ERC FUNDED PROJECTS

The rupture of an Aortic Aneurysm (AA), which is often lethal, is a mechanical phenomenon that occurs when the wall stress state exceeds the local strength of the tissue. Our current understanding of arterial rupture mechanisms is poor, and the physics taking place at the microscopic scale in these collagenous structures remains an open area of research. Understanding, modelling, and quantifying the micro-mechanisms which drive the mechanical response of such tissue and locally trigger rupture represents the most challenging and promising pathway towards predictive diagnosis and personalized care of AA. The PI's group was recently able to detect, in advance, at the macro-scale, rupture-prone areas in bulging arterial tissues. The next step is to get into the details of the arterial microstructure to elucidate the underlying mechanisms. Through the achievements of AArteMIS, the local mechanical state of the fibrous microstructure of the tissue, especially close to its rupture state, will be quantitatively analyzed from multi-photon confocal microscopy and numerically reconstructed to establish quantitative micro-scale rupture criteria. AArteMIS will also address developing micro-macro models which are based on the collected quantitative data. The entire project will be completed through collaboration with medical doctors and engineers, experts in all required fields for the success of AArteMIS. AArteMIS is expected to open longed-for pathways for research in soft tissue mechanobiology which focuses on cell environment and to enable essential clinical applications for the quantitative assessment of AA rupture risk. It will significantly contribute to understanding fatal vascular events and improving cardiovascular treatments. It will provide a tremendous source of data and inspiration for subsequent applications and research by answering the most fundamental questions on AA rupture behaviour enabling ground-breaking clinical changes to take place.

1 499 783 €

Start date: 2015-04-01, End date: 2020-10-31

Increasing crop yield to feed the world is a grand challenge of the 21st century but it is hampered by diseases caused by filamentous plant pathogens. The arms race between pathogen and plant demands constant adjustment of crop germplasm to tackle emerging pathogen races with new virulence features. To date, most crop disease resistance has relied on specific resistance genes that are effective only against a subset of races. We cannot solely rely on classical resistance genes to keep ahead of the pathogens. There is an urgent need to develop approaches based on knowledge of the pathogen’s Achilles heel: core plant processes that are required for pathogen colonization. Our hypothesis is that disease resistance based on manipulation of host accessibility processes has a higher probability for durability, and is best identified using a broad host-range pathogen. I will employ the filamentous pathogen Phytophthora palmivora to mine plant alleles and unravel host processes providing microbial access in roots and leaves of monocot and dicot plants. In Aim 1 I will utilize plant symbiosis mutants and allelic variation to elucidate general mechanisms of colonization by filamentous microbes. Importantly, allelic variation will be studied in economically relevant barley and wheat to allow immediate translation into breeding programs. In Aim 2 I will perform a comparative study of microbial colonization in monocot and dicot roots and leaves. Transcriptional profiling of pathogen and plant will highlight common and contrasting principles and illustrate the impact of differential plant anatomies. We will challenge our findings by testing beneficial fungi to assess commonalities and differences between mutualist and pathogen colonization. We will use genetics, cell biology and genomics to find suitable resistance alleles highly relevant to crop production and global food security. At the completion of the project, I expect to have a set of genes for resistance breeding.

1 991 054 €

Start date: 2015-09-01, End date: 2022-02-28

Obesity and diabetes have reached pandemic proportions and new therapeutic strategies are critically needed. Brown adipose tissue (BAT), a major source of heat production, possesses significant energy-dissipating capacity and therefore represents a promising target to use in combating these diseases. Recently, I discovered a novel link between circadian rhythm and thermogenic stress in the control of the conserved, calorie-burning functions of BAT. Circadian and thermogenic signaling to BAT incorporates blood-borne hormonal and nutrient cues with direct neuronal input. Yet how these responses coordinately shape BAT energy-expending potential through the regulation of cell surface receptors, metabolic enzymes, and transcriptional effectors is still not understood. My primary goal is to investigate this previously unappreciated network of crosstalk that allows mammals to effectively orchestrate daily rhythms in BAT metabolism, while maintaining their ability to adapt to abrupt changes in energy demand. My group will address this question using gain and loss-of-function in vitro and in vivo studies, newly-generated mouse models, customized physiological phenotyping, and cutting-edge advances in next generation RNA sequencing and mass spectrometry. Preliminary, small-scale validations of our methodologies have already yielded a number of novel candidates that may drive key facets of BAT metabolism. Additionally, we will extend our circadian and thermogenic studies into humans to evaluate the translational potential. Our results will advance the fundamental understanding of how daily oscillations in bioenergetic networks establish a framework for the anticipation of and adaptation to environmental challenges. Importantly, we expect that these mechanistic insights will reveal pharmacological targets through which we can unlock evolutionary constraints and harness the energy-expending potential of BAT for the prevention and treatment of obesity and diabetes.

1 497 008 €

Start date: 2015-05-01, End date: 2020-10-31

With the recognition that wind energy will become an important contributor to the world’s energy portfolio, several wind farms with a capacity of over 1 gigawatt are in planning phase. In the past, engineering of wind farms focused on a bottom-up approach, in which atmospheric wind availability was considered to be fixed by climate and weather. However, farms of gigawatt size slow down the Atmospheric Boundary Layer (ABL) as a whole, reducing the availability of wind at turbine hub height. In Denmark’s large off-shore farms, this leads to underperformance of turbines which can reach levels of 40%–50% compared to the same turbine in a lone-standing case. For large wind farms, the vertical structure and turbulence physics of the flow in the ABL become crucial ingredients in their design and operation. This introduces a new set of scientific challenges related to the design and control of large wind farms. The major ambition of the present research proposal is to employ optimal control techniques to control the interaction between large wind farms and the ABL, and optimize overall farm-power extraction. Individual turbines are used as flow actuators by dynamically pitching their blades using time scales ranging between 10 to 500 seconds. The application of such control efforts on the atmospheric boundary layer has never been attempted before, and introduces flow control on a physical scale which is currently unprecedented. The PI possesses a unique combination of expertise and tools enabling these developments: efficient parallel large-eddy simulations of wind farms, multi-scale turbine modeling, and gradient-based optimization in large optimization-parameter spaces using adjoint formulations. To ensure a maximum impact on the wind-engineering field, the project aims at optimal control, experimental wind-tunnel validation, and at including multi-disciplinary aspects, related to structural mechanics, power quality, and controller design.

1 499 241 €

Start date: 2012-10-01, End date: 2017-09-30