ERC FUNDED PROJECTS

Our tissues are constantly renewed by stem cells. Over time, stem cells accumulate cellular damage that will compromise renewal and results in aging. As stem cells can divide asymmetrically, segregation of harmful factors to the differentiating daughter cell could be one possible mechanism for slowing damage accumulation in the stem cell. However, current evidence for such mechanisms comes mainly from analogous findings in yeast, and studies have concentrated only on few types of cellular damage. I hypothesize that the chronological age of a subcellular component is a proxy for all the damage it has sustained. In order to secure regeneration, mammalian stem cells may therefore specifically sort old cellular material asymmetrically. To study this, I have developed a novel strategy and tools to address the age-selective segregation of any protein in stem cell division. Using this approach, I have already discovered that stem-like cells of the human mammary epithelium indeed apportion chronologically old mitochondria asymmetrically in cell division, and enrich old mitochondria to the differentiating daughter cell. We will investigate the mechanisms underlying this novel phenomenon, and its relevance for mammalian aging. We will first identify how old and young mitochondria differ, and how stem cells recognize them to facilitate the asymmetric segregation. Next, we will analyze the extent of asymmetric age-selective segregation by targeting several other subcellular compartments in a stem cell division. Finally, we will determine whether the discovered age-selective segregation is a general property of stem cell in vivo, and it's functional relevance for maintenance of stem cells and tissue regeneration. Our discoveries may open new possibilities to target aging associated functional decline by induction of asymmetric age-selective organelle segregation.

1 500 000 €

Start date: 2016-05-01, End date: 2021-04-30

Compound semiconductor solar cells are providing the highest photovoltaic conversion efficiency, yet their performance lacks far behind the theoretical potential. This is a position we will challenge by engineering advanced III-V optoelectronics materials and heterostructures for better utilization of the solar spectrum, enabling efficiencies approaching practical limits. The work is strongly motivated by the global need for renewable energy sources. To this end, AMETIST framework is based on three vectors of excellence in: i) material science and epitaxial processes, ii) advanced solar cells exploiting nanophotonics concepts, and iii) new device fabrication technologies. Novel heterostructures (e.g. GaInNAsSb, GaNAsBi), providing absorption in a broad spectral range from 0.7 eV to 1.4 eV, will be synthesized and monolithically integrated in tandem cells with up to 8-junctions. Nanophotonic methods for light-trapping, spectral and spatial control of solar radiation will be developed to further enhance the absorption. To ensure a high long-term impact, the project will validate the use of state-of-the-art molecular-beam-epitaxy processes for fabrication of economically viable ultra-high efficiency solar cells. The ultimate efficiency target is to reach a level of 55%. This would enable to generate renewable/ecological/sustainable energy at a levelized production cost below ~7 ¢/kWh, comparable or cheaper than fossil fuels. The work will also bring a new breath of developments for more efficient space photovoltaic systems. AMETIST will leverage the leading position of the applicant in topical technology areas relevant for the project (i.e. epitaxy of III-N/Bi-V alloys and key achievements concerning GaInNAsSb-based tandem solar cells). Thus it renders a unique opportunity to capitalize on the group expertize and position Europe at the forefront in the global competition for demonstrating more efficient and economically viable photovoltaic technologies.

2 492 719 €

Start date: 2017-01-01, End date: 2021-12-31

The project aims at introducing a paradigm shift in the development of nonlinear photonics with atomically-engineered two-dimensional (2D) van der Waals superlattices (2DSs). Monolayer 2D materials have large optical nonlinear susceptibilities, a few orders of magnitude larger than typical traditional bulk materials. However, nonlinear frequency conversion efficiency of monolayer 2D materials is typically weak mainly due to their extremely short interaction length (~atomic scale) and relatively large absorption coefficient (e.g.,>5×10^7 m^-1 in the visible range for graphene and MoS2 after thickness normalization). In this context, I will construct atomically-engineered heterojunctions based 2DSs to significantly enhance the nonlinear optical responses of 2D materials by coherently increasing light-matter interaction length and efficiently creating fundamentally new physical properties (e.g., reducing optical loss and increasing nonlinear susceptibilities). The concrete project objectives are to theoretically calculate, experimentally fabricate and study optical nonlinearities of 2DSs for next-generation nonlinear photonics at the nanoscale. More specifically, I will use 2DSs as new building blocks to develop three of the most disruptive nonlinear photonic devices: (1) on-chip optical parametric generation sources; (2) broadband Terahertz sources; (3) high-purity photon-pair emitters. These devices will lead to a breakthrough technology to enable highly-integrated, high-efficient and wideband lab-on-chip photonic systems with unprecedented performance in system size, power consumption, flexibility and reliability, ideally fitting numerous growing and emerging applications, e.g. metrology, portable sensing/imaging, and quantum-communications. Based on my proven track record and my pioneering work on 2D materials based photonics and optoelectronics, I believe I will accomplish this ambitious frontier research program with a strong interdisciplinary nature.

2 442 448 €

Start date: 2019-09-01, End date: 2024-08-31

Humans interact with other people throughout their lives. This project aims to demonstrate that the complex social shaping of the human brain can be adequately tackled only by taking a leap from the conven-tional single-person neuroscience to two-person neuroscience. We will (1) develop a conceptual framework and experimental setups for two-person neuroscience, (2) apply time-sensitive methods for studies of two interacting persons, monitoring both brain and autonomic nervous activity to also cover the brain body connection, (3) use gaze as an index of subject s attention to simplify signal analysis in natural environments, and (4) apply insights from two-person neuroscience into disorders of social interaction. Brain activity will be recorded with millisecond-accurate whole-scalp (306-channel) magnetoencepha-lography (MEG), associated with EEG, and with the millimeter-accurate 3-tesla functional magnetic reso-nance imaging (fMRI). Heart rate, respiration, galvanic skin response, and pupil diameter inform about body function. A new psychophysiological interaction setting will be built, comprising a two-person eye-tracking system. Novel analysis methods will be developed to follow the interaction and possible synchronization of the two persons signals. This uncoventional approach crosses borders of neuroscience, social psychology, psychophysiology, psychiatry, medical imaging, and signal analysis, with intriguing connections to old philosophical questions, such as intersubjectivity and emphatic attunement. The results could open an unprecedented window into human human, instead of just brain brain, interactions, helping to understand also social disorders, such as autism and schizophrenia. Further applications include master apprentice and patient therapist relationships. Advancing from studies of single persons towards two-person neuroscience shows promise of a break-through in understanding the dynamic social shaping of human brain and mind.

2 489 643 €

Start date: 2009-01-01, End date: 2014-12-31

The project will create new methodology for identification and interpretation of animal domestication, with a case study pertaining to reindeer domestication among the indigenous Sámi in northern Fennoscandia. Identification of early animal domestication is complicated due to the limited human control over the animals’ life cycles in early stages of domestication, leading to difficulties in interpreting morphological and genetic data, as well as in using traditional concepts and definitions of domestication. These problems are especially pressing in the study of reindeer domestication, characterized by very limited human control over animals. However, understanding reindeer domestication is important to local communities as well as to the scientific community due to central role of human-reindeer relation as a carrier of culture and identity among many peoples, including Sámi of northern Fennoscandia. As a novel approach, we propose a focus on interactional events between humans and animals as indications of domestication taking place. We will create methods aimed at identifying interactional events such as draught use and feeding, between reindeer and humans. The methodological package includes physical activity reconstruction through entheseal changes, pathological lesions and bone cross-sections, and analysis of stable isotopes as indicator of animal diet. These methods will then be applied for archaeological reindeer bone finds and the results will be checked against aDNA data to examine changing human-animal relationships among the Sámi. The project has a potential to break new ground in understanding animal domestication as human-animal interaction, a viewpoint pivotal in today’s human-animal studies. Moreover, the project has potential of methodological breakthroughs and creation of transferable methodology. The results will be relevant to local communities and researchers dealing with domestication, human-animal studies and colonial histories.

1 490 915 €

Start date: 2018-02-01, End date: 2023-01-31

In recent years, genome-wide association studies (GWAS) have discovered hundreds of single nucleotide polymorphisms (SNPs) which are significantly associated with coronary artery disease (CAD). However, the SNPs identified by GWAS explain typically only small portion of the trait heritability and vast majority of variants do not have known biological roles. This is explained by variants lying within noncoding regions such as in cell type specific enhancers and additionally ‘the lead SNP’ identified in GWAS may not be the ‘the causal SNP’ but only linked with a trait associated SNP. Therefore, a major priority for understanding disease mechanisms is to understand at the molecular level the function of each CAD loci. In this study we aim to bring the functional characterization of SNPs associated with CAD risk to date by focusing our search for causal SNPs to enhancers of disease relevant cell types, namely endothelial cells, macrophages and smooth muscle cells of the vessel wall, hepatocytes and adipocytes. By combination of massively parallel enhancer activity measurements, collection of novel eQTL data throughout cell types under disease relevant stimuli, identification of the target genes in physical interaction with the candidate enhancers and establishment of correlative relationships between enhancer activity and gene expression we hope to identify causal enhancer variants and link them with target genes to obtain a more complete picture of the gene regulatory events driving disease progression and the genetic basis of CAD. Linking these findings with our deep phenotypic data for cardiovascular risk factors, gene expression and metabolomics has the potential to improve risk prediction, biomarker identification and treatment selection in clinical practice. Ultimately, this research strives for fundamental discoveries and breakthrough that advance our knowledge of CAD and provides pioneering steps towards taking the growing array of GWAS for translatable results.

1 498 647 €

Start date: 2019-01-01, End date: 2023-12-31

The considerable variability within tissue microenvironments as well as the multiclonality of cancers leads to intratumoral heterogeneity. This increases the probablility of cellular states that promote resistance to therapy and eventually lead to reconstitution of the tumor by treatment-resistant cancer cells, which in some cases have properties of normal tissue stem cells. Wnt signals are important in the maintenance of stem cells in various epithelial tissues, including in lung development and regeneration. We hypothesized that Wnt signals contribute to tumor heterogeneity in genetically engineered KrasG12D; Tp53Δ/Δ (”KP”) mouse lung adenocarcinomas (LUAD). We observed that a subpopulation of LUAD cells exhibited high Wnt reporter activity and had increased tumor forming ability, which could be suppressed by silencing of Wnt signaling pathway components or by small molecule Wnt inhibitors in vitro and in vivo. KP LUAD cells show hierarchical features with two distinct populations, one with increased Wnt reporter activity and another forming a niche that provides the Wnt signal. Lineage-tracing experiments in the autochthonous KP tumors demonstrated that Wnt responder cells have increased tumor propagation ability in vivo. Strikingly, selective ablation of the Wnt responder cells resulted in tumor stasis. CRISPR-based targeting or small molecules targeting Wnt signaling reduced tumor growth and prolonged survival in the autochthonous KP mouse lung cancer model. These results indicate that maintenance of heterogeneity within tumors may be advantageous for the tumor cell population collectively. We propose to elucidate the molecular and cellullar mechanisms that control stem-like and niche cell phenotypes using a combination of novel lentiviral vectors and genetically modified mice in the context of the KP LUAD model. These efforts may lead to novel therapeutic concepts in human lung cancer.

1 972 905 €

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

Thermophotonic (TPX) coolers and generators based on electroluminescent (EL) cooling have the potential to enable a high efficiency replacement for thermoelectric devices. Highly optimized TPX devices can even outperform modern compressor based household refrigerators and heat pumps, enabling a significant reduction in the global energy consumption of cooling and heating. While the EL cooling phenomenon is theoretically well understood, it was only very recently demonstrated for the first time under very small power conditions. Enabling high power EL cooling, however, will require a breakthrough in reducing the losses present in conventional light emitting diodes (LED). iTPX aims to enable this breakthrough by developing an alternative approach to enhance the efficiency of light emission. The approach is based on enclosing the emitter-absorber pair used in TPX in a single semiconductor structure forming an optical cavity. This enhances the light emission rate by an order of magnitude and provides a substantial increase in the efficiency as well as several other technical and fundamental benefits. The main goal of iTPX is to demonstrate high power EL cooling for the first time and to provide quantitative insight on the limitations and possibilities of the cavity-based approach. Recent studies have shown extremely high – over 99 % – internal and external quantum efficiencies of light emission from optically pumped semiconductor structures. This suggests that the material quality of common III-V compound semiconductors is perfectly sufficient for EL cooling if similarly performing electrically injected structures can be fabricated in the single cavity configuration.

1 981 250 €

Start date: 2015-10-01, End date: 2020-09-30

Without written transmission, the communication of any learned topic from ancient and medieval times, from theology and philosophy to medicine, science and history, would be snapped and broken. Transmission relies on the fact of ‘publication’. But what does ‘publishing’ mean in the context of a manuscript culture, in which books were copied slowly and singly by hand? What did it mean to ‘publish’ a book in Western Europe in the Middle Ages? MedPub attempts to understand in breadth and depth, for the first time, the medieval act of publishing. The question it seeks to answer is how did Latin authors publish original works during the period from c. 1000 to 1500. The project’s research hypothesis is that publication strategies were not a constant but were liable to change, and that different social, literary, institutional, and technical milieux fostered different approaches to publishing. The act of publishing, therefore, evolved over time, reacting to changes in the wider world. This is a new proposition and opens a new field of study. Results from the project will make a major contribution to our perception of medieval Latin literature—which is the largest surviving body of evidence for the Middle Ages—and even medieval European societal dynamics. The time-frame, c. 1000–1500, embraces Latin literary culture in its high-medieval maturity and its more complex late-medieval developments, ending with a transitional period characterized by the co-existence of the manuscript book and the printed book and witnessing the emergence in Europe of what was to become modern publishing.

1 497 684 €

Start date: 2017-04-01, End date: 2022-03-31

Energy efficiency and sustainability encourage to develop lightweight materials with excellent mechanical properties, combining also additional functionalities and responses. Therein nature allows inspiration, as e.g. pearl of nacre and silk show extraordinary mechanical properties due to their aligned self-assemblies. However, biological complexity poses great challenges and in biomimetics selected features are mimicked using simpler concepts. Previously artificial nacre has been mimicked by multilayer and sequential techniques and ice-templating. However, concepts for aligned spontaneous self-assemblies are called for scalability. We will develop toughened nacre-inspired materials by templating functionalized polymers on colloidal sheets in suspension, followed by self-assembly by solvent removal. Similarly, we will develop silk-mimetic materials using aligned organic fibrous reinforcements in soft dissipative matrix. Nanofibrillated cellulose will be wet-spun using extrusion into coagulant bath, followed by post drawing, drying and functionalization to allow silk-like fibers with high mechanical properties. In another route, cellulose rod-like whiskers will be decorated with soft functional polymers allowing energy dissipation, followed by alignment and interlinking to mimick silk-assemblies. The colloidal routes allow also new functionalities by using functional polymers, e.g. electroactive and conjugated polymers and nanoparticles. Importantly, redox-active polymers are bound on the colloidal sheets. Incorporating in a planar electrochemical cell with flexible electrodes, electrochemical switching of stiffness is obtained using a small voltage, as the intercolloidal interaction is controlled by the charge state of the redox-active layers. This would allow a new class of material, eg. to interface users and devices. In summary, we present a colloidal self-assembly platform for biomimetic materials with exciting mechanical, functional, and switching properties.

2 296 320 €

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

Many eukaryotes, but not the higher metazoans such as vertebrates or arthropods, possess intrinsic by-pass systems that provide alternative routes for electron flow from NADH to oxygen. Whereas the standard mitochondrial OXPHOS system couples electron transport to proton pumping across the inner mitochondrial membrane, creating the proton gradient which is used to drive ATP synthesis and other energy-requiring processes, the by-pass enzymes are non-proton-pumping, and their activity is redox-regulated rather than subject to ATP requirements. My laboratory has engineered two of these by-pass enzymes, the single-subunit NADH dehydrogenase Ndi1p from yeast, and the alternative oxidase AOX from Ciona intestinalis, for expression in Drosophila and mammalian cells. Their expression is benign, and the enzymes appear to be almost inert, except under conditions of redox stress induced by OXPHOS toxins or mutations. The research set out in this proposal will explore the utility of these by-passes for alleviating metabolic stress in the whole organism and in specific tissues, arising from mitochondrial OXPHOS dysfunction. Specifically, I will test the ability of Ndi1p and AOX in Drosophila and in mammalian models to compensate for the toxicity of OXPHOS poisons, to complement disease-equivalent mutations impairing the assembly or function of the OXPHOS system, and to diminish the pathological excess production of reactive oxygen species seen in many neurodegenerative disorders associated with OXPHOS impairment, and under conditions of ischemia-reperfusion. The attenuation of endogenous mitochondrial ROS production by deployment of these by-pass enzymes also offers a novel route to testing the mitochondrial (oxyradical) theory of ageing.

2 436 000 €

Start date: 2009-04-01, End date: 2015-03-31

The next frontier in photonics is to achieve dynamic and externally tunable materials that allow for real-time, on-demand control over optical responses. Light is in many ways an ideal stimulus for achieving such control, and PHOTOTUNE aims at devising a comprehensive toolbox for the fabrication of light-tunable solid-state photonic structures. We harness light to control light, by making use of photoactuable liquid-crystal elastomers, which display large light-induced deformations through coupling between anisotropic liquid-crystal order and elasticity brought about by the polymer network. We will take liquid-crystal elastomers into a new context by intertwining photomechanics and photonics. Specifically, PHOTOTUNE is built around the following two objectives: (i) Tunable photonic bandgaps and lasing in photoactuable layered structures: The aim is to take photomechanical materials into the scale of optical wavelengths and utilize them in thickness-tunable liquid-crystal elastomer films. Such films will be further integrated into layered structures to obtain photonic crystals and multilayer distributed feedback lasers whose properties can be tuned by light. (ii) Photomechanical control over plasmonic enhancement on nanostructured elastomeric substrates: Fabrication of metal nanostructures on substrates that can contract and expand in response to light comprises a perfect, yet previously unexplored, nanophotonic platform with light-tunable lattice parameters. We will apply such tunable photoelastomeric substrates for surface-enhanced Raman scattering and phototunable nonlinear plasmonics. We expect to present a wholly new technological toolbox for tunable optical components and sensing platforms and beyond: The horizons of PHOTOTUNE are as far-reaching as in studying distance-dependent physical phenomena, controlling the speed of light in periodic structures, and designing actively-tunable optical metamaterials.

1 486 400 €

Start date: 2016-05-01, End date: 2021-04-30

Mitochondrial DNA (mtDNA) encodes several proteins playing key roles in bioenergetics. Pathological mutations of mtDNA can be inherited or may accumulate following treatment for viral infections or cancer. Furthermore, many organisms, including humans, accumulate significant mtDNA damage during their lifespan, and it is therefore possible that mtDNA mutations can promote the aging process. There are no effective treatments for most diseases caused by mtDNA mutation. An understanding of the cellular consequences of mtDNA damage is clearly imperative. Toward this goal, we use the budding yeast Saccharomyces cerevisiae as a cellular model of mitochondrial dysfunction. Genetic manipulation and biochemical study of this organism is easily achieved, and many proteins and processes important for mitochondrial biogenesis were first uncovered and best characterized using this experimental system. Importantly, current evidence suggests that processes required for survival of cells lacking a mitochondrial genome are widely conserved between yeast and other organisms, making likely the application of our findings to human health. We will study the repercussions of mtDNA damage by three different strategies. First, we will investigate the link between a conserved, nutrient-sensitive signalling pathway and the outcome of mtDNA loss, since much recent evidence points to modulation of such pathways as a potential approach to increase the fitness of cells with mtDNA damage. Second, we will explore the possibility that defects in cytosolic proteostasis are precipitated by mtDNA mutation. Third, we will apply the knowledge and concepts gained in S. cerevisiae to both candidate-based and unbiased searches for genes that determine the aftermath of severe mtDNA damage in human cells. Beyond the mechanistic knowledge of mitochondrial dysfunction that will emerge from this project, we expect to identify new avenues toward the treatment of mitochondrial disease.

1 497 160 €

Start date: 2015-04-01, End date: 2020-03-31

The sun provides enough energy in one minute to supply the world's energy needs for one year. The grand challenge is to turn this enormous energy potential into electricity in a cost-efficient way. So far, silicon has been most successful at this – but we are still very far away from what is achievable. One of the major problems, which is currently limiting the state-of-the-art photovoltaic solar cells, is related to the material degradation under sun light. I address this issue from a novel perspective: I study the possibility that the root cause for the degradation is related to the interaction of light with copper ions. The cornerstone of the proposal is to transfer my special knowhow from microelectronics to photovoltaics related to controlling copper behaviour in silicon. My proposal is against the commonly accepted theory, however, it could unveil many mysteries related to the degradation phenomenon. Moreover, if successful, the approach could lead to a rather simple solution in avoiding power loss: implementing charge on the surface to attract the copper ions. In this project I aim at verifying my hypotheses, formulating a new theory regarding the chemical reactions behind the degradation and finally demonstrating a method that allows fabrication of stable yet cheap silicon solar cells having potential for more than 30% power increase.

845 770 €

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

How complex but stereotyped tissues are formed, maintained and regenerated through local growth, differentiation and remodeling is a fundamental open question in biology. Understanding how single cell behaviors are coordinated on the population level and how population-level dynamics is coupled to tissue architecture is required to resolve this question as well as to develop stem cell (SC) therapies and effective treatments against cancers. As a self-renewing organ maintained by multiple distinct SC populations, the epidermis represents an outstanding, clinically highly relevant research paradigm to address this question. A key epidermal SC population are the hair follicle stem cells (HFSCs) that fuel hair follicle regeneration, repair epidermal injuries and, when deregulated, initiate carcinogenesis. The major obstacle in mechanistic understanding of HFSC regulation has been the lack of an in vitro culture system enabling their precise monitoring and manipulation. We have overcome this barrier by developing a method for long-term maintenance of multipotent HFSCs that recapitulates the complexity of HFSC fate decisions and dynamic crosstalk between HFSCs and their progeny. This breakthrough invention puts me in the unique position to investigate how HFSCs self-organize into a network of SCs and progenitors through population-level signaling crosstalk and phenotypic plasticity. This project will uncover the spatiotemporal dynamics of HFSCs fate decisions and establish the role of the niche in this process (Aim1), decipher key gene-regulatory networks and epigenetic barriers that control phenotypic plasticity (Aim2), and discover druggable signaling networks that drive bi-directional reprogramming of HFSCs and their progeny (Aim3). By deconstructing complex tissue-level behaviors at an unprecedented spatiotemporal resolution this study has the potential to transform the fundaments of adult SC biology with immediate implications to regenerative medicine.

1 999 918 €

Start date: 2018-05-01, End date: 2023-04-30

The ultimate goal of this research is to make extremely advanced leap enabling processing of wide variety of ceramic materials at ultra low temperatures denoted as ULTIMATE CERAMICS(200-500 oC). The project has its risks, but advantages like utilization of pure ceramic materials on challenging substrates like plastic and paper could offer novel scientific results as well as business opportunities to European industry. Key issues based on scientific laws of matters forming the basic research methodology to succeed are • intelligent selection and development of starting materials • utilization of nano technology • management of dense and uniform packaging of powder particles • minimization of required activation energy during sintering • management of type, level and rate of diffusion in sintering • microwave sintering There are several reasons why this kind of ULTIMATE CERAMICS can now be seriously research. The main issues are that ano particle silver pastes sinterable at ~ 200 oC have recently become commercially available, and ceramics with nano particle size have been widely on the market. However, taking the high risk, ground-breaking challenge, ultimate novel materials and processes are available. ULTIMATE CERAMICS offer significance novel business opportunities for European industry not available in any other way since ceramic materials are able to perform e.g. as semiconductors, dielectric, non-linear dielectrics, sensors, and electrically or magnetically tunable devices. In the industrial point of view, the main issue is to enable printable structures on paper compatible with nano particle silver electrodes and printed organic materials. It is also obvious that novel scientific results will be created especially when several techniques like e.g. microwave sintering – nano particles – sintering aids –silver electrodes - are combined.

1 933 200 €

Start date: 2012-02-01, End date: 2017-10-31