ERC FUNDED PROJECTS

The deep-sea floor hosts a distinct microbial biome covering 67% of the Earth’s surface, characterized by cold temperatures, permanent darkness, high pressure and food limitation. The surface sediments are dominated by bacteria, with on average a billion cells per ml. Benthic bacteria are highly relevant to the Earth’s element cycles as they remineralize most of the organic matter sinking from the productive surface ocean, and return nutrients, thereby promoting ocean primary production. What passes the bacterial filter is a relevant sink for carbon on geological time scales, influencing global oxygen and carbon budgets, and fueling the deep subsurface biosphere. Despite the relevance of deep-sea sediment bacteria to climate, geochemical cycles and ecology of the seafloor, their genetic and functional diversity, niche differentiation and biological interactions remain unknown. Our preliminary work in a global survey of deep-sea sediments enables us now to target specific genes for the quantification of abyssal bacteria. We can trace isotope-labeled elements into communities and single cells, and analyze the molecular alteration of organic matter during microbial degradation, all in context with environmental dynamics recorded at the only long-term deep-sea ecosystem observatory in the Arctic that we maintain. I propose to bridge biogeochemistry, ecology, microbiology and marine biology to develop a systematic understanding of abyssal sediment bacterial community distribution, diversity, function and interactions, by combining in situ flux studies and different visualization techniques with a wide range of molecular tools. Substantial progress is expected in understanding I) identity and function of the dominant types of indigenous benthic bacteria, II) dynamics in bacterial activity and diversity caused by variations in particle flux, III) interactions with different types and ages of organic matter, and other biological factors.

3 375 693 €

Start date: 2012-06-01, End date: 2018-05-31

The discoveries that the expansion of the universe is accelerating due to an unknown “dark energy” and that most of the matter is invisible, highlight our lack of understanding of the major constituents of the universe. These surprising findings set the stage for research in cosmology at the start of the 21st century. The objective of this proposal is to advance observational constraints to a level where we can distinguish between physical mechanisms that aim to explain the properties of dark energy and the observed distribution of dark matter throughout the universe. We use a relatively new technique called weak gravitational lensing: the accurate measurement of correlations in the orientations of distant galaxies enables us to map the dark matter distribution directly and to extract the cosmological information that is encoded by the large-scale structure. To study the dark universe we will analyse data from a new state-of-the-art imaging survey: the Kilo- Degree Survey (KiDS) will cover 1500 square degrees in 9 filters. The combination of its large survey area and the availability of exquisite photometric redshifts for the sources makes KiDS the first project that can place interesting constraints on the dark energy equation-of-state using lensing data alone. Combined with complementary results from Planck, our measurements will provide one of the best views of the dark side of the universe before much larger space-based projects commence. To reach the desired accuracy we need to carefully measure the shapes of distant background galaxies. We also need to account for any intrinsic alignments that arise due to tidal interactions, rather than through lensing. Reducing these observational and physical biases to negligible levels is a necessarystep to ensure the success of KiDS and an important part of our preparation for more challenging projects such as the European-led space mission Euclid.

1 316 880 €

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

Main goal. We aim to understand the puzzling coexistence of antibiotic-resistant and antibiotic-sensitive species in natural soil environments, using novel quantitative experimental techniques and mathematical analysis. The ecological insights gained will be translated into novel treatment strategies for combating antibiotic resistance. Background. Microbial soil ecosystems comprise communities of species interacting through copious secretion of antibiotics and other chemicals. Defence mechanisms, i.e. resistance to antibiotics, are ubiquitous in these wild communities. However, in sharp contrast to clinical settings, resistance does not take over the population. Our hypothesis is that the ecological setting provides natural mechanisms that keep antibiotic resistance in check. We are motivated by our recent finding that specific antibiotic combinations can generate selection against resistance and that soil microbial strains produce compounds that directly target antibiotic resistant mechanisms. Approaches. We will: (1) Isolate natural bacterial species from individual grains of soil, characterize their ability to produce and resist antibiotics and identify the spatial scale for correlations between resistance and production. (2) Systematically measure interactions between species and identify interaction patterns enriched in co-existing communities derived from the same grain of soil. (3) Introducing fluorescently-labelled resistant and sensitive strains into natural soil, we will measure the fitness cost and benefit of antibiotic resistance in situ and identify natural compounds that select against resistance. (4) Test whether such “selection-inverting” compounds can slow evolution of resistance to antibiotics in continuous culture experiments. Conclusions. These findings will provide insights into the ecological processes that keep antibiotic resistance in check, and will suggest novel antimicrobial treatment strategies.

1 900 000 €

Start date: 2012-09-01, End date: 2018-08-31

"I propose to lead an international observational effort to characterize the population of massive planets, brown dwarf and stellar secondaries orbiting their parent stars with short periods, up to 10-30 days. The effort will utilize the superb, accurate, continuous lightcurves of more than hundred thousand stars obtained recently by two space missions – CoRoT and Kepler. I propose to use these lightcurves to detect non-transiting low-mass companions with a new algorithm, BEER, which I developed recently together with Simchon Faigler. BEER searches for the beaming effect, which causes the stellar intensity to increase if the star is moving towards the observer. The combination of the beaming effect with other modulations induced by a low-mass companion produces periodic modulation with a specific signature, which is used to detect small non-transiting companions. The accuracy of the space mission lightcurves is enough to detect massive planets with short periods. The proposed project is equivalent to a radial-velocity survey of tens of thousands of stars, instead of the presently active surveys which observe only hundreds of stars. We will use an assortment of telescopes to perform radial velocity follow-up observations in order to confirm the existence of the detected companions, and to derive their masses and orbital eccentricities. We will discover many tens, if not hundreds, of new massive planets and brown dwarfs with short periods, and many thousands of new binaries. The findings will enable us to map the mass, period, and eccentricity distributions of planets and stellar companions, determine the upper mass of planets, understand the nature of the brown-dwarf desert, and put strong constrains on the theory of planet and binary formation and evolution."

1 737 600 €

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

In contrast to mammals, newts possess exceptional capacities among vertebrates to rebuild complex structures, such as the brain. Our goal is to bridge the gap in the regenerative outcomes between newts and mammals. My group has made significant contributions towards this goal. We created a novel experimental system, which recapitulates central features of Parkinson’s disease in newts, and provides a unique model for understanding regeneration in the adult midbrain. We showed an unexpected but key feature of the newt brain that it is akin to the mammalian brain in terms of the extent of homeostatic cell turn over, but distinct in terms of its injury response, showing the regenerative capacity of the adult vertebrate brain by activating neurogenesis in normally quiescent regions. Further we established a critical role for the neurotransmitter dopamine in controlling quiescence in the midbrain, thereby preventing neurogenesis during homeostasis and terminating neurogenesis once the correct number of neurons has been produced during regeneration. Here we aim to identify key molecular pathways that regulate adult neurogenesis, to define lineage relationships between neuronal stem and progenitor cells, and to identify essential differences between newts and mammals. We will combine pharmacological modulation of neurotransmitter signaling with extensive cellular fate mapping approaches, and molecular manipulations. Ultimately we will test hypotheses derived from newt studies with mammalian systems including newt/mouse cross species complementation approaches. We expect that our findings will provide new regenerative strategies, and reveal fundamental aspects of cell fate determination, tissue growth, and tissue maintenance in normal and pathological conditions.

1 500 000 €

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

The generation of animals by nuclear transfer demonstrated that the epigenetic state of somatic cells could be reset to an embryonic state, capable of directing the development of a new organism. The nuclear cloning technology is of interest for transplantation medicine, but any application is hampered by the inefficiency and ethical problems. A breakthrough solving these issues has been the in vitro derivation of reprogrammed Induced Pluripotent Stem “iPS” cells by the ectopic expression of defined transcription factors in somatic cells. iPS cells recapitulate all defining features of embryo-derived pluripotent stem cells, including the ability to differentiate into all somatic cell types. Further, recent publications have demonstrated the ability to directly trans-differentiate somatic cell types by ectopic expression of lineage specification factors. Thus, it is becoming increasingly clear that an ultimate goal in the stem cell field is to enable scientists to have the power to safely manipulate somatic cells by “reprogramming” their behavior at will. However, to frame this challenge, we must understand the basic mechanisms underlying the generation of reprogrammed cells in parallel to designing strategies for their medical application and their use in human disease specific research. In this ERC Starting Grant proposal, I describe comprehensive lines of experimentation that I plan to conduct in my new lab scheduled to open in April 2011 at the Weizmann Institute of Science. We will utilize exacting transgenic mammalian models and high throughput sequencing and genomic screening tools for in depth characterization of the molecular “rules” of rewiring the epigenome of somatic and pluripotent cell states. The proposed research endeavors will not only contribute to the development of safer strategies for cell reprogramming, but will also help decipher how diverse gene expression programs lead to cellular specification during normal development.

1 960 000 €

Start date: 2011-11-01, End date: 2016-10-31

CHROMPHYS aims at a breakthrough in our understanding of the solar chromosphere by combining the development of sophisticated radiation-magnetohydrodynamic simulations with observations from the upcoming NASA SMEX mission Interface Region Imaging Spectrograph (IRIS). The enigmatic chromosphere is the transition between the solar surface and the eruptive outer solar atmosphere. The chromosphere harbours and constrains the mass and energy loading processes that define the heating of the corona, the acceleration and the composition of the solar wind, and the energetics and triggering of solar outbursts (filament eruptions, flares, coronal mass ejections) that govern near-Earth space weather and affect mankind's technological environment. CHROMPHYS targets the following fundamental physics questions about the chromospheric role in the mass and energy loading of the corona: - Which types of non-thermal energy dominate in the chromosphere and beyond? - How does the chromosphere regulate mass and energy supply to the corona and the solar wind? - How do magnetic flux and matter rise through the chromosphere? - How does the chromosphere affect the free magnetic energy loading that leads to solar eruptions? CHROMPHYS proposes to answer these by producing a new, physics based vista of the chromosphere through a three-fold effort: - develop the techniques of high-resolution numerical MHD physics to the level needed to realistically predict and analyse small-scale chromospheric structure and dynamics, - optimise and calibrate diverse observational diagnostics by synthesizing these in detail from the simulations, and - obtain and analyse data from IRIS using these diagnostics complemented by data from other space missions and the best solar telescopes on the ground.

2 487 600 €

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

How cells retain, lose, and regain developmental plasticity is poorly understood due to ignorance of the molecular mechanisms regulating gene expression. Each gene is regulated by a unique set of factors and as a consequence the trans-acting factors and cis-acting chromatin modification states regulating a given gene are extremely rare. Transcription is affected by events taking place many thousands of base pairs away from the start, a property enabling developmental and evolutionary plasticity, presumably made possible by DNA looping or translocation of factors along chromatin. Most factors regulating a given gene function at many other genes, complicating interpretation of the consequences of altering the activity of such factors. It is difficult to exclude the possibility that phenotypes are knock-on effects. This could be surmounted if it were possible to observe individual genes in real time in three-dimensional space and to analyse the immediate consequences of altering the activity of regulatory factors. Of these, those capable of inter-connecting DNAs or of translocating large distances along chromatin are of interest. Cohesin is such a factor, composed of three core subunits, a pair of Smc proteins and a kleisin subunit, that interact with each other to form a huge tripartite ring, within which it is thought chromatin fibres are entrapped. In proliferating cells, cohesin’s primary function is to connect sister chromatids during DNA replication until the onset of anaphase, possibly by virtue of co-entrapment within a single ring. However, cohesin is present in most quiescent cells and it is becoming clear that it also regulates gene expression and recombination. This proposal has two goals: To image gene expression on polytene chromosomes and to investigate cohesin’s role during ecdysone-induced transcription. The advantage of this system is that we can use micro-injection of TEV protease to inactivate cohesin. A second goal is to develop the TEV system to

2 421 212 €

Start date: 2012-05-01, End date: 2018-04-30

This proposal concerns the debris discs of nearby stars; ie, discs of asteroids, comets and dust. Such dust can be imaged, providing clues to the underlying planetary system. Debris images have already predicted planets later confirmed in direct imaging. Most debris lies in cold outer (~100AU) regions of planetary systems, but a growing number of stars have hot dust in regions where terrestrial planets are expected (few AU). This proposal aims learn about the planetary systems of nearby stars through study of their debris discs. Specific focus is on the frontier area of characterisation and modelling of dust within planetary systems, which is important for the design of missions to detect habitable planets, a high priority goal for the next decade. The PI has played a significant role in debris disc studies, and proposes to consolidate an independent research team in Cambridge. The proposal covers 3 studies supported by 3 PDRAs. Specific objectives are: 1) Debris disc observations: Carry out survey for cold debris around unbiased sample of nearest 500 stars with Herschel and SCUBA2. Follow-up bright discs with high resolution imaging using ALMA and JWST to characterise sub-structure from planets and search for dust at multiple radii. Pioneer survey for hot dust using polarisation and interferometry. 2) Debris disc modelling: Develop new model to follow the interplay between collisions, radiation pressure, P-R drag, sublimation, disintegration, and dynamical interactions with planets. Use model to consider nature of small particle halos, resonant ring structures formed by terrestrial planets, and level of cometary dust scattered into inner regions. 3) Debris disc origin: Demonstrate constraints placed on planet formation models through studies of dust from Earth-moon forming impacts, effect of planetesimals on late-stage planetary dynamics, population synthesis explaining planets and debris, constraints on primordial size and stirring of debris.

1 497 920 €

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

Cell division underlies the growth and development of all living organisms. Following partitioning of bulk cytoplasmic contents by cleavage furrow ingression, dividing animal cells split by a distinct process termed abscission. Whereas a number of factors required for abscission have been identified in previous studies, it is not known by which mechanism they mediate fission of the intercellular bridge between the nascent sister cells. Here, we will establish correlative workflows of time-lapse imaging, super resolution fluorescence microscopy, electron tomography, and electrophysiological assays to bridge spatial and temporal resolution gaps in the study of abscission. We will further develop computational tools for image-based RNAi screening. With this, we aim to: 1) elucidate how membrane and cytoskeletal dynamics coordinately split the intercellular bridge; 2) uncover the signaling pathways controlling abscission timing. Failure in abscission can lead to aneuploidy and cancer. Elucidating its mechanism and temporal control is therefore of general biological and medical relevance. The computational and correlative imaging methods developed in this project will further provide the research community new possibilities for mechanistic studies in intact cells.

1 500 000 €

Start date: 2012-03-01, End date: 2017-02-28

"The aim of my research project is to build a mathematical model for the quantitative assessment of the effects of demographic changes on economic activity. It is an ambitious project as it involves the integration of the latest developments in demographic and economic models. It is also highly innovative as it proposes an original treatment of demographic uncertainty. Most existing models consider demographics as a deterministic variable and foresee a set of scenarios. At best, the models incorporate demographics as a risk variable and assume that agents know the stochastic process underlying the demographic dynamics. In the present research project, I wish to build a demographic-economic model in which the future demographics are uncertain. This will have three consequences. First, individual decisions are different and depend on the individuals' attitudes towards uncertainty. Second, the aggregation of individual decisions is more complex, especially because of the fact that the latter are not necessarily temporally consistent. Third, the approach to economic policy is renewed. The government is not necessarily perceived as an omniscient being who corrects market dysfunctions, but rather, it is itself under uncertainty and must compromise with the choices made by agents."

1 000 000 €

Start date: 2012-03-01, End date: 2017-02-28

The primary questions that drive the Mars exploration program focus on life. Has the Martian climate ever been favorable for life development? Such scenario would imply a distinct planetary system from today with a magnetic flied able to retain the atmosphere. Where is the evidence of such past climate and intern conditions? The clues for answering these questions are locked up in the geologic record of the planet. The volume of data acquired in the past 15 years by the 4 Martian orbiters (ESA and NASA) reach the petaoctet, what is indecent as regard to the size of the Martian community. e-Mars propose to built a science team composed by the PI, Two post-doctorates, one PhD student and one engineer to exploit the data characterizing the surface of Mars. e-Mars proposes the unprecedented approach to combine topographic data, imagery data in diverse spectral domain and hyperspectral data from multiple orbiter captors to study the evolution of Mars and to propose pertinent landing sites for next missions. e-Mars will focus on three scientific themes: the composition of the Martian crust to constraint the early evolution of the planet, the research of possible habitable places based on evidence of past liquid water activity from both morphological record and hydrated mineral locations, and the study of current climatic and geological processes driven by the CO2 cycle. These scientific themes will be supported by three axis of methodological development: the geodatabase management via Geographic Information Systems (G.I.S.)., the automatic hyperspectral data analysis and the age estimates of planetary surface based on small size crater counts.

1 392 000 €

Start date: 2011-11-01, End date: 2017-10-31

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

The goal of this project is to discover the first galaxies that formed after the Big Bang. The astrophysics of galaxy formation is deeply fascinating. From tiny density fluctuations of quantum mechanical nature believed to have formed during an inflationary period a tiny fraction of a second after the Big Bang during structure slowly formed through gravitational collapse. This process is strongly dependent on the nature of the dominant, but unknown form of matter - the dark matter. In the project proposed here I will study the epoch of first galaxy formation and the subsequent few billion years of cosmic evolution using gamma-ray bursts and Lyman-α (Lyα) emitting galaxies as probes. I am the principal investigator on two observational projects utilizing these probes. In the first project, I will over three years starting October 2009 be using the new X-shooter spectrograph on the European Southern Observatory Very Large Telescope to build a sample of ~100 gamma-ray bursts with UV/optical/near-IR spectroscopic follow-up. The objective of this project is to measure primarily metallicities, molecular content, and dust content of the gamma-ray burst host galaxies. I am primarily interested in the redshift range from 9 to 2 corresponding to about 500 million years to 3 billions years after the Big Bang. In the 2nd project we will use the new European Southern Observatory survey telescope VISTA. I am co-PI of the Ultra-VISTA project that over the next 5 years starting December 2009 will create an ultradeep image (about 2000 hr of total integration time) of a piece of sky known as the COSMOS field. I am responsible for the part of the project that will use a narrow-band filter to search for Lyα emitting galaxies at a redshift of 8.8 (corresponding to about 500 million years after the Big Bang) - believed to correspond to the epoch of formation of some of the very first galaxies.

1 002 000 €

Start date: 2011-11-01, End date: 2016-10-31

Organelles are not randomly organized in the cytoplasm of the cell, but often are orderly arranged in mutual relationships that depend on physical, protein bounds. Understanding the molecular nature of the tethers that regulate relative position and juxtaposition of the organelles is one of the main quests of cell biology, given their functional importance. For example, the juxtaposition between mitochondria and endoplasmic reticulum (ER) has been suggested by us and others to crucially impact on Ca2+ signalling and apoptosis. We recently identified the first structural ER-mitochondrial tether in mitofusin 2 (Mfn2), a pro-fusion mitochondria-shaping protein. A fraction of Mfn2 is also located on the ER regulating its morphology, and acting in trans to tether it to mitochondria. The tethering function of Mfn2 impacts on the transmission of Ca2+ signals between the two organelles and is regulated by the oncosuppressor trichoplein/mitostatin. Mfn2 is likely only one of the tethers, as others exist in yeast. Furthermore, the dynamicity of the ER-mitochondria contact is known, but remains poorly understood. Therefore, a clear picture of the anatomy and pathophsyiology of ER-mitochondrial connection is far from being reached. Here we hypothesize that ER-mitochondrial contacts are crucial specialized hubs of cellular signalling whose architecture is modulated by cellular cues, impacting on integrated signalling cascades and ultimately affecting cellular function. To address this hypothesis we wish to setup a research project that aims at (i) increasing our knowledge on the molecular nature of tethers and modulators of ER-mitochondrial tethers in mammalian cells; (ii) clarifying how mitochondrial and ER function are controlled by the tethering; (iii) addressing how juxtaposition influences complex cellular responses including autophagy and cell death; (iv) elucidating the role of tethering in vivo by generating animal models with defined ER-mitochondrial distance.

1 499 995 €

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

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

Lateral gene transfer (LGT) is the process by which prokaryotes acquire DNA across wide taxonomic boundaries and incorporate it into their genome. Accumulating evidence shows that LGT plays a major role in prokaryote evolution. The biological and evolutionary significance of lateral gene transfer has broad implications for our understanding of microbial biology, not only in terms of evolution, but also in terms of human health. Mechanisms of lateral gene transfer include: transformation, transduction, conjugation, and gene transfer agents. Each of these transfer mechanisms leaves distinct and recognizable molecular footprints in genome sequences. The molecular details of these footprints betray the workings of the corresponding mechanisms in nature, but their relative contributions to the evolution of sequenced genomes have so far not been investigated. By identifying these footprints one can specify and quantify the relative contribution of the different LGT mechanisms during prokaryote genome evolution and thereby uncover more of the biology underlying prokaryote evolution in nature. The goal of this proposal is to quantify those contributions and to bring forth a general computer-based model of prokaryote genome evolution that approximates the underlying evolutionary process far more realistically than phylogenetic trees alone possibly can. Here I propose to apply directed networks to the study of prokaryotic genome evolution in an evolutionary model that allows both for vertical inheritance and for lateral gene transfer events. With methods to identify gene donors, all recent LGTs can be described in a single directed network. This is a fundamentally new, biologically more realistic and evolutionarily more accurate, general computational model of prokaryote genome evolution. Such a model will substantially enrich our ability to understand the process of prokaryote evolution as it is recorded in genomic and metagenomic data.

1 500 000 €

Start date: 2012-07-01, End date: 2018-06-30

Despite significant advance, cancer treatment remains suboptimal. Anatomical and physiological differences between humans and simple model organisms like Drosophila are many and major, and preclude the modelling of key aspects of the disease as it proceeds in vertebrates. However, malignant tumors in vertebrates and flies are made of cells that have derailed from their normal course of development, grow out of control, become immortal, invasive, and kill the host. Moreover, like most solid human tumors, Drosophila malignant tumors display chromosomal instability and copy number variation. In addition, some of them are characterized by the upregulation of germline genes, a distinct feature of certain human cancers. Drosophila tumor models offer an unprecedented opportunity to study these basic malignant traits, which characterize human tumors, in a genetically tractable organism, applying sophisticated genome-wide and comprehensive functional assays at a rate and with a level of detail that are not possible in vertebrates. The goal of this project is twofold: (1) to identify new paths of intervention to inhibit tumor growth, and (2) to determine the origin and function of aneuploidy and changes in gene copy number in malignant growth. We are expectant that the results obtained during the course of this project might eventually have a real impact in human health.

2 406 000 €

Start date: 2012-07-01, End date: 2017-06-30

"Gas accretion and galactic winds are two of the most important and poorly understood ingredients of models for the formation and evolution of galaxies. We propose to take advantage of two unique opportunities to embark on a multi-disciplinary program to advance our understanding of the circumgalactic medium (CGM). We will use MUSE, a massive optical integral field spectrograph that we helped to develop and that will be commissioned on the VLT in 2012, to study the CGM in both absorption and emission. We will use 200 hours of guaranteed time to carry out deep redshift surveys of fields centred on bright z≈3.5 and z≈5 QSOs. This will yield hundreds of faint galaxies (mainly Lyα emitters) within 250 kpc of the lines of sight to the background QSOs, an order of magnitude increase compared to the best existing sample (bright, z≈2.3 galaxies). This will allow us to map the CGM in absorption in 3-D using HI and metal lines and to identify, for the first time, the counterparts to most metal absorbers. MUSE will also enable us to detect Lyα emission from the denser CGM (also using another 300 hours of guaranteed time targeting deep HST fields) and thus to directly explore its connection with galaxies and QSO absorbers. We will use the new supercomputer of the Virgo consortium to carry out cosmological hydro simulations that contain 1-2 orders of magnitude more resolution elements than the largest existing (spatially adaptive) runs. We will use the results of our previous work to guide our choice of parameters in order to obtain a better match to the observed mass function of galaxies. In parallel, we will carry out a complementary program of zoomed simulations of individual galaxies. These will have the physics and resolution to include a cold gas phase and hence to bypass much of the ""subgrid"" physics used in the cosmological runs. Both types of simulations will be used to study the physics of gas flows around galaxies and to guide the interpretation of our observations."

1 496 400 €

Start date: 2012-09-01, End date: 2017-08-31

The study of genetic conflict is developing at an almost explosive rate. The recognition that genes or alleles residing in individuals of the two sexes may have conflicting interests is transforming evolutionary biology and, likewise, conflict between genes showing different modes of transmission may fundamentally affect adaptive evolution. The research proposed here will push the frontiers of genetic conflict research and establish new domains. It is aimed at exploring the novel possibility that conflict between mitochondrial and nuclear genes have far-reaching implications for adaptive evolution and at advancing our understanding of the biological consequences of sexual conflict. The project consists of several interrelated parts and will employ insects as model systems. First, I will assess to what extent genetic variation in fitness is sexually antagonistic and what life history traits contribute to sexually antagonistic variation. Second, I will elucidate the genomics of metabolic rate and measure selection on metabolic phenotypes. Third, I will test whether sexually antagonistic epistatic interactions between mitochondrial and nuclear genes generate conflict over metabolic rate. Fourth, I will test the hypothesis that sexual conflict contribute to the evolution of primary and secondary sexual traits. Fifth, I will shed light on the complicated evolutionary interplay between sexual conflict and mating system evolution. I will employ an innovative research strategy, ‘experimental genomics’, in which genomic data is used to guide experimental evolutionary work with distinct genotypes. The research outlined here will collectively provide an unprecedented wealth of information into the role of genetic conflict in several horizons of adaptive evolution, ranging from DNA sequence evolution over life history evolution to speciation, and will set the standard for a new generation of insightful studies aimed at bridging the gap between phenotypic selection and genomics.

2 497 442 €

Start date: 2012-05-01, End date: 2017-04-30

Long gamma ray bursts (long GRBs) and core-collapse supernovae (CCSNe) are two of the most spectacular explosions in the Universe. They are a focal point of research for many reasons. Nevertheless, despite considerable effort during the last several decades, there are still many fundamental open questions regarding their physics. Long GRBs and CCSNe are related. We know that they are both an outcome of a massive star collapse, where in some cases, such collapse produces simultaneously a GRB and a SN. However, we do not know how a single stellar collapse can produce these two apparently very different explosions. The GRB-SN connection raises many questions, but it also offers new opportunities to learn on the two types of explosions. The focus of the proposed research is on the connection between CCSNe and GRBs, and on the physics of shock breakout. As I explain in this proposal, shock breakouts play an important role in this connection and therefore, I will develop a comprehensive theory of relativistic and Newtonian shock breakout. In addition, I will study the propagation of relativistic jets inside stars, including the effects of jet propagation and GRB engine on the emerging SN. This will be done by a set of interrelated projects that carefully combine analytic calculations and numerical simulations. Together, these projects will be the first to model a GRB and a SN that are simultaneously produced in a single star. This in turn will be used to gain new insights into long GRBs and CCSNe in general. This research will also make a direct contribution to cosmic explosions research in general. Any observable cosmic explosion must go through a shock breakout and a considerable effort is invested these days in large field of view surveys in search for these breakouts. This program will provide a new theoretical base for the interpretation of the upcoming observations.

1 468 180 €

Start date: 2012-01-01, End date: 2017-12-31

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

Adaptation to climate variability and change represents an important challenge for the sustainable development of society. Informing climate-related decisions will require new kinds of information and new ways of thinking and learning to function effectively in a changing climate. Adaptation research requires integration across disciplines and across research methodologies. Currently, we lack the critical understanding of which kinds of knowledge systems can most effectively harness science and technology for long-term sustainable adaptation. This interdisciplinary research programme aims to significantly advance knowledge systems to enable society to adapt effectively to an uncertain climate. The programme is divided into two domains: 1) Understanding climate information needs across society and 2) The social status of techno-scientific knowledge in adaptation to climate change. The whole programme will be applied to the UK context given the sophistication of existing knowledge systems (such as probabilistic climate scenarios) and the progressive climate policy landscape (that requires public authorities to regularly report on adaptation activities). The first objective will be achieved through a targeted comprehensive survey of user needs across UK society. After mapping a selection of diverse adapting organisations, in-depth interviews will be conducted with 70 organisations. The interview protocol will: 1) explore the adaptation context; 2) assess the credibility, legitimacy and saliency of climatic and non-climatic knowledge systems; 3) assess the impact of uncertainty on decision-making; and 4) assess users expectations of what science can deliver. The second domain will use science studies to examine the construction, mutation and use of techno-scientific knowledge in adaptation to climate change. Ethnographic research will be conducted through in-depth interviews with 50 experts working on the UK Climate Projections 09 and the Climate Change Risk Assessment.

1 045 000 €

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

There are two fundamental questions on the interaction of animal species that intrigue me: 1) What ‘knowledge’ do animals have of the behaviour and the ecology of other animal species (heterospecific recognition hypothesis)? 2) Do differences in sensory ability play a role in mediating resource partitioning between coexisting, potentially competing animal species (sensory niche partitioning hypothesis)? The central aim of the proposed project is to tackle these questions where species interactions really happens: out in the field (years 3-5). The model system will be a European community of bat species. Bats are an ideal model system, because they largely live in an acoustic world. Echolocation calls of heterospecific bats and acoustic prey cues can be experimentally manipulated and presented in field playback experiments. The central commitment of this project is to study animal behaviour using an experimental and hypothesis driven approach. To reconcile aim and commitment, I want to develop (year 1-2) automated experimental stations (AES) that can be deployed in the field. These stations will autonomously interact with wild animals, run individualized experiments and gather high-quality data for hypothesis testing. A key element will be a loudspeaker array that for the first time can realistically simulate moving sound sources (echolocating bats or prey insects) in the field. The proposal thus strives to answer ecological and evolutionary questions at a new level by developing and employing new technical apparatus, which will remain available for future applications beyond this project. The project will be hosted by the Max Planck Institute for Ornithology in Seewiesen, Germany, where I will benefit from a world-class, stimulating research environment. Field work will be conducted in Bulgaria in cooperation with Bulgarian colleagues and students.

405 672 €

Start date: 2012-01-01, End date: 2014-02-28