ERC FUNDED PROJECTS

Why is the world green? Because predators control herbivores, allowing plants to flourish. This >50 years old answer to the deceptively simple question remains controversial. After all, plants are also protected from herbivores physically and by secondary chemistry. My goal is to test novel aspects of the “green world hypothesis”: ● How the importance of top-down effects varies with forest diversity and productivity along a latitudinal gradient? ● How the key predators, birds, bats and ants, contribute to top-down effects individually and in synergy? I strive to understand this because: ● While there is evidence that predators reduce herbivore abundance and enhance plant growth, the importance of top-down control is poorly understood across a range of forests. ● The importance of key predatory groups, and their antagonistic and synergic interactions, have been rarely studied, despite their potential impact on ecosystem dynamics in changing world. I wish to achieve my goals by: ● Factorial manipulations of key insectivorous predators (birds, bats, ants) to measure their effects on lower trophic levels in forest understories and canopies, accessed by canopy cranes, along latitudinal gradient spanning 75o from Australia to Japan. ● Studying compensatory effects among predatory taxa on herbivore and plant performance. Why this has not been done before: ● Factorial experimental exclusion of predatory groups replicated on a large spatial scale is logistically difficult. ● Canopy crane network along a latitudinal gradient has only recently become available. I am in excellent position to succeed as I have experience with ● foodweb experiments along an elevation gradient in New Guinea rainforests, ● study of bird, bat and arthropod communities. If the project is successful, it will: ● Allow understanding the importance of predators from temperate to tropical forests. ● Establish a network of experimental sites along a network of canopy cranes open for follow-up research.

1 455 032 €

Start date: 2018-12-01, End date: 2023-11-30

The goal of the proposed research is to examine how the independent and combined effects of childhood adiposity (assessed by body mass index [BMI]; kg/m2) height, change in BMI and height, and pubertal timing from the ages of 7 to 13 years are associated with the risk of cancer incidence in adulthood. Greater body size (adipose tissue and different types of lean tissue) reflecting past or ongoing growth may increase the risk of cancer in individuals as greater numbers of proliferating cells increase the risk that mutations leading to the subsequent development of cancer occur. As childhood is a period of growth, it is plausible that it is of particular relevance for the early establishment of the risk of cancer. Data from the Copenhagen School Health Records Register, which is based on a population of schoolchildren born between 1930-1983 and contains computerised weight and height measurements on >350.000 boys and girls in the capital city of Denmark, as well as data from other cohorts will be used. Survival analysis techniques and the newly developed Dynamic Path Analysis model will be used to examine how body size (BMI and height) at each age from 7 to 13 years as well as change in body size during this period is associated with the risk of multiple forms of cancer in adulthood with a simultaneous exploration of the effects of birth weight and pubertal timing. Additionally, potential effects of childhood and adult health and social circumstances will be investigated in sub-cohorts with this information available. Results from this research will demonstrate if childhood is a critical period for the establishment of the risk for cancer in adulthood and will lead into mechanistic explorations of the associations at the biological level, investigations into associations between childhood body size and mortality and contribute to developing improved definitions of childhood overweight and obesity that are based upon long-term health outcomes.

1 199 998 €

Start date: 2012-02-01, End date: 2017-01-31

Background: Acrylamide is a chemical formed in many commonly consumed foods and beverages. It is neurotoxic, crosses the placenta and has been associated with restriction of fetal growth in humans. In animals, acrylamide causes heritable mutations, tumors, developmental toxicity, reduced fertility and impaired growth. Therefore, the discovery of acrylamide in food in 2002 raised concern about human health effects worldwide. Still, epidemiological studies are limited and effects on health of prenatal exposure have never been evaluated. Research gaps: Epidemiological studies have mostly addressed exposure during adulthood, focused on cancer risk in adults, and relied on questionnaires entailing a high degree of exposure misclassification. Biomarker studies on prenatal exposure to acrylamide from diet are critically needed to improve exposure assessment and to determine whether acrylamide leads to major diseases later in life. Own results: I have first authored a prospective European study showing that prenatal exposure to acrylamide, estimated by measuring hemoglobin adducts in cord blood, was associated with fetal growth restriction, for the first time. Objectives: To determine the effects of prenatal exposure to acrylamide alone and in combination with other potentially toxic adduct-forming exposures on the health of children and young adults. Methods: Both well-established and innovative biomarker methods will be used for characterization of prenatal exposure to acrylamide and related toxicants in blood from pregnant women and their offspring in prospective cohort studies with long-term follow-up. Risk of neurological disorders, impaired cognition, disturbed reproductive function and metabolic outcomes such as obesity and diabetes will be evaluated. Perspectives: CHIPS project will provide a better understanding of the impact of prenatal exposure to acrylamide from diet on human health urgently needed for targeted strategies for the protection of the health.

1 499 531 €

Start date: 2018-07-01, End date: 2023-06-30

G protein-coupled receptors make up both the largest membrane protein and drug target families. DE-ORPHAN aims to determine the close functional context; specifically physiological agonists and signaling pathways; and provide the first research tool compounds, of orphan peptide receptors. Determination of physiological agonists (aka de-orphanization), by high-throughput screening has largely failed. We will introduce a new research strategy: 1) developing highly innovative bioinformatics methods for handpicking of all orphan receptor targets and candidate ligand screening libraries; and 2) employing a screening technique that can measure all signaling pathways simultaneously. The first potent and selective pharmacological tool compounds will be identified by chemoinformatic design of focused screening libraries. We will establish the ligands’ structure-activity relationships important for biological activity and further optimization towards drugs. The first potent and selective Gs- and G12/13 protein inhibitors will be designed by structure-based re-optimization from a recent crystal structure of a Gq-inhibitor complex, and applied to determine orphan receptor signaling pathways and ligand pathway-bias. They will open up for efficient dissection of important signaling networks and development of drugs with fewer side effects. DE-ORPHANs design hypotheses are based on unique computational methods to analyze protein and ligand similarities and are founded on genomic and protein sequences, structural data and ligands. The interdisciplinary research strategy applies multiple ligands acting independently but in concert to provide complementary receptor characterization. The results will allow the research field to advance into studies of receptor functions and exploitation of druggable targets, ligands and mechanisms. Which physiological insights and therapeutic breakthroughs will we witness when these receptors find their place in human pharmacology and medicine?

1 499 926 €

Start date: 2015-05-01, End date: 2020-04-30

Comparative studies of inbreeding and evolution in non-model animal populations: a research proposal directed towards integrating ecological and evolutionary research on inbreeding. Specifically, my aim is to apply novel ecogenomics tools in the study of evolutionary consequences of inbreeding in non-model animal populations. At present, our understanding of inbreeding is dominated by studies of a small number of model organisms. I will undertake comparative studies on inbreeding effects in a genus of spiders containing independently evolved naturally inbreeding species as well as outcrossing sister species. The study of a naturally inbreeding animal species will provide unique insights to consequences of inbreeding for population genetic structure, genome-wide genetic diversity, and evolution of life history traits. Social spiders are not only unique because they naturally inbreed, but also by being cooperative and showing allomaternal brood care including self-sacrifice, and they evolve highly female-biased sex-ratios, a trait that is not well understood in diploid species. My research objectives are 1) to establish a robust phylogeny for comparative studies; 2) to quantify the effects of inbreeding on the genetic diversity within and between populations; 3) to estimate gene flow among inbred lineages to determine whether inbred lineages diversify but retain the potential for gene exchange, or undergo cryptic speciation; 4) to determine effects of inbreeding on gene expression; 5) to investigate the mechanism underlying the genetic sex determination system that cause female biased sex-ratios; and finally 6) to determine whether sex-ratio is under adaptive parental control in response to genetic relatedness and ecological constraints. Addressing these objectives will generate novel insights and expand current knowledge on the evolutionary ecology of inbreeding in wild animal populations.

1 497 248 €

Start date: 2012-01-01, End date: 2017-09-30

Chlamydiae are a unique group of obligate intracellular bacteria that comprises symbionts of protozoa as well as important pathogens of humans and a wide range of animals. The intracellular life style and the obligate association with a eukaryotic host was established early in chlamydial evolution and possibly also contributed to the origin of the primary phototrophic eukaryote. While much has been learned during the past decade with respect to chlamydial diversity, their evolutionary history, pathogenesis and mechanisms for host cell interaction, very little is known about genome dynamics, genome evolution, and adaptation in this important group of microorganisms. This project aims to fill this gap by three complementary work packages using experimental evolution approaches and state-of-the-art genome sequencing techniques. Chlamydiae that naturally infect free-living amoebae, namely Protochlamydia amoebophila and Simkania negevensis, will be established as model systems for studying genome evolution of obligate intracellular bacteria (living in protozoa). Due to their larger, less reduced genomes compared to chlamydial pathogens, amoeba-associated Chlamydiae are ideally suited for these investigations. Experimental evolution approaches – among the prokaryotes so far almost exclusively used for studying free-living bacteria – will be applied to understand the genomic and molecular basis of the intracellular life style of Chlamydiae with respect to host adaptation, host interaction, and the character of the symbioses (mutualism versus parasitism). In addition, the role of amoebae for horizontal gene transfer among intracellular bacteria will be investigated experimentally. Taken together, this project will break new ground with respect to evolution experiments with intracellular bacteria, and it will provide unprecedented insights into the evolution and adaptive processes of intracellular bacteria in general, and the Chlamydiae in particular.

1 499 621 €

Start date: 2012-01-01, End date: 2016-12-31

The widespread recognition that interactions with microbes drive animal health, development and evolution is transforming biology, but we so far understand the underlying mechanisms in very few systems. Considering that virtually every animal on Earth evolved with and among the microbes in its environment, there is still immense potential for discovering fundamentally new mechanisms of interaction among the staggering diversity of animals and their microbial symbionts in nature. The ancient and exclusive association between marine lucinid clams and chemosynthetic symbiotic bacteria is ideal for investigating these interactions. Lucinidae is one of the most widespread and species-rich animal families in the oceans today, and has lived in symbiosis for more than 400 million years. The clam’s outstanding ability to select one specific symbiont from the trillions of bacteria in its environment challenges widely held assumptions about the function and specificity of the innate immune system. Symbiont-free juveniles can be raised in the lab, and experimentally infected, allowing unmatched insights into the early development of this symbiosis. Although the symbiont infection is specific to gill cells, symbiont-encoded proteins can be found in distant parts of the animal that are symbiont-free. I will combine cutting-edge molecular tools and experimental infection to better understand three key aspects of host-microbe interactions in these clams: 1) Acquisition and selection of microbes during animal development, 2) Maintenance along animal lifetimes through molecular communication and exchange, and 3) Emergence and perpetuation over evolution. I hypothesize that intracellular bacterial symbionts fundamentally alter host biology, and these effects are not limited to the location where symbionts are housed, but can affect distant organ systems. My overarching goal is to understand the molecular basis for these effects, and their evolutionary history.

1 499 561 €

Start date: 2019-02-01, End date: 2024-01-31

"Earth’s environment is ongoing massive changes with strong impacts on ecosystems and their services to human societies. It is thus crucial to improve understanding of ecosystem functioning and its dynamics under environmental change. I propose to do this by assessing the novel hypothesis that ecosystem functioning is subject to long-term constraints mediated by biodiversity effects and driven by past climate change and other historical factors. If supported, we will have to rethink ecosystem ecology, as traditionally ecosystem functioning is understood as the outcome of contemporary environmental drivers and their interplay with dominant species. I will employ an unconventional macroecological approach to ecosystem ecology to investigate this hypothesis for major organism groups and ecosystems across continents, modeling effects of historical factors such as past climate change. My specific objectives are to assess if and how (1) large-scale patterns in functional diversity of a key producer group, vascular plants, and (2) a key consumer group, mammals, are affected by historical factors; (3) if and how plant and mammal functional diversity are linked, and, if such links exist, how and to what extent they are shaped by historical factors; (4) if and how large-scale patterns in vegetation-related ecosystem functioning are shaped by historical factors; (5) if ecosystem functioning is linked to diversity of plants and mammals, and if such links exist, if they are shaped by historical factors; and finally (6) directly translate my findings into a novel framework for predicting spatiotemporal dynamics of ecosystem functioning that accounts for historical constraints. The project relies on extensive geospatial data now available on ecosystem functioning, species distributions, and functional traits as well as on paleodistributions, phylogenies, paleoclimate, environment, and human impacts, in combination with advanced statistical and mechanistic modeling."

1 499 930 €

Start date: 2013-01-01, End date: 2017-12-31

The goal of this proposal is to support the paradigm shift in the health care of people with multiple chronic conditions in Europe from a focus on disease-based curative models to holistic person-centered self-care through personalized,supervised exercise therapy and education. The problem:The impact of multimorbidity on the individual and society is massive and much greater than the impact of single chronic conditions alone. However, effective treatments are missing and research and health care reinforce an inefficient and burdensome single-disease framework. The solution:Exercise has the potential to disrupt the ‘vicious cycle’ of systemic inflammation associated with chronic conditions and improve health in multimorbidity. A personalized exercise and education program aimed at supporting subsequent self-management by the individual will be developed in an interdisciplinary collaboration, building on evidence from biomarkers, patient involvement and methodological expertise. Self-reported,physiological and societal effects will be investigated in a randomized controlled trial comparing the personalized program with standard single-disease models of care. Scientific and public dissemination and implementation ensuring significant personal and societal benefit is fundamental to the proposal. The proposal is associated with high risk, as the current disease-based curative models involve treatment by several highly specialized health care providers, while the new person-centered self-management model is centered on a personalized program delivered by one health care provider. The ground-breaking nature of this proposal lies in its potential to revolutionize how health care is organized for people with multimorbidity, by giving them one primary care provider, and how we use non-surgical treatment in health care and science by bringing the concept of precision medicine into multimorbidity and utilizing it to improve treatment outcome with exercise therapy as the model.

1 499 230 €

Start date: 2019-08-01, End date: 2024-07-31