Life leads to death, which is arguably the sole universal characteristic of life. The association between the rate of living and the rate of dying has fascinated biologists for a century, but the principal causes of ageing in humans and other organisms are still not resolved. Life span and rates of senescence vary distinctly, even between closely related species of similar size. Yet, for many organisms an intriguing relation between metabolic rate and lifespan is observed: when summed over lifetime, the metabolic rate per unit body mass is remarkably constant. This relation spans a wide range of organisms from yeast to elephant, and includes humans. Also within species, metabolism seems to be causally related with ageing, since caloric (or dietary) restriction typically enhances life expectancy. Despite intense research efforts, the nature of the relationship between metabolism and ageing remains enigmatic. By establishing a Systems Biology Centre called Energy Metabolism and Ageing (SBC-EMA), we will apply a systems biology approach to shed new light on metabolism, ageing, and their interaction. The metabolic rate of an organism is the result of the complex interplay of biochemical and physiological processes acting at various levels of organisation (mitochondria, cells, tissues, organs). Similarly, the physiological and molecular deterioration that characterizes ageing reflects the failure of networks of interacting cells, tissues and organs. Hence, by their very nature both metabolism and ageing require a systems biology approach in order to achieve a full understanding of their nature and their interaction. To unravel the complex relationship between energy metabolism and lifespan, SBC-EMA will combine large-scale data generation efforts with both data-driven top-down approaches and hypothesis-driven bottom-up approaches. In the first phase of its development, the Centre will focus on two model systems: the yeast Saccharomyces cerevisiae and mice Mus musculus. Metabolism and ageing in unicellular yeast and mice shows many similarities as well as differences, but the existence of a universal relation between metabolic rate and ageing suggests that key mechanisms underlying the ageing process are conserved from microorganisms to humans. We aim to discover these general mechanisms and this is an important motivation to study mouse and yeast next to each other. Yeast allows detailed investigations at the level of cells and organelles and they age rapidly. Moreover, a plethora of ?omics? information and techniques is already available, also within the University of Groningen, and metabolic and signalling pathways have been well characterised. Mice will be used to generate and test hypotheses involving intercellular and inter-organ relationships that are critical in higher organisms including humans. By applying similar manipulations (caloric restriction) in two model systems, we will simultaneously study intracellular (yeast) and higher-order (mice) processes in unprecedented detail with the aim to uncover the fundamental ageing processes shared by all life. This proposal is a joint research initiative of two faculties of the University of Groningen, the Faculty of Mathematics and the Natural Sciences (FMNS) and the Faculty of Medical Sciences (FMS). To achieve our ambitious goal, SBC-EMA brings together leading groups from both faculties, with expertise ranging from biochemistry, (molecular) biology, physiology and medicine to mathematics, statistics, bioinformatics and theoretical biology. The research theme of SBC-EMA builds on a rich history in both energetics and ageing research in both faculties. The University of Groningen has identified Healthy Ageing as one of its central research themes, and has founded the European Research Institute on the Biology of Ageing (ERIBA), which will focus on fundamental aspects of the biology of ageing. SBC-EMA will be physically and scientifically embedded within ERIBA together with other facilities like the Groningen Genomics Coordination Centre. By creating first-class infrastructure and by their recruitment policy, the University already demonstrates its commitment to systems biology. They also show a commitment to this proposal by providing 12 PhD student positions in addition to the positions requested in this proposal. SBC-EMA will be a vibrant Centre where scientists with diverse backgrounds will meet and collaborate on a daily basis to understand the fundamentals of ageing. Although research in SBC-EMA is predominantly fundamental, the topic of (healthy) ageing is of major societal relevance. Our research program on yeast and mice will therefore interact closely with Lifelines (and the complementary Systems Genetics endeavours), which will become the largest longitudinal population study in the Netherlands, involving more than 150,000 individuals. SBC-EMA will also have considerable scientific and educational outreach, by making data and results available to the scientific community, by developing user-friendly systems biology software, and by launching attractive systems biology courses for graduate and postgraduate students.

In popular Netflix series like Heartstopper, Ginny & Georgia, and Sex Education, reading is prominently featured. This project therefore investigates the potential these series offer for promoting literacy in educational contexts. To this end, a media-semiotic analysis of reading characters in high school series is conducted. Subsequently, relevant scenes from the analyzed material are presented to focus groups of teachers and students from secondary education. By closely combining cultural studies and education-oriented research, the project aims not only to push boundaries in the study of reading culture but also to provide implementable insights for literacy education.

The collection of big data, i.e. the integration of personalized databases on various dimensions, including demographic data, consumer preferences, and mobile phone numbers, has important societal and individual benefits. Although it concerns innovative knowledge to serve a public good, it also relates to questions of individual integrity and depends heavily on the willingness of people to share information and to accept a central registration. Recently, many discussions have been reported on the usage of big data, which may make people feel vulnerable. In the present study it is argued that both ethical (consent, confidentiality, access, social value) and psychological dimensions (feelings of threat, trust in public institutions, social identification, normative beliefs) are related to these feelings of vulnerability and individual perceptions on big data, and hence may affect the innovative possibilities of big data. We aim to unravel these dimensions by means of qualitative and quantitative research methods among participants of the LifeLines biobank, a large population study in the Netherlands, and a selection of participants who withdraw from participation in LifeLines. This will be in close collaboration with ERCET (European Research Center for Exascale Technology), a program of IBM and University of Groningen. Based on these data generated in face-to-face interviews and written questionnaires, brainstorm sessions will be held with respondents about innovative ways to stimulate sharing and usage of personal data. Together with different companies, these approaches will be tested within LifeLines, to be able to conclude on how society, and more specific health research and innovation, can benefit from the implementation of these innovative approaches.

Aneuploidy, an abnormal chromosomes number, is a hallmark of cancer cells, but, toxic to cells grown in tissue culture. Aneuploidy results from chromosomal instability (CIN), i.e. an increased rate of chromosome missegergation. As cancer cells arise in vivo and not a petridish, this suggests 1) that cancer cells adapt to cope with aneuploidy and/or 2) that cells residing in vivo tolerate aneuploidy better than cultured cells. To test the latter, we will establish an in vivo model to monitor chromosome segregation in developing zebrafish. This will allow, for the first time, to monitor CIN and its consequences in vivo.

Magnetic resonance spectroscopy (NMR or ESR) or magnetic resonance imaging (MRI) are the gold standard for imaging and characterizing samples ranging from complex chemicals to the human body. However, magnetic resonance measurements are not very sensitive and thus substantial amount of sample is needed. Additionally, scanning requires time, which limits dynamic studies. Our team recently has filed a patent for a method that allows to receive the entire spectrum instantaneously and only requires nanoliters of sample. When this method is successfully transferred into an instrument, users of such an instrument like drug discovery companies could benefit from improved time resolution as well as smaller sample volumes. This Demonstrator project aims to develop a prototype of such an instrument, which will be used to attract & convince both instrument developers, drug discovery and characterization companies as end users.