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.

A major challenge in ecology is the need for a better theoretical framework for understanding how species assemblages (ecological communities) arise, why some are species-rich and others species-poor, and why some species are present or dominant whereas others are not. Current community assembly theory is largely based on static models. However, ecological dynamics (e.g. ecological drift, competition, immigration), or evolutionary dynamics (e.g. genetic drift, natural selection, speciation) generate continual changes in the constituents of communities and the sources from which they are assembled. The dynamical models that do exist do not take the community perspective or do not readily allow inferences from data. Moreover, there is often a mismatch between models and data. I propose to solve these problems simultaneously by developing a fully stochastic, dynamical and data-friendly theory of community assembly, and testing and informing this theory with model-oriented experiments and field studies of both macro-organisms and micro-organisms. The theory will contain models of speciation, extinction, immigration and demographic change that vary in spatial, phylogenetic and biotic complexity, and which I will design for confrontation with data by providing each model?s likelihood given the data. I will conduct evolutionary experiments on the mite Tetranychus urticae and the bacterium Escherichia coli, which are ideal model organisms due to their short generation times. The experiments will provide insight into how diversity affects diversification, a great unknown in current macro-evolutionary theory. Apart from these highly controlled experiments, I will apply the theory to naturally occurring microlandsnails in South-East Asia, and micro-organisms in geothermal pools in New Zealand. Their small size, endemism and spatially limited, discrete habitat create a miniature world that facilitates sampling and confrontation with models. The proposed research will provide software tools for scientists and conservationists to assess the processes underlying natural communities and predict their future composition and diversity.

Arctic and subarctic ecosystems cover 22% of Earths terrestrial surface. Global warming is expected to have a major impact on the arctic flora, as temperature zones move northwards. The factors affecting the colonization of new areas, however, are not well understood. Oxyria digyna is a pioneer plant species in arctic and alpine glacial forelands. Our preliminary data show that O. digyna harbors endophytic bacterial communities with ecologically significant traits and that these bacteria also colonize seeds. We here propose to conduct a comprehensive study on the diversity and function of O. digyna endobacterial communities. Endophytic bacteria often form mutualistic relationships with their hosts. Awareness of the potential benefits of endophytes has grown rapidly in recent years. Most research on endophytic bacteria concerns plants in temperate climate zones, whereas the diversity and role of endophytic bacteria in arctic ecosystems is virtually unknown. The main research hypotheses are that (1) endophytic bacterial communities are dynamic and integral parts of O. digyna in all life stages, (2) part of these communities is carried in seeds, and these bacteria play key roles in seedling establishment, (3) O. digyna selects complementing endobacterial companions from the rhizosphere, making it a competent colonizer of the highly demanding arctic and alpine habitats. The approach will combine taxonomic and trait-based community analyses and bioassays. This enables the detection and identification of bacterial communities and traits in different plant tissues, seasons and developmental stages, and linking endobacterial community traits to plant functions.

In polar regions, major climate-gas exchange events occur during the period of sea-ice melt and associated growth of phytoplankton. Important compounds are dimethylsulfide (DMS), a potentially climate-cooling gas, and bromocarbons, precursors of the reactive compound bromine oxide. On a global scale, DMS is thought to counterbalance greenhouse gases, such as CO2. However, recent studies have shown that bromine chemistry not only leads to loss of ozone, but also to loss of DMS, thereby reducing the latter?s cooling effect. Such interactions have important implications for climate models, but ground-truth data to validate such models are lacking. This project aims to fill that gap, by doing time-series measurements of DMS and associated compounds at the Rothera Time Series (RaTS) site. We will collaborate with UEA/BAS bromocarbon research, which started at RaTS in 2005. High fluxes of DMS are episodic and have been found associated with the melting of sea ice. With major changes in sea-ice coverage taking place at the west side of the Antarctic Peninsula, Rothera is extremely well situated to study the effect of retreating sea ice on climate-gas production. We propose to measure both the water and ice phase for its DMS and related-compounds content. The methods to be used will be based on recently developed methods using stable-isotope additions and mass spectrometry. Data will be related to the community structure and physicochemical characteristics of the area. This work will provide the first polar DMS time series ever and will form an important input for new polar coupled-climate models.