ERC FUNDED PROJECTS

Magnetic fields in stars, planets, accretion discs, and galaxies are believed to be the result of a dynamo process converting kinetic energy into magnetic energy. This work focuses on the solar dynamo, but dynamos in other astrophysical systems will also be addressed. In particular, direct high-resolution three-dimensional simulations are used to understand particular aspects of the solar dynamo and ultimately to simulate the solar dynamo as a whole. Phenomenological approaches will be avoided in favor of obtaining rigorous results. A major problem is catastrophic quenching, i.e. the decline of dynamo effects in inverse proportion to the magnetic Reynolds number, which is huge. Tremendous advances have been made in the last few years since the cause of catastrophic quenching in dynamos has been understood in terms of magnetic helicity evolution. The numerical tools are now in place to allow for magnetic helicity fluxes via coronal mass ejections, thus alleviating catastrophic quenching. This work employs simulations in spherical shells, augmented by Cartesian simulations in special cases. The roles of the near-surface shear layer, the tachocline, as well as pumping in the bulk of the convection zone are to be clarified. The Pencil Code will be used for most applications. The code is third order in time and sixth order in space and is used for solving the hydromagnetic equations. It is a public domain code developed by roughly 20 scientists world wide and maintained under an a central versioning system at Nordita. Automatic nightly tests of currently 30 applications ensure the integrity of the code. It is used for a wide range of applications and may include the effects of radiation, self-gravity, dust, chemistry, variable ionization, cosmic rays, in addition to those of magnetohydrodynamics. The code with its infrastructure offers a good opportunity for individuals within a broad group of people to develop new tools that may automatically be useful to others.

2 220 000 €

Start date: 2009-02-01, End date: 2014-01-31

BEACON aims at performing an ambitious multi-disciplinary (optical, radio astronomy and theoretical physics) study to enable a fundamentally improved understanding of gravitation and space-time. For almost a century Einstein's general relativity has been the last word on gravity. However, superstring theory predicts new gravitational phenomena beyond relativity. In this proposal I will attempt to detect these new phenomena, with a sensitivity 20 times better than state-of-the-art attempts. A successful detection would take physics beyond its current understanding of the Universe. These new gravitational phenomena are emission of dipolar gravitational waves and the violation of the strong equivalence principle (SEP). I plan to look for them by timing newly discovered binary pulsars. I will improve upon the best current limits on dipolar gravitational wave emission by a factor of 20 within the time of this proposal. I also plan to develop a test of the Strong Equivalence Principle using a new pulsar/main-sequence star binary. The precision of this test is likely to surpass the current best limits within the time frame of this proposal and then keep improving indefinitely with time. This happens because this is the cleanest gravitational experiment ever carried out. In order to further these goals, I plan to build the ultimate pulsar observing system. By taking advantage of recent technological advances in microwave engineering (particularly sensitive ultra-wide band receivers) digital electronics (fast analogue-to-digital converters and digital spectrometers) and computing, my team and me will be able to greatly improve the sensitivity and precision for pulsar timing experiments and exploit the capabilities of modern radio telescopes to their limits. Pulsars are the beacons that will guide me in these new, uncharted seas.

1 892 376 €

Start date: 2011-09-01, End date: 2016-08-31

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are common in elderly and the prevalence of these is increasing. AD and PD have distinct pathogenesis, which precede the overt clinical symptoms by 10-15 years, opening a window for early diagnosis and treatment. New disease-modifying therapies are likely to be most efficient if initiated before the patients exhibit overt symptoms, making biomarkers for early diagnosis crucial for future clinical trials. Validated biomarkers would speed up initiation of treatment, avoid unnecessary investigations, and reduce patient insecurity. AIMS: (1) identify and validate accurate and cost-effective blood-based biomarkers for early identification of those at high risk to develop AD and PD, (2) develop algorithms using advanced imaging and cerebrospinal fluid biomarkers for earlier more accurate diagnoses, and (3) better understand the underlying pathology and early progression of AD and PD, aiming at finding new relevant drug targets. We will assess well-characterized and clinically relevant populations of patients and healthy elderly. We will use population- and clinic-based cohorts and follow them prospectively for 4 year. Participants will undergo neurocognitive evaluation, provide blood and cerebrospinal fluid, and have brain imaging using advanced MRI protocols and a newly developed PET-tracer visualizing brain amyloid. Sample will be analyzed with quantitative mass spectrometry and high sensitivity immunoassays. New biomarkers and brain imaging techniques will aid early diagnosis and facilitate the development of disease-modifying therapies, since treatment can start earlier in the disease process. New methods to quantify relevant drug targets, such as oligomers of β-amyloid and α-synuclein, will be vital when selecting drug candidates for large-scale clinical trials. By improving both diagnosis and therapies the social and economic burden of dementia might be reduced by expanding the period of healthy and active aging

1 500 000 €

Start date: 2013-06-01, End date: 2018-05-31

Xenon biosensors have an outstanding potential to increase the significance of magnetic resonance imaging (MRI) in molecular imaging and to combine the advantages of MRI with the high sensitivity of hyperpolarized Xe-129 and the specificity of a functionalized contrast agent. Based on new detection schemes (Hyper-CEST method) in Xe MRI, this novel concept in molecular diagnostics will be made available for biomedical applications. The advancement focuses on high-sensitivity in vitro diagnostics for localization of tumour cells in cell cultures and first demonstrations on animal models based on a transferrin-functionalized biosensor. Such a sensor will enable detection of subcutaneous tumours at high sensitivity without any background signal. More detailed work on the different available Hyper-CEST contrast parameters focuses on an absolute quantification of new molecular markers that will improve non-invasive tumour diagnostics significantly. NMR detection of functionalized Xe biosensors have the potential to close the sensitivity gap between modalities of nuclear medicine like PET/SPECT and MRI without using ionizing radiation or making compromises in penetration depth like in optical methods.

1 848 600 €

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

The human hematopoietic system is a paradigmatic, stem cell-maintained organ with enormous cell turnover. Hundreds of billions of new blood cells are produced each day. The process is tightly regulated, and susceptible to perturbation due to genetic variation. In this project, we will explore an innovative, population-genetic approach to find regulators of blood cell formation. Unlike traditional studies on hematopoiesis in vitro or in animal models, we will exploit natural genetic variation to identify DNA sequence variants and genes that influence blood cell formation in vivo in humans. Instead of inserting artificial mutations in mice, we will read out ripples from the experiments that nature has performed during evolution. Building on our previous work, unique population-based materials, mathematical modeling, and the latest genomics and genome editing techniques, we will: 1. Develop high-resolution association data and analysis methods to find DNA sequence variants influencing human hematopoiesis, including stem- and progenitor stages. 2. Identify sequence variants and genes influencing specific stages of adult and fetal/perinatal hematopoiesis. 3. Define the function, and disease associations, of identified variants and genes. Led by the applicant, the project will involve researchers at Lund University, Royal Institute of Technology and deCODE Genetics, and will be carried out in strong environments. It has been preceded by significant preparatory work. It will provide a first detailed analysis of how genetic variation influences human hematopoiesis, potentially increasing our understanding, and abilities to control, diseases marked by abnormal blood cell formation (e.g., leukemia).

2 000 000 €

Start date: 2018-10-01, End date: 2023-09-30

There is a large need for revitalization of the research on coronary heart disease (CHD) including: a) improved risk prediction and more adequate individually-tailored treatment; and b) new targets for drug development based on pathways previously unknown to be involved in CHD pathophysiology. The overall goal of this proposal is to improve prevention and treatment of CHD through better understanding of the biology underlying disease development, identification of new biomarkers for improved risk prediction, and discovery of novel targets for drug development. The specific aims are to: 1) Establish and characterize causal genes in known CHD loci (gene regions) through: a) resequencing of known CHD loci; b) expression profiling in liver, arteries, myocardium and skeletal muscle; c) high-throughput protein profiling; and d) experimental follow-up in zebrafish (Danio rerio) models. 2) Discover new proteins, metabolites and pathways involved in CHD pathophysiology using global proteomic and metabolomic profiling to provide new biomarkers and drug targets. We will integrate genomic, transcriptomic, metabolomic and proteomic data from five longitudinal, population-based cohort studies with detailed phenotyping and one study with tissue collections for expression studies. The cohort studies include 36,907 individuals; there are 3,093 prevalent CHD cases at baseline and the estimated number of incident (new) events in previously healthy by 2016 is 2,202. In addition, we work with zebrafish model systems to establish causal CHD genes and characterize their mechanisms of action. We have access to unique study materials, state-of-the art methods, and a strong track record of successful projects in this field. To our knowledge, there are no other groups combining -omics methods to elucidate the whole chain from DNA variation to overt CHD in such large and well-characterized study samples. Further, we are unaware of other groups using zebrafish models to screen for and characterize causal CHD genes. Our work is anticipated to lead to new important insights into the pathophysiology of CHD, identification of new biomarkers for improved risk prediction, and discovery of novel targets for drug development.

1 498 224 €

Start date: 2014-01-01, End date: 2018-12-31

The proposed project will significantly improve the insight in the processes that have changed a comet nucleus or asteroid since their formation. These processes typically go along with activity, the observable release of gas and/or dust. Understanding the evolutionary processes of comets and asteroids will allow us to answer the crucial question which aspects of these present-day bodies still provide essential clues to their formation in the protoplanetary disc of the early solar system. Ground-breaking progress in understanding these fundamental questions can now be made thanks to the huge and unprecedented data set returned between 2014 and 2016 by the European Space Agency’s Rosetta mission to comet 67P/Churyumov-Gerasimenko, and by recent major advances in the observational study of active asteroids facilitated by the increased availability of sky surveys and follow-on observations with world-class telescopes. The key aims of this proposal are to - Obtain a unified quantitative picture of the different erosion processes active in comets and asteroids, - Investigate how ice is stored in comets and asteroids, - Characterize the ejected dust (size distribution, optical and thermal properties) and relate it to dust around other stars, - Understand in which respects comet 67P can be considered as representative of a wider sample of comets or even asteroids. We will follow a highly multi-disciplinary approach analyzing data from many Rosetta instruments, ground- and space-based telescopes, and connect these through numerical models of the dust dynamics and thermal properties.

1 484 688 €

Start date: 2018-03-01, End date: 2023-02-28

We propose to carry out a project which will produce a decisive step towards improving the accuracy of the Hubble constant as determined from the Cepheid-SN Ia method to 1%, by using 28 extremely rare eclipsing binary systems in the LMC which offer the potential to determine their distances to 1%. To achieve this accuracy we will reduce the main error in the binary method by interferometric angular diameter measurements of a sample of red clump stars which resemble the stars in our binary systems. We will check on our calibration with similar binary systems close enough to determine their orbits from interferometry. We already showed the feasibility of our method which yielded the best-ever distance determination to the LMC of 2.2% from 8 such binary systems. With 28 systems and the improved angular diameter calibration we will push the LMC distance uncertainty down to 1% which will allow to set the zero point of the Cepheid PL relation with the same accuracy using the large available LMC Cepheid sample. We will determine the metallicity effect on Cepheid luminosities by a) determining a 2% distance to the more metal-poor SMC with our binary method, and by b) measuring the distances to LMC and SMC with an improved Baade-Wesselink (BW) method. We will achieve this improvement by analyzing 9 unique Cepheids in eclipsing binaries in the LMC our group has discovered which allow factor- of-ten improvements in the determination of all basic physical parameters of Cepheids. These studies will also increase our confidence in the Cepheid-based H0 determination. Our project bears strong synergy to the Gaia mission by providing the best checks on possible systematic uncertainties on Gaia parallaxes with 200 binary systems whose distances we will measure to 1-2%. We will provide two unique tools for 1-3 % distance determinations to individual objects in a volume of 1 Mpc, being competitive to Gaia already at a distance of 1 kpc from the Sun.

2 360 500 €

Start date: 2016-11-01, End date: 2021-10-31

Key challenges in endoscopic tumor diagnosis and therapy consist of the detection and discrimination of malignant tissue as well as the precise navigation of medical instruments. Currently, a low level of sensitivity and specificity in tumor detection and lack of global orientation lead to both over- and undertreatment, tumor recurrence, intra-operative complications, and high costs. The goal of this multidisciplinary project is to revolutionize clinical endoscopic imaging based on the systematic integration of two new but independant fields of research up until this point: Biophotonics and computer-assisted interventions (COMputational BIOphotonics in endoSCOPY). For the first time, quantitative multi-modal imaging biomarkers based on structural and functional data are being developed to enhance the physician’s view by providing information that cannot be seen with the naked eye. To this extent, white light images co-registered with multispectral optical and photoacoustic images will be processed in a combined manner to dynamically reconstruct not only the visible surface in 3D but also subsurface anatomical and functional detail such as 3D vessel topology, blood volume and oxygenation. Spatio-temporal registration of multi-modal data acquired before and during the procedure will enable (1) the highly specific local tissue classification and discrimination based on tissue shape, texture, function and radiological contrast imagery as well as (2) global context-aware instrument guidance. This innovative approach to radiation-free real-time imaging will be implemented and evaluated by means of computer-assisted colonoscopy and laparoscopy. The potential socioeconomic impact of providing high precision minimally-invasive tumor diagnosis and therapy at low cost is extremely high.

1 499 699 €

Start date: 2015-07-01, End date: 2020-06-30

Studying quasars (actively accreting supermassive black holes) and galaxies at the earliest cosmic epochs is one of the prime objectives in modern astrophysics. How the first luminous sources formed and reionized the universe is one of the most fundamental open questions in cosmology. Likewise, a detailed characterization of the evolution of the cosmic molecular gas density, which lies at the heart of galaxy evolution, is a fundamental goal in observational astrophysics. The proposed program capitalizes on current and upcoming facilities and encompasses three aspects: The first (I) will use the recently started Pan-STARRS1 survey to identify a sizeable sample of z>7 quasars, i.e. when the universe was less than 0.8 Gyr old (<1/15th of today’s age), to statistically probe black hole growth in the Epoch of Reionization. The second project (II) will characterize the physical properties of z~6 and z~7 quasar hosts selected from project (I) and the SDSS / VISTA VIKING surveys using new observational NIR/(sub)millimeter capabilities, including ALMA (observations approved in cycle 0). The last project (III) will use the IRAM Plateau de Bure Interferometer, and ALMA, to embark on the first molecular deep field which will provide a complete ‘blind’ census of the molecular gas density through cosmic times (from z~1 to z~8, approved pilot program). The overarching goal of this ERC proposal is thus to greatly increase our understanding of the physical properties of the earliest massive objects in the universe, and to shed first light on the evolution of the cosmic molecular gas density in galaxies after the universe emerged from the cosmic ‘dark ages’. The PI is internationally recognized as a leader in molecular gas studies of high-redshift galaxies, and through his track record and access to the needed combination of research facilities, is uniquely positioned to successfully lead this program.

1 439 000 €

Start date: 2012-11-01, End date: 2017-10-31

"Understanding the physics of galaxy formation is arguably among the greatest problems in modern astrophysics. Recent cosmological simulations have demonstrated that ""feedback"" by star formation, supernovae and active galactic nuclei appears to be critical in obtaining realistic disk galaxies, to slow down star formation to the small observed rates, to move gas and metals out of galaxies into the intergalactic medium, and to balance radiative cooling of the low-entropy gas at the centers of galaxy clusters. This progress still has the caveat that ""feedback"" was modeled empirically and involved tuning to observed global relations, substantially weakening the predictive power of hydrodynamic simulations. More problematic, these simulations neglected cosmic rays and magnetic fields, which provide a comparable pressure support in comparison to turbulence in our Galaxy, and are known to couple dynamically and thermally to the gas. Building on our previous successes in investigating these high-energy processes, we propose a comprehensive research program for studying the impact of cosmic rays on the formation of galaxies and clusters. To this end, we will study cosmic-ray propagation in magneto-hydrodynamic turbulence and improve the modeling of the plasma physics. This will enable us to perform the first consistent magneto-hydrodynamical and cosmic-ray simulations in a cosmological framework, something that has just now become technically feasible. Through the use of an advanced numerical technique that employs a moving mesh for calculating hydrodynamics, we will achieve an unprecedented combination of accuracy, resolution and physical completeness. We complement our theoretical efforts with a focused observational program on the non-thermal emission of galaxies and clusters, taking advantage of new capabilities at radio to gamma-ray wavelengths and neutrinos. This promises important and potentially transformative changes of our understanding of galaxy formation."

2 000 000 €

Start date: 2016-04-01, End date: 2021-03-31

My recent discoveries show that mosaic loss of chromosome Y (LOY) in peripheral blood is associated with increased risks of cancer and Alzheimer’s disease (AD). These conditions are responsible for >50% of morbidity/mortality in aging men. More than 15% of men older than 70 show some degree of LOY and these men survive on average only half as long as men without LOY. Smoking is strongly associated with LOY and remarkably, the fraction of cells with LOY decreases after cessation of smoking. Cells with LOY can be detected, and disease risks predicted, many years before clinical manifestation of disease. These results of associations between LOY, cancer and smoking have been published in Nature Genetics and Science during 2014. The overall objective of the proposal is to develop LOY as a new, strong and predictive biomarker. To this end, the research program focuses on three objectives: 1) expanding the study of LOY and associations with disease risks in still larger cohorts; 2) investigating functional aspects of LOY; and 3) develop improved technology for LOY-detection. The successful execution of the project is essential before LOY-testing in clinics can be realized. Diagnosis of cancer and AD in modern medicine is based on clinical symptoms of disease. Through earlier identification of individuals at increased risk for disease, preventive strategies could be applied, before the severe stages appear. Preliminary results affirm the feasibility of the project and provide proof-of-concept that LOY-tests can be used for early identification of men with increased risks for these diseases. In addition to improving diagnostics and therapeutics; implementation of LOY-testing could prevent smoking-related disease and reduce the health care costs. In the end, LOY-testing could decrease male mortality rates and possibly eliminate the sex-difference in life expectancy. The project will therefore benefit individual patients as well as healthcare systems and society at large.

1 525 000 €

Start date: 2016-03-01, End date: 2021-02-28

With close to 2000 detected planets, it is striking that we still do not understand how planets form. Their building blocks form in gas disks around young stars, where colliding dust grains form ever-larger aggregates. But this growth is not without limits: larger particles quickly drift towards the star and collide at speeds that shatter them to pieces, long before gravity can bind them together. The mechanisms involved in the assembly and transport of these building blocks remain some of the biggest mysteries of planet formation. Solids in protoplanetary disks evolve differently than the gas, but not independent of it. Observations allow us to directly probe particle growth – the first stage of planet formation. But the gas-solids coupling also enables us to probe the gas disk structure indirectly – just like we cannot see the wind, but we see leaves being moved by it. With this proposal I want to answer some of the key questions of planet formation: (1) What mechanisms drive disk evolution? (2) What role do solids play in the transport of volatiles and the pre-biotic building blocks of life? We will for the first time couple detailed models of the evolution of solids in protoplanetary disks with chemical models on the one side and with hydrodynamical simulations on the other. We aim to derive the unique observable fingerprints of these processes and link those predictions to upcoming observations. With the advent of the ALMA observatory, the prospects of finding these fingerprints are excellent. ALMA will allow us to test our predictions through a wide range of observables at unprecedented sensitivity and resolution, including dust continuum emission, chemical abundance patterns, and isotopic ratios in disks, comets, and our solar system. With our work designed to interpret these observations, we will set the stage for a future understanding of protoplanetary disks and planet formation.

1 435 088 €

Start date: 2017-03-01, End date: 2022-02-28

A thorough understanding of the processes regulating the conversion of gas into stars is key to understand structure formation in the universe and the evolution of galaxies through cosmic time. Despite significant progress over the past years, the properties of the actual dense, star forming gas across normal disk galaxies remain largely unknown. This will be changed with EMPIRE, a comprehensive 500hr large program led by the PI at the IRAM 30m mm-wave telescope. EMPIRE will provide for the first time extended maps of a suite of dense gas tracers (e.g., HCN, HCO+, HNC) for a sample of nearby, star-forming, disk galaxies. By means of detailed analysis, including radiative transfer and chemical modelling, we will constrain a variety of physical quantities (in particular gas densities). We will relate these directly to the local star formation efficiency and to a variety of other dynamical, stellar and local ISM properties from existing pan-chromatic mapping of these galaxies (HI, IR, CO, UV, optical) to answer the question: ``how is star formation regulated across galaxy disks?''. By determining true abundance variations, we will contribute key constraints to the nascent field of galaxy-scale astrochemistry. Detailed comparisons to data for star forming regions in the Milky Way will link core, cloud and galactic scales towards a coherent view of dense gas and star formation. These results will provide an essential anchor point to Milky Way and high redshift observations alike. Analysis, interpretation and modelling of this complex data set requires a team of two postdocs and two PhD students. The PI has demonstrated his ability to successfully lead a research group through his current position as a DFG funded Emmy-Noether group leader. In combination with his widely recognized previous work and his expertise in mm-wave astronomy and ISM/star formation studies, the PI and the proposed group are uniquely positioned to make significant impact during this ERC grant.

1 659 451 €

Start date: 2017-07-01, End date: 2022-06-30

Oligodendrocytes (OL) are glial cells that mediate myelination of neurons, a process that is defective in multiple sclerosis (MS). Although OL precursor cells (OPCs) can initially promote remyelination in MS, this regenerative mechanism eventually fails in progressive MS. OPCs go through several epigenetic states that ultimately define their potential to differentiate and myelinate. OPCs in progressive MS stall in a distinct epigenetic state, incompatible with differentiation and remyelination. We hypothesize that these OPCs regress to an epigenetic state reminiscent of the state of embryonic OPCs, which remain undifferentiated. In this proposal, we aim to uncover the causes behind the remyelination failure upon disease progression in MS. We will determine the epigenetic/transcriptional states of OPCs during development and in MS, using single cell and bulk RNA sequencing and quantitative proteomics. We will further investigate how the interplay between transcription factors (TFs), chromatin modifiers (ChMs) and non-coding RNAs (ncRNAs) contributes to the transition between epigenetic states of OPCs. The results will allow the identification of ChMs and ncRNAs that can modulate these states and thereby control OPC differentiation and myelination. We will use this knowledge to investigate whether we can reverse the epigenetic state of OPCs in MS, in order to promote their differentiation and remyelination. The unique combination of leading-edge techniques such as SILAC coupled with immunoprecipitation and mass-spectrometry, single-cell RNA sequencing, ChIP-Sequencing, among others, will allow us to provide insights into novel epigenetic mechanisms that might be underlying the effects of environmental and lifestyle risk factors for MS. Moreover, this project has the potential to lead to the discovery of new targets for epigenetic-based therapies for MS, which could provide major opportunities for improved clinical outcome of MS patients in the near future.

1 895 155 €

Start date: 2016-09-01, End date: 2021-08-31

Pancreatic islet transplantation is essential for diabetes treatment. Outcome varies due to transplantation site, quality of islets and the fact that transplanted islets are affected by the same challenges as in situ islets. Tailor-making islets for transplantation by tissue engineering combined with a more favorable transplantation site that allows for both monitoring and local modulation of islet cells is thus instrumental. We have established the anterior chamber of the eye (ACE) as a favorable environment for long term survival of islet grafts and the cornea as a natural body window for non-invasive, longitudinal optical monitoring of islet function. ACE engrafted islets are able to maintain blood glucose homeostasis in diabetic animals. In addition to studies in non-human primates we are performing human clinical trials, the first patient already being transplanted. Tissue engineering of native islets is technically difficult. We will therefore apply genetically engineered islet organoids. This allows us to generate i) standardized material optimized for transplantation, function and survival, as well as ii) islet organoids suitable for monitoring (sensor islet organoids) and treating (metabolic islet organoids) insulin-dependent diabetes. We hypothesize that genetically engineered islet organoids transplanted to the ACE are superior to native pancreatic islets to monitor and treat insulin-dependent diabetes. Our overall aim is to create a platform allowing monitoring and treatment of insulin-dependent diabetes in mice that can be transferred to large animals for validation. The objective is to combine tissue engineering of islet cell organoids, transplantation to the ACE, synthetic biology, local pharmacological treatment strategies and the development of novel micro electronic/micro optical readout systems for islet cells. This regenerative medicine approach will follow our clinical trial programs and be transferred into the clinic to combat diabetes.

2 500 000 €

Start date: 2020-01-01, End date: 2024-12-31

Over the next decade, much effort on major astronomical facilities will be dedicated to large-scale surveys of the galaxy population. Their aim is two-fold: understanding the origin and evolution of galaxies and their central supermassive black holes, and clarifying the nature of dark matter, dark energy and the process that produced all cosmic structure. Achieving these goals will require powerful and flexible modelling tools that can simulate galaxy evolution in all viable cosmologies and under a wide variety of assumptions about the governing physical processes. Such capabilities do not currently exist. I propose to develop them through a major expansion of the functionality and scope of the Millennium Simulation archive. New simulations, new theoretical approaches and new web services will allow users to study galaxy formation across the full range of galaxy masses (from dwarf spheroidals to giant cDs). Remote users will be able to change parameters and modelling prescriptions at will, creating virtual surveys of universes with any chosen cosmology and galaxy formation model. Matching to multiwavelength surveys of real galaxies will make it possible to isolate the physical processes driving galaxy evolution, and to characterize the systematic errors that uncertain galaxy formation physics induce in precision estimates of cosmological parameters. Scientific problems where these new capabilities may be decisive in enabling progress include: the role of supermassive black holes in shaping galaxy formation; the origin of diversity in the forms of galaxies and in their nuclear activity; the effects of environment on galaxy structure; the formation history of our own Milky Way; the nature of the first galaxies and their effects on later and more easily observable generations of galaxies; the distribution and nature of dark matter; the origin of all cosmic structure; and the nature of dark energy.

1 830 000 €

Start date: 2010-01-01, End date: 2014-12-31

Stars with more than about ten solar masses dominate galactic ecosystems and understanding the circumstances of their formation is one of the great challenges of modern astronomy. The spectacular HII regions they excite delineate the spiral arms of galaxies such as our own when seen face on making it clear that star formation and Galactic structure are intimately related. We propose to attain a Global View of Star Formation in the Milky Way in a powerful multi-pronged approach. Using VLBI observations of maser sources associated with young protostars, we will measure distances by trigonometric parallax to most of the dominant star forming regions in the Galaxy, which will reveal its spiral structure as well as faithfully represent the luminosity and masses of its constituents. A survey for submillimeter emission from dust, which we are presently pursuing, will deliver the locations of unseen deeply embedded protostars and protoclusters. We plan to combine this data with a comprehensive program to study the gaseous content of the protostellar regions and a very sensitive survey of the Galactic plane with the newly Expanded Very Large Array to find masers and hypercompact HII regions, pinpointing the very centers of the earliest star-forming activity. We also propose to study the infrared emission from more developed massive star clusters, deriving distance with the classic spectro-photometric method, properly calibrated with trigonometric parallaxes, and for the first time adapted to an extensive IR dataset. Our synoptic approach will utilize Europe s premier telescopes including ESO s VLT, the European VLBI Network, the APEX telescope, and ALMA to create a coherent, unique dataset with true legacy value for a global perspective on star formation in our Galaxy.

2 355 079 €

Start date: 2010-05-01, End date: 2015-04-30

Over the past two decades, a data-driven revolution has occurred in our understanding of the origin and evolution of our Universe and the structure within it. During this period, cosmology has evolved from a speculative branch of theoretical physics into precision science at the intersection of gravity, particle- and astrophysics. Despite all we have learned, we still do not understand why the Universe accelerates, and how the structure in the Universe originated. Recent breakthrough research, with leading contributions by the PI of this proposal, has shown that we can make progress on these questions using observations of the large-scale structure and its tracers, galaxies. This opens up a fascinating, new interdisciplinary research field: probing Gravity and Inflation with Galaxies. The goal of the proposed research is to first, probe our theory of gravity, General Relativity, on cosmological scales. Second, it aims to shed light on the origin of the initial seed fluctuations out of which all structure in the Universe formed, by constraining the physics and energy scale of inflation. While seemingly unrelated, the main challenge in both research directions consists in understanding the nonlinear physics of structure formation, which is dominated by gravity on scales larger than a few Mpc. By making progress in this understanding, we can unlock a rich trove of information on fundamental physics from large-scale structure. The research goals will be pursued on all three fronts of analytical theory, numerical simulations, and confrontation with data. With space missions, such as Planck and Euclid, as well as ground-based surveys delivering data sets of unprecedented size and quality at this very moment, the proposed research is especially timely. It will make key contributions towards maximizing the science output of these experiments, deepen our understanding of the laws of physics, and uncover our cosmological origins.

1 330 625 €

Start date: 2016-09-01, End date: 2021-08-31

Acute graft-versus-host disease (GvHD) is the leading cause of the high mortality of patients having undergone allogeneic hematopoietic cell transplantation. A key event in the pathogenesis of GvHD is the injury and loss of epithelial cells in the intestinal tract. The overall goal of GvHDCure is to identify the pathophysiological mechanisms that initiate (1), propagate (2) and maintain (3) GvHD. (1) We found that one of the earliest events during GvHD initiation is infiltration of the intestines by neutrophils. By using transgenic neutrophil cell lines carrying selective gene defects, we will systematically evaluate molecules in neutrophils that are critical for their sensing and effector function during GvHD in combination with novel imaging methods to track bacterial translocation. (2) The molecular programs propagating inflammation-induced epithelial apoptosis, endoplasmic reticulum stress and the sensing of DAMPs in GvHD are not understood. We will isolate enterocytes from GvHD mice to develop a precise quantitative genomic and micro RNA (miR) fingerprint of their death. The connection between ER stress and enterocyte death will be validated in intestinal organoid culture systems and in vivo in an XBP-1 mRNA splicing reporter mouse. In addition, we will make use of our human tissue bank, allowing the efficient genetic screening and verification of regulatory molecular networks in the cells from GvHD patients. (3) Maintenance of GvHD relies on continuous immune cell activation. Based on our miR array and phospho-proteomics data set, we will selectively analyze the role of several miRs and kinases in neutrophils, dendritic cells, T cells and enterocytes for GvHD maintenance by using multiple Cre-lox mice and kinase inhibitors to manipulate GvHD. Via a combination of murine and human studies GvHDCure aims to directly develop individualized therapeutic strategies to interfere with GvHD at multiple levels to make allo-HCT more safe for patients with blood cancer.

1 987 500 €

Start date: 2016-03-01, End date: 2021-02-28

The primary purpose of the cardiovascular system is to drive, control and maintain blood flow to all parts of the body. Despite the primacy of flow, cardiac diagnostics still rely almost exclusively on tools focused on morphological assessment. The objective of the HEART4FLOW project is to develop the next generation of methods for the non-invasive quantitative assessment of cardiac diseases and therapies by focusing on blood flow dynamics, with the goals of earlier and more accurate detection and improved management of cardiac diseases. Recently, a novel moment framework for flow quantification using magnetic resonance imaging (MRI) has been presented which allows for simultaneous measurement of time-resolved, three-dimensional (time + 3D = 4D) blood flow velocity and turbulence intensity. In the HEART4FLOW project, this framework is extended and exploited for assessment of intracardiac blood flow dynamics. A user-friendly quantitative assessment approach is obtained for intracardiac blood flow energetics and wall interaction, as well as stenotic and regurgitant blood flow. Furthermore, the accuracy, measurement time, and robustness of 4D flow MRI acquisition are optimized, allowing its use in large clinical trails. Studying intracardiac blood flow dynamics in patients and healthy subjects at rest and under stress will improve our understanding of the roles of flow dynamics in both health and disease, leading to improved cardiac diagnostics, novel assessments of pharmaceutical, interventional, and surgical therapies, and promoting exploration of new avenues for management of cardiac disorders.

1 430 131 €

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

Diabetes is a degenerative disease affecting millions of persons worldwide. A cure for diabetes depends on replacing the insulin-producing ²-cells in the pancreas that are destroyed by the disease. An attractive strategy to attain this goal is to convert liver adult cells of the same patient into pancreatic ²-cells. The liver and pancreas share many aspects of their early development and are specified in adjacent regions of the endoderm, possibly from a common bipotent progenitor cell. Therefore, conversion of liver to pancreas is conceivable and should imply only few steps backward to a common progenitor and little epigenetic changes. However, how pancreatic versus hepatic fate decision occurs during development is still poorly understood. The aim of this proposal is two fold: to perform lineage analysis, and to study developmental regulators of pancreatic versus hepatic fate decision. We will use new genetic tools, based on the GFP and photoconvertible Kaede fluorescent proteins, to address: i. if the liver and pancreas arise from a common bipotent progenitor cell; ii. to trace in vivo; and iii. molecularly profile the presumptive precursor cell and its descendants in the mouse embryo. Our previous studies have identified target genes of the GATA factors that might act as intrinsic developmental regulators of the pancreatic versus hepatic fate decision. Both intrinsic factors together with extrinsic regulators, such as BMP, will be studied. We will test their potential to promote lineage reprogramming of liver to pancreas using the mouse as well as mouse embryonic stem cells as model systems. Understanding how distinct cell types arise from common multipotent progenitor cells is a major quest in developmental biology. Our findings will elucidate the spatiotemporal mechanisms that control pancreas versus liver fate decision. In addition, they will provide the blueprint for lineage reprogramming of adult hepatic cells to pancreas in diabetes cell-therapy.

1 186 746 €

Start date: 2009-11-01, End date: 2014-10-31

Luminous infrared galaxies (LIRGs) emit most of their bolometric luminosity in the far-infrared. They are mainly powered by extreme bursts of star formation and/or Active Galactic Nuclei (AGNs; accreting supermassive black holes (SMBHs)) in their centres. LIRGs are the closest examples of rapid evolution in galaxies and a detailed study of LIRGs is critical for our understanding of the cosmic evolution of galaxies and SMBHs. Centres of some LIRGs are deeply obscured and unreachable at optical, IR and even X-ray wavelengths. These hidden nuclei therefore represent a largely unexplored phase of the growth of central regions with their SMBHs. Large growth spurts are suspected to occur when the SMBHs are deeply embedded. Obscured AGNs thus can provide new constraints on the AGN duty cycle, give the full range of environments and astrophysical processes that drive the growth of SMBHs, and help to complete the picture of connections between the host galaxy and SMBH. Many dust embedded AGNs are still to be discovered as studies suggest that a significant fraction of SMBHs may be obscured in the local and more distant Universe.
In the HIDDeN project we use mm and submm observational methods to reach behind the curtain of dust in the most embedded centres of LIRGs, allowing us to undertake ground-breaking studies of heretofore hidden rapid evolutionary phases of nearby galaxy nuclei. HIDDeN takes advantage of emerging opportunities to address the nature of near-field, and redshift z=1-2, obscured AGNs/starbursts and their associated molecular inflows and outflows in the context of their evolution and the starburst-AGN connection. In particular we use the ALMA and NOEMA telescopes, supported by JVLA, LOFAR, HST and future JWST observations, to address four interconnected goals: A. Probing the Dusty Interiors of Compact Obscured Nuclei (CONs), B. The cold winds of change - Molecular Outflows from LIRGs and AGNs, C. The Co-Evolution of Starbursts and AGNs and D. Are there hidden CONs at z=1-2

2 496 319 €

Start date: 2018-10-01, End date: 2023-09-30

Understanding the nature and distribution of habitable environments in the Universe is one of the fundamental goals of modern astrophysics. For the life we know, liquid water on the planetary surface is a prerequisite. However, a direct detection of liquid water on exoplanets, and especially on a potentially habitable Earth-size planet, is not yet possible. The existence of water almost certainly implies the presence of atmospheric water vapour which must evaporate under stellar irradiation from a cloud deck or from the surface, together with other related molecules. Therefore, devising sensitive methods to detect hot molecules on exoplanets is of high importance. This proposal develops several exploratory theoretical and observational aspects of precision spectropolarimetry for detecting water vapour and other volatiles on exoplanets and in the inner part of protoplanetary disks. These are new tools for making progress in our understanding which fraction of planets acquires water and how planet formation influences their habitability. As a “double differential” technique, spectropolarimetry has enormous advantages for dynamic range problems, like detection of weak line signals against a large stellar background and exploration at scales beyond the angular resolution of telescopes, which are crucial for both exoplanets and inner disks. Direct detection of polarized spectral lines enables recovering precise orbits of exoplanets (including non-transiting systems) and evaluating their masses as well as potentially their magnetic fields. First applied to hot Jupiters the developed tools will create a firm foundation for future exploration of Earth-like planets with larger telescopes. The same technique applied to planetesimals in the inner disks of young stars yields their orbits, temperature, and chemical composition. These will provide constraints on the formation of a planetary atmosphere in the vicinity of the star and its habitable zone.

2 436 000 €

Start date: 2012-04-01, End date: 2017-03-31