ERC FUNDED PROJECTS

Sex differences in life span and aging are ubiquitous across the animal kingdom and represent a long-standing challenge in evolutionary biology. In most species, including humans, sexes differ not only in how long they live and when they start to senesce, but also in how they react to environmental interventions aimed at prolonging their life span or decelerating the onset of aging. Therefore, sex differences in life span and aging have important implications beyond the questions posed by fundamental science. Both evolutionary reasons and medical implications of sex differences in demographic, reproductive and physiological senescence are and will be crucial targets of present and future research in the biology of aging. Here I propose a two-step approach that can provide a significant breakthrough in our understanding of the biological basis of sex differences in aging. First, I propose to resolve the age-old conundrum regarding the role of sexspecific mortality rate in sex differences in aging by developing a series of targeted experimental evolution studies in a novel model organism – the nematode, Caenorhabditis remanei. Second, I address the role of intra-locus sexual conflict in the evolution of aging by combining novel methodology from nutritional ecology – the Geometric Framework – with artificial selection approach using the cricket Teleogryllus commodus and the fruitfly Drosophila melanogaster. I will directly test the hypothesis that intra-locus sexual conflict mediates aging by restricting the adaptive evolution of diet choice. By combining techniques from evolutionary biology and nutritional ecology, this proposal will raise EU’s profile in integrative research, and contribute to the training of young scientists in this rapidly developing field.

1 391 904 €

Start date: 2010-12-01, End date: 2016-05-31

Today, much interest in several fields of physics is devoted to the study of small, open quantum systems, whose properties are profoundly affected by the environment; i.e., the continuum of decay channels. In nuclear physics, these problems were originally studied in the context of nuclear reactions but their importance has been reestablished with the advent of radioactive-beam physics and the resulting interest in exotic nuclei. In particular, strong theory initiatives in this area of research will be instrumental for the success of the experimental program at the Facility for Antiproton and Ion Research (FAIR) in Germany. In addition, many of the aspects of open quantum systems are also being explored in the rapidly evolving research on ultracold atomic gases, quantum dots, and other nanodevices. A first-principles description of open quantum systems presents a substantial theoretical and computational challenge. However, the current availability of enormous computing power has allowed theorists to make spectacular progress on problems that were previously thought intractable. The importance of computational methods to study quantum many-body systems is stressed in this proposal. Our approach is based on the ab initio no-core shell model (NCSM), which is a well-established theoretical framework aimed originally at an exact description of nuclear structure starting from realistic inter-nucleon forces. A successful completion of this project requires extensions of the NCSM mathematical framework and the development of highly advanced computer codes. The '++' in the project title indicates the interdisciplinary aspects of the present research proposal and the ambition to make a significant impact on connected fields of many-body physics.

1 304 800 €

Start date: 2009-12-01, End date: 2014-11-30

Immune systems are highly variable, but the sources of this variation are poorly understood. Genetic variation only explains a minor fraction of this, and we are unable to accurately predict the risk of immune mediated disease or severe infection in any given individual. I recently found that immune cells and proteins in healthy twins vary because of non-heritable influences (infections, vaccines, microbiota etc.), with only minor influences from heritable factors (Brodin, et al, Cell 2015). When and how such environmental influences shape our immune system is now important to understand. Birth represents the most transformational change in environment during the life of any individual. I propose, that environmental influences at birth, and during the first months of life could be particularly influential by imprinting on the regulatory mechanisms forming in the developing immune system. Adaptive changes in immune cell frequencies and functional states induced by early-life exposures could determine both the immune competence of the newborn, but potentially also its long-term trajectory towards immunological health or disease. Here, I propose a study of 1000 newborn children, followed longitudinally during their first 1000 days of life. By monitoring immune profiles and recording many environmental influences, we hope to understand how early life exposures can influence human immune system development. We have established a new assay based on Mass Cytometry and necessary data analysis tools (Brodin, et al, PNAS 2014), to simultaneously monitor the frequencies, phenotypes and functional states of more than 200 blood immune cell populations from only 100 microliters of blood. By monitoring environmental influences at regular follow-up visits, by questionnaires, serum measurements of infection, and gut microbiome sequencing, we aim to provide the most comprehensive analysis to date of immune system development in newborn children.

1 422 339 €

Start date: 2016-07-01, End date: 2021-06-30

The core function of all brains is to compute the current state of the world, compare it to the desired state of the world and select motor programs that drive behavior minimizing any mismatch. The circuits underlying these functions are the key to understand brains in general, but so far they are completely unknown. Three problems have hindered progress: 1) The animal’s desired state of the world is rarely known. 2) Most studies in simple models have focused on sensory driven, reflex-like processes, and not considered self-initiated behavior. 3) The circuits underlying complex behaviors in vertebrates are widely distributed, containing millions of neurons. With this proposal I aim at overcoming these problems using insects, whose tiny brains solve the same basic problems as our brains but with 100,000 times fewer cells. Moreover, the central complex, a single conserved brain region consisting of only a few thousand neurons, is crucial for sensory integration, motor control and state-dependent modulation, essentially being a ‘brain in the brain’. To simplify the problem further I will focus on navigation behavior. Here, the desired and actual states of the world are equal to the desired and current headings of the animal, with mismatches resulting in compensatory steering. I have previously shown how the central complex encodes the animal’s current heading. Now I will use behavioral training to generate animals with highly defined desired headings, and correlate neural activity with the animal’s ‘intentions’ and actions - at the level of identified neurons. To establish the involved conserved core circuitry valid across insects I will compare species with distinct lifestyles. Secondly, I will reveal how these circuits have evolved to account for each species’ unique ecology. The proposed work will provide a coherent framework to study key concepts of fundamental brain functions in unprecedented detail - using a single, conserved, but flexible neural circuit.

1 500 000 €

Start date: 2017-01-01, End date: 2022-08-31