, adolescents, and young adults. Because the language used in CMC can deviate from the conventional norms of spelling, grammar, and punctuation, this has raised concerns among adults, teachers, and the media that CMC may have a detrimental effect on traditional literacy: they are afraid it may degrade youngsters? reading, writing, or spelling skills. Linguists, on the other hand, point out what they see as positive aspects of using CMC, such as increased exposure to text, increased motivation to read and write, and increased phonological and metalinguistic awareness. Previous empirical studies into the effects of CMC on literacy exhibit a mixed pattern of results. The proposed project aims to bring order into this chaos of opinions and findings by further investigating the impact of CMC on literacy in four subprojects: theoretical research, corpus research, correlational research, and experimental research. The project will scrutinize register differences between the informal ?texting system? used in CMC and the more formal ?school system? used at school, it will investigate whether interference occurs between these two language systems, and it will study the effect of factors such as youngsters? educational level and age group on this interference. Furthermore, this project will overcome various limitations of previous studies: it will include Dutch participants, it will consider not just texting and IMing but also other forms of CMC, it will reconceptualize the notion of literacy in view of the technological developments of this digital age, and it will explore the causal relationship between CMC and literacy. The Centre for Language Studies at Radboud University Nijmegen would be happy to facilitate the empirical research. The proposed PhD-candidate is enthusiastic and eager to tackle the challenges presented by this project, so that she can finally apply the knowledge she has gained in the many theoretical and applied linguistics courses she has completed during her Bachelor?s studies, her first Master?s studies, and her current Research Master?s programme―all of which makes her the right person for this project.