In the Netherlands, approximately 1 million children (0-25 years) have a chronic disease. Above and beyond the ever-present challenges of growing up with an illness, these children have 40% chance to develop psychological problems, including depression, anxiety and loneliness. Throughout their life, this translates into decreased well-being and reduced social participation and generates additional costs for society. Early prevention of psychological problems is thus key to break this vicious cycle. Therefore, eHealth applications are promising. However, scientific knowledge is missing and validated tools are not yet available for this group and involved health care professionals. Our mission is to make scientifically validated eHealth tools that allow personalized and trans-diagnostic prevention of psychological problems widely available for this highly vulnerable group of chronically ill children and future adults, through an accessible, user-friendly, safe, and sustainable platform. To succeed in this mission, we present an iterative learning cycle approach in two four-year phases during which we gather the insights, and develop, evaluate, and implement the much needed eHealth tools: I. Development: Distil and validate the theoretical and game-design factors that make eHealth effective for chronically ill children. II. Evaluation: Evaluate trans-diagnostic and personalized eHealth tools for chronically ill children, using and developing state-of-the-art methods. III. Implementation: Study and remove the barriers that currently hinder implementation and uptake, and threaten availability of eHealth applications for chronically ill children. Our eHealth junior consortium includes (applied) researchers, pediatricians, psychiatrists, psychologists, patient organizations, knowledge centers, game designers, industrial designers, insurance companies, and business professionals. We will collaborate with the end-users (children, families, and professionals) in order to achieve both international scientific breakthroughs and optimal clinical and societal impact. Knowledge utilization is a crucial part of our project.

-

Gene expression drives essential cellular processes in multicellular organisms. The BAF chromatin remodeling complexes are a cluster of proteins that control gene expression in our genome. Mutations in BAF cause many diseases including >20% of human cancer cases. Here, we aim to deconstruct gene regulatory process of two important BAF subunits called SMARCB1 and BRD9. The two subunits are often mutated or amplified in human cancers and neurodevelopmental diseases. Deep understanding the regulatory functions of the two subunits will shed light on pathogenic roles of the mutations in these diseases.

Enteric viruses from sewage overflows into water catchments threaten public health through food production and recreational activities. Despite wastewater treatment and water quality monitoring, viral contamination of food still occurs in Europe, impacting consumers health and food producers economically. Shellfish filter large amounts of water, making norovirus contamination a major cause of foodborne outbreaks. While rainfall plays a role, the impact of extreme weather events remains unclear. This project aims to ensure safe and sustainable water use, particularly in shellfish production, by improving understanding of viral contamination and developing an early-warning tool to mitigate risks during extreme hydroclimatic events.

Attention-deficit/hyperactivity disorder (ADHD) is a neurobehavioral developmental disorder, affecting 3-7% of children. It is characterized by a persistent pattern of impulsiveness and inattention, with or without hyperactivity. Structural imaging studies have demonstrated regional brain changes, including (sub)cortical grey matter volume reductions in children with ADHD. Twin studies indicate that ADHD is highly heritable. However, genome-wide-association studies have failed to reliably identify genetic variants that explain even a small part of the genetic risk. Most likely, the combination of many genetic variants explains the vulnerability to ADHD. We propose a novel approach that utilizes functional genomic information to group genes into ?functional gene networks? (FGNs). We will subsequently test for the association of FGNs with ADHD symptoms and a clinical diagnosis of ADHD, in a large population-based cohort (n=3600) and a clinical cohort (N=300 cases). In addition, we will investigate how these FGNs relate to ADHD by conducting functional genetic experiments as well as brain imaging experiments. Large international replication cohorts are available. This project integrates expertise from child psychiatry, functional genomics and brain imaging. We propose to link functional gene networks to brain morphology, and directly relate any patterns observed to the morphological and clinical correlates of ADHD, aiming to formulate an integrative theory of the genetically mediated neural substrates of ADHD.