Požadovaný rozpočet: 1.863.000 EUR

The main scientific objective of the project, ‘Cryo-plasma’, is to study processes of electron-ion recombination in plasma at temperatures 4- 40 Kelvin. Particular attention will be paid to three-body collisional radiative recombination (CRR). The theory predicts for CRR strong negative temperature dependence of rate coefficient. Up to now both, good agreement and serious inconsistency with theory were reported. In general there is lack of direct experimental data to support the theory of CRR and experiments suitable for systematic CRR studies don't exist yet. In order to gain experimental data on CRR, it is proposed to design and build ‘Cryo-trap’ for non-neutral electron/ion plasma. The trap will be modified Penning trap with axial gradient of magnetic field (magnetic mirror like). Cold helium buffer gas will be used to cool trapped plasma. Laser induced reaction technique will used to characterise trapped ions. The ‘Cryo-trap’ will be the first experiment where state selective studies of recombination of externally produced ions in plasma environment will be possible (H+, D+, HD+, ArH+, H2D+, para and ortho H3+, etc). Further advantage of proposed experiment is, that CRR will be studied in relatively weak magnetic field (~0.03 Tesla), so its influence on highly excited intermediate Rydberg states will be minimal. The processes of trapping, storing and cooling of plasma in ‘Cryo-trap’ were already numerically simulated. ‘Cryo-plasma’ is multi-disciplinary project with many novel ideas, which can move frontiers of knowledge on recombination processes. The proposed study of recombination processes in non-neutral cryogenic plasma is connection with antimatter formation, with requirement of data for astrophysics and with other fundamental problems of contemporary physics (e.g. plasma confinement and stability). In the frame of project, ‘Cryo-plasma’, it is proposed to create research team and to establish ‘Cryo-plasma’ laboratory at Charles University in Prague.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 1.168.000 EUR

Combinatorics on words is a branch of mathematics on the frontier of pure mathematics and theoretical computer science. Its fundamental importance for computer science originates from the fact that all computing is a manipulation of strings of symbols, that is, of words. Combinatorics on words is central also for everyday processing of natural languages, be it indexing, text search or grammatical analysis. Clever methods used to manipulate the text, contribute to the speed of such tasks at least as much as the increasing power of computers. Previously unexpected biological application of the field emerged with the discovery of the word-combinatorial structure of DNA and with subsequent research on its properties. Despite an enormous development of the field in past several decades, many fundamental questions remain open. The larger becomes the area of applications, the more challenging are those open problems. ACOMET project is focused on such questions regarding basic properties of word equations. In this respect, it proposes to accomplish two different, but closely related objectives. The first one focuses on research of the size of independent systems of equations, with the intention to obtain upper bounds for such systems. This concerns the ability to reduce vast (even infinite) systems of equations to smaller (and finite) systems guaranteeing the same properties. The second objective focuses on using of all, presently available tools for solving equations in words and unify them into a single software application. This approach will allow to avoid repeated mechanical solving of simple problems often found in the literature and will highlight borders of the contemporary knowledge and thus will allow further focused research in the field of combinatorics on words.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 697.000 EUR

The aim of the proposed research project is discovering new nanomaterials, accurate prediction of their electronic, photonic, magnetic, thermodynamic, kinetic and mechanical properties, understanding their formation, optimization of their preparation, rationalization of the available experimental evidence and planning of new tailored experiments by utilization of the state-of-art theoretical and computational methods ranging from quantum chemical calculations to statistical thermodynamics. New candidates for materials with attractive potential applications will be selected both according to the latest development in the field and on a systematic basis from compounds that have not been thoroughly studied yet and quickly and cheaply screened for the desired properties by computations. Promising systems will be then studied in detail by higher-level methods and accurate predictions of their properties will be done together with providing information important for planning of new experiments. In particular, nanomaterials based on fullerenes, carbon nanotubes, their derivatives and inorganic analogs will be studied with an accent on nanomaterials with applications in nanoelectronics, nanomedicine, photovoltaics and hydrogen storage together with addressing fundamental questions about their formation and production optimization.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 1.267.000 EUR

The aim of the project is development and application of new biotechnological and analytical methods to determination of important biomarkers of serious diseases (cancer, atherosclerosis, dyslipidaemia) with using new trends in HPLC. The research direction will be aimed to new area of Ultra-performance liquid chromatography (UPLC) technique and 2-D chromatography technique (2-D HPLC) – typical analytical methods. These methods have never been used in biomarkers monitoring area. The developed methods will be used for biological active compounds analysis – antioxidants and biomarkers status and its changes during hypolipidemic, cancer therapy and next dideseases. Next aim of the project will be using of new trends in 2-D-chromatography for direct analysis of drugs and biomarkers in biofluids. The new direction of coupling of restricted access materials (RAM) into column-switching systems for on-line sample preparation and biomarkers determination will be tested. The proposed direction of the research borders on two different areas – medicine and analytical chemistry. The project joins these two research branches and successful solution will show high potential in early diagnosis of danger diseases. The main aim of the project will be development and application of new analytical methods in improvement and acceleration of precise diagnosis and in improvement in collaboration of medicine doctors and analytical laboratories.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 699.000 EUR

‘Efficient-Matching’ will perform theoretical and empirical work on matching in labor and marital markets. Given how much personal happiness and satisfaction (or a lack of them) derives from such matches, understanding how matching and search processes operate in these markets is important for economic productivity, broader social welfare, and designing policies and institutions that would enhance these goals. ‘Efficient-Matching’ will build on the existing economic research and will rely on theoretical modeling, experiments, and work with observational data. The proposed agenda has two underlying objectives: (1) to inform future research and policy-making in this area; (2) to produce publications in highly-ranked international journals. ‘Efficient-Matching’ proposes nine different studies in four research areas: (1) positive assortative matching in labor markets and on-the-job learning (theory and experiments); (2) interplay between labor and marital markets (theory); (3) marital regulations, divorce, and remarriage in general equilibrium (theory); (4) non-monotone preferences and the pattern of matching (theory and analysis of field data).

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 1.224.000 EUR

The EVODYPLOID project is designated to address critical gaps in our knowledge of the role of genome duplication (polyploidy) in the genesis and maintenance of plant diversity. While polyploidization is widely acknowledged as a major mechanism of speciation in plants, little is still known about the performance, dynamics, and evolutionary potential of recurrently formed polyploid lineages, which in fact represent cryptic biodiversity at the below-species level. In order to answer challenging questions surrounding genome duplication, we propose to initiate interdisciplinary research at the interface between population biology, ecology, and evolutionary biology. Specifically, we plan to address (i) the evolutionary significance of cryptic diversity (ii) the importance of evolutionary history for actual performance and long-term dynamics of populations of polyploids (iii) the possibilities and limits of evolution of plant life history traits and (iv) the effects of genome duplication per se and post-polyploidization evolution. Cross-disciplinary data integration will provide a new level of understanding of dynamics and consequences of genome duplication under natural conditions. It will serve as a foundation for more competent decisionmaking about biota conservation in a changing world. The main deliverables will be published in the form of research articles in renowned scientific journals and disseminated by means of international conferences, workshops, and scholarly meetings. By coupling of the key researchers’ international expertise with an innovative mode of thinking of PhD. students, the EVODYPLOID project will provide a stimulating and competitive forum for cutting-edge research and education at the European level. This will accelerate professional growth of the investigators and transformation of the research group into an internationally-distinguished consortium of collaborating specialists who will significantly contribute to the advancement of science.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 1.439.000 EUR

Bilirubin is the end product of heme catabolism belonging to the superfamily of tetrapyrrolic compounds that serve multiple biological functions in animals and plants. For many years, bilirubin was thought to have no physiological function other than that of a waste product of heme catabolism, useless at best and toxic at worst. Recent studies, however, have shown that the antioxidant effects of mildly elevated serum bilirubin levels may protect against diseases associated with oxidative stress, such as atherosclerosis, cancer, as well as a number of inflammatory, autoimmune and degenerative diseases. On contrary, markedly elevated serum bilirubin levels may cause severe neurological damage, especially in neonates. Precise molecular mechanisms leading to bilirubin neurotoxicity are however not fully understood yet. Similarly, molecular processes contributing to bilirubin-mediated protection against cancer and atherosclerotic diseases are yet to be clarified. The both mentioned causes prevent the establishment of novel preventive measures. Therefore, the major aim of HEMEDIS is to understand the mechanisms of how the products of heme catabolism affect cellular pathways leading to the both, prevention of atherosclerosis and cancer, as well as bilirubin toxicity. The research project is based on as close interrelationship between classic chemical science (synthesis of labeled bile pigments) and biochemistry of heme catabolic products (rigorous methods often neglected in recent studies) for the understanding of the role of heme catabolic pathway in human diseases. This frontier approach will improve our knowledge with direct implication for proposal of novel diagnostic and therapeutic approaches.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 1.237.000 EUR

The project aim is to provide and analyze alternative geometric representation useful for various real-life applications. Instead of using the simplest possible (often piecewise linear) geometric primitives we intend to exploit more sophisticated descriptions. By high-level representation we generally mean a description of geometrical objects, which ensures some special valuable property (e.g. high smoothness, convexity, existence of rational offsets, etc.). In addition, the key values (e.g. arc-length, curvature, offset position etc.) can be deduced very simply from the coefficients used for the high-evel representation. The construction of high-level representations will start with a geometric analysis of the requirements essential for each type of applications and will be achieved using the tools of algebraic, differential and computational geometry. We believe that by this approach many difficult problems occurring in geometrical applications (e.g. geometrical design, robotics, computer aided manufacturing, data mining, numerical simulation) can be solved.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 1.446.000 EUR

The SACRED project intends to focus on the continuity, development and alteration of religious concepts and the problem of stability and change within the system of ancient Egyptian religion itself, mainly in relation to external (e.g. ecological, political, or socio-ethnical) factors of influence upon it. The project aims to concentrate on the (in)separability of religious ideas, concepts and phenomena from their earthly settings and/or profane contexts, as well as on the mutual relationship between the two. The project will be divided into four main workpackages with individual case-studies which cover cardinal subjects of ancient Egyptian religion and which will be analyzed with respect to their stability, change and development in connection to extra-systematic influences and impacts. This will mainly concern natural changes (as for instance climatic change, extinction of species, alterations in landscape, etc.), the involvement of the state (centralization of the state, internal colonization, accumulation of power), socio-ethnic influences, foreign domination and other extra-systematic influences in these processes. The SACRED project also represents a response to discussions on the introduction of new methods, methodology and untried approaches into Egyptology and related scholarly fields, as well as to the current debate on the problem of change and continuity within ancient (Egyptian) religion and recent unexpected research findings that have put earlier theories and methods into question. The main aim of the project is twofold: to test the benefits and limits of recently debated methods and approaches, and to analyze and understand the evolution of key Egyptian religious concepts and extra-systematic, non-religious or profane-based forms of influence upon the formation, alternation or transmission of religious ideas.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 2.965.000 EUR

The INTELANG project aims at a tight integration of frontier research in Computer Science (especially Artificial Intelligence, Knowledge Representation and Machine Learning) and Computational Linguistics (including spoken language understanding). The main goal of the project is to lay out the theoretical, methodological and algorithmic basis for a future leap in performance in combined Natural Language. Processing (both written and spoken) and Artificial Intelligence systems that have language analysis or generation as one of its major components. The novel and unexplored ideas include, but are not limited to integrated, hybrid (linguistic/statistical) approaches, use of very large spoken and text corpora to automatically discover relations between the linguistic form and cognitive function, and to go beyond the usual sentence -based analysis on all levels of formal specification and representation. Unified approach across languages will be followed. Special attention will be given to the ways the content representation can be used in information extraction, summarization, inferencing, question answering, machine translation, dialog systems and possibly other future applications which inherently need “language understanding” in order to be truly “intelligent”.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 1.295.000 EUR

Modern chemistry experiences a fast development of new reactions with dominance in organometallics and recently also organocatalysis. The massive synthetic progress however greatly foreruns mechanistic studies and the deeper insight is often rather limited. This large unexplored area accordingly challenges pioneering research and formulation of new concepts in chemistry. The present research project uses the most powerful tools of several research disciplines and aims towards the investigation of the elementary steps in organic reactions by means of mass spectrometry (MS) in combination with electrospray ionization (ESI) and quantum chemistry with a particular focus on ion spectroscopy. The research will concentrate on elementary reactions in catalysis, e.g. the interaction of catalysts with substrates or bimolecular reactions of reactant/catalyst complexes. A major innovative contribution consists in applying ion spectroscopy for the structural characterization of reaction intermediates using a newly proposed tandem mass spectrometer with a cooled linear ion trap, which will allow two-photon experiments with IR and UV tunable lasers. The experiments will provide specific information about various intermediates and will help to disentangle even complicated mixtures or isomeric ions. In addition, an innovative experiment is designed, in which bimolecular reactivity of isobaric ions will be studied individually. Kinetics of selected reactions in solution will also be followed by ESI/MS. The combined efforts of these different approaches will provide a comprehensive understanding of the reaction mechanisms and will lead to the formulation of new general concepts in organic and organometallic reactivity.

Žadatel: Univerzita Karlova

Požadovaný rozpočet:1.298.000 EUR

Project ‘Skinbarrier’ focuses on the human skin barrier in health and disease; as well as the modulators of skin barrier function. The term modulators comprises: a) Skin permeation enhancers, i.e. compounds intended to enable transdermal drug delivery, b) Skin barrier repair agents for the treatment of skin diseases, and c) Penetration retardants for prevention of skin absorption of unwanted substances. The general aim of this project is to study the structure-activity relationships and identify the most important variables in compounds modifying the skin permeability, elucidate the behaviour of the most potent ones in the skin, and, consequently, acquire novel highly active, non-toxic and non-irritant skin permeation modulators for potential clinical use. Furthermore, the skin barrier function, particularly the role of the stratum corneum ceramides, will be studied. Our team will be assembled mainly from young researchers, post-docs, and Ph.D. students to have complementary expertise from various fields including medicinal chemistry, dermatology, pharmaceutical technology and biochemistry. The expected results of the ‘Skinbarrier’ project are: a) broadening of the possibilities of transdermal drug delivery with improved patient safety and compliance, b) improving therapy of skin barrier diseases, decreasing the need for corticosteroids, which is particularly important in children, c) decreasing skin absorption of unwanted substances, e.g. decreasing the risk of occupational dermatoses.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 1.973.000 EUR

MULTIPOLY aims to establish novel theoretical concepts and experimental strategies to design new classes of synthetic polymers and biohybrid macromolecules that spontaneously assemble into hierarchically organized multi-compartment nanostructures with pre-defined properties that perform in aqueous environments. The main objective of the project is to establish a leading intellectual platform for the development of the next generation of functional polymer-based nano- structured materials with specific functions, such as: (i) bio nanoreactors and nano-catalytic systems (ii) smart multicompartment nano-containers and nano-sensors for biologically active or toxic molecules and heavy metal ions. These research objectives follow from a profound understanding of systematic relationships between the macromolecular architecture, routes of molecular self- and co-assembly and the properties of resulting supra-molecular and supra-colloidal nano-assemblies. To achieve the critical mass of expertise, I have invited colleagues from the Netherlands, Germany, Russia, Switzerland, Czech Republic and France. Together with them, my aim is to apply a creative, inter-disciplinary and cross-border research approach, by combining macromolecular chemistry with the most advanced methods of structural, dynamics and functional characterization, guided by analytical theory and supported by powerful molecular-realistic numerical simulations. The proposed research concepts will enable the creation of a toolbox for further research in the field. We anticipate the fabrication of various prototypes of novel (bio)functional polymer materials operating in aqueous environments. The work will significantly contribute to advances in the field of sustainable non-toxic bio- and nano-technologies, health-care and environmental monitoring and protection, and last but not least, will support sustainable technologies that will improve the quality of life in the European Union.

Žadatel: Akademie věd ČR

Požadovaný rozpočet: 2.382.000 EUR

Recent findings on microbial cell differentiation, specific distribution within the space, cell-cell interaction and signalling opened new area of investigation, where microorganisms are no more considered simply as individual cells, but as constituents of highly organized communities (colonies, biofilms). Although limited, current knowledge in the field suggests existence of unique processes associated with microbial multicellular life-style, prevalent in natural conditions. MULTIMICROBE asks fundamental questions of how spatiotemporal architecture of yeast multicellular colony develops and how its stress resistance, proliferation and longevity are guaranteed. Specific questions are: i) which signals and regulatory mechanisms trigger and guide colony differentiation resulting in precisely localized cell subpopulations possessing distinctive properties, ii) how subsequent interplay between the subpopulations proceeds, iii) which metabolism is crucial for proper colony population development and longevity, iv) which regulatory pathways concert processes leading to distinct architecture under specific environmental conditions and v) which molecules participate in building up and protection of structured biofilm colonies possessing common features with natural yeast biofilms. In addition to standard molecular and cell biology techniques, we will use specific microscopy together with construction of unique yeast strains and other approaches allowing in situ observation of ongoing processes within the 3-dimensional colony structure. Our results will answer fundamental questions on principles involved in development of “primitive” multicellularity and could bring new hints and ideas for understanding of analogous processes in metazoa. In addition, they will contribute to elucidation of specific properties of biofilms, their enormous resistance and adaptability of their metabolism, which make it difficult to fight against clinical, industrial and environmental biofilms.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 1.399.000 EUR

Teeth are one of the key vertebrate innovations, but their evolutionary origins are still a matter of debate. It is believed that teeth evolved either from skin (ectodermal), or from internal (endodermal) denticles. However, the respective character state cannot be directly determined on fossils and for various reasons neither the embryological studies resolved the dilemma for sure. Thus, though the germlayer derivation of teeth presents a keystone for our understanding of how, from where and how many times teeth have evolved, the reliable information on that matter is still missing. Just recently, we proved with aid of a novel experimental-embryological approach that oral teeth can be of ectoderm, endoderm and even of mixed origin (Nature 2008). The present project proposes to complement that approach with other full-scale analyses including detailed gene-expression data and apply it on a spectrum of vertebrate species in order to reveal whether all teeth are produced by identical developmental-genetic mechanisms. Answering these questions will undoubtedly open new scientific horizons since such information will enable us to decide between major evolutionary hypothesis, rule out whether teeth evolved only once and will directly identify mechanisms of evolutionary change that generated amazing diversity of tooth phenotypes. More substantial understanding of the basic developmental and genetic control of tooth development in a broad comparative context will promote interactions with other European research institutions, will contribute to the excellent research and educational activities carried out in the hosting institution and, last but not least, will facilitate developing tissue engineering approaches for human tooth replacement as well.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 1.725.000 EUR

In recent decade, the applications processing human language have improved tremendously. Many of them left research laboratories and became a part of various consumer products. However, most of them rely on existence of large annotated corpora to "learn" about the language(s). Unfortunately, corpus annotation is a very expensive and time consuming task and it is therefore a great challenge for scientists to look for new ways to achieve a representative and very large set of textual data annotated with linguistic information. In our project, we exploit the capacity of the Internet users who love to play games by offering them on-line interactive entertainment with words, phrases or even the whole documents games that will be fun for the players and at the same time will generate training data needed for corpus-based approaches in natural language processing. The goal of our project is to propose, implement and evaluate an online game-playing system as an alternative way of generating the linguistic data needed by the tasks of automatic coreference resolution, named entity recognition and document labelling. Text summarization and question answering systems are examples of the applications that can directly benefit from such research. PLAYLANG approach will utilize the “Games With a Purpose” methodology originally proposed for image labelling. Applying this methodology to texts is a big challenge for the scientific community, because if it succeeds, it will cause a revolutionary breakthrough in contribution of manually annotated data to tasks of natural language processing in a sense of improving their state-of-the-art performance. The games will be designed independently on language under consideration. The quality of generated data will be controlled in two ways: by comparison to manually annotated data and by their contribution to performance of the tasks of automatic coreference resolution, named-entity recognition, and document labelling.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 1.430.000 EUR

PONT is an interdisciplinary based research project tailored for cooperation of experienced polymer, radio and organic chemists, biochemists and biologists. It focuses on design, synthesis and study of the physicochemical and biological properties of advanced, highly effective polymer anti-cancer drug delivery systems (DDS). The project will take advantage of a synergic combination of the dual or ternary effect of drugs with passive and active targeting for application in the site-specific tumour therapy. This highly innovative combination makes it possible to prepare prodrugs or theragnostics for safe, side-effect reduced and highly-active anti-cancer DDS. The proposed DDS will be a versatile system, based on biodegradable branched, grafted, dendritic and micellar polymers, enabling tailored synthesis and attachment of active molecules to polymer carriers. Therapeutic effect of the DDS will be based mainly on a synergic combination of the cytotoxic and the complementing effect (inhibition of ATP-transporters or angiogenicity, inducing of apoptosis, anti-inflammation) of the drugs after their release in the tumour or ionizing radiation – cytotoxic effect synergy. Passive and active targeting will be obtained by combination of high-molecular-weight polymer structures enabling passive targeting into solid tumours due to the EPR effect and attachment of targeting moiety with specific activity used as the homing device to the solid tumours, endothelial cells of the tumour vasculature or melanoma cells. The proposed highly innovative approach is, naturally, accompanied by a risk of unmet groundbreaking research objectives. To minimize the risk, PI will rearrange, if necessary, the team capacities to concentrate on fundamental or problematic issues related to the project.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 1.855.793 EUR

The primary goal of the project is to popularise cancer research in order to increase the understanding of the scientific process and progress, its critical thought and its social engagement to future generations, mainly in the field of biomedical research, while taking into account new advantages it represents to the society. Activities aimed at popularising science are based on interdisciplinary dialogue integrating a number of scientific fields and various theoretical and methodological approaches. To bring the project into life, following methods will be used: portal, thematic films and documentaries, news from the field of science, PR articles, multimedia DVD, magazines inserts, information flyers and booklets. Furthermore, various events will be organized, such as educational-scientific conferences for general public, formal and informal education (lectures, workshops and presentations for high school and other students, teachers, journalists and other interest groups) and a multimedia exhibition.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 941.000 EUR

The main issue of the project is the relationship between the experience and thinking; which is one of the most important themes in current philosophy. Besides its importance in the theories of mind and cognitive sciences, this problem stays in the centre of the phenomenological philosophy, too. The phenomenology offers one of the most refined and structured elucidations of the given problem. Yet, it is questionable whether the phenomenological conception of experience is still tenable. Does phenomenology really offer an adequate picture of the relationship between the experience and thought? Supposed the answer is negative, we must not simply reject the phenomenology with all its accomplishments. Rather, we should preserve the fundamental phenomenological principle that the thinking must refer to experience, while revising the phenomenological notion of experience. Such a critical revision is in fact the basic task of the proposed project. The project has an interdisciplinary character and the investigators can profit from their divers scientific backgrounds (philosophy, mathematics, psychology, social theory and ethics). This is why the project transgresses the existing scientific fields; it promises to create an original perspective, where new view of human mind can be achieved. Moreover, the results of the project should have an impact on the understanding of experience in psychotherapy, social sciences and ethics.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 1.811.000 EUR

The main goal of this multidisciplinary project is to establish a detailed characterization of the ancient Egyptian state as an example of the earliest complex societies in the history of mankind. RIDER focuses on the development of the Egyptian society by analysing the basic environmental, social, economic, and religious components over a period of more than one thousand years and above all on how the society adjusted to major social, environmental and economic stresses. In doing so, several so called “critical episodes” will be defined, to illustrate the mechanism of each particular “multiplier effect” (a set of individual independently rather insignificant factors which together lead to a completely new set of the characteristics of the society) change by using data and analytical tools of several disciplines integrating Egyptology, Archaeology, Linguistics, Political theology and the Environmental studies. The present project proposes a combination of theoretical and field research of a past complex society in all its principal aspects which can elucidate and clarify some contemporary issues related to modern theories of state and adaptations to various human- and environmentally caused phenomena. We include the concepts of emergence and decline of central institutions, origins of primitive democracy, punctuated equilibrium theory, social and political adjustments to climate change, political theology and study of modern identity building vs. cultural memory. The emergence, development and decline/collapse of the past complex societies and patterns of adaptation to various stressful events provide a major theoretical framework that enables us to better understand adaptation processes of contemporary societies to issues of the same or similar nature (i.e collapse when confronted with environmental stress or dysfunctional state structure, and also stresses brought by challenges to cultural and social identity).

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 1.549.000 EUR

The multimedia databases (MDBs) require specific models and implementation techniques. Despite conventional DBs, the multimedia objects have loosely defined structure and semantics. The query concepts and access methods for MDBs are often based on the notion of similarity, which serves as a ranking function between query and database objects. In this project we focus on four state-of-the-art goals in the area of MDBs: Because the similarity measures are often expensive to compute, there have to be efficient access methods developed, minimizing the CPU costs when querying/indexing a database. The first project goal is a development of efficient access methods allowing a large-scale MDB management supporting metric and non-metric similarities. Second, the current research does consider rather primitive query concepts, like range or kNN queries. In this project we will investigate advanced query types, like re-ranking, metric skylines, metric top-k dominating queries and other multi-queries. Such advanced concepts are necessary nowadays, since the data volumes grow rapidly while the primitive queries lose their expressive power. Third, there exists a gap between the database and domain communities – the domain researchers are often not aware of advanced database techniques. On the other hand, the database researchers often simplify the domain problems just to illustrate the potential impact of their techniques in a particular domain (making just “toy” applications). In this project we aim to disseminate and implant the developments into real domain applications. In particular, we plan to apply the state of-the-art techniques into bioinformatics and medical databases. Finally, we plan to implement the SIRET web engine, a public experimental platform for similarity retrieval of various kinds.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 1.378.000 EUR

The malignancy of cancer is associated with the ability of tumour cells to form metastases. Understanding how cells acquire the capacity for invasion and metastasis has been termed the “last great frontier for exploratory cancer research”. The cells´ capacity for invasion and metastasis is considered to be related with the plasticity of cancel cell invasion. Up to the date, only limited number of studies describing molecular mechanisms inducing MAT/AMT has been published while analysis of mechanisms of mesenchymal amoeboid transition (MAT) or amoeboid mesenchymal transition (AMT) have not been carried out. In order to better understand the plasticity of individual cancer cell invasion, it is critical to identify other proteins involved in MAT and/or AMT. Based on the fact that MAT/AMT can be fully manifested only in a 3D environment, the ITCUP proposes to search for new proteins involved in MAT/AMT in such environment. The ITCUP project aims is to bring a new knowledge on understanding of plasticity of individual cancer cell invasion. There are two objectives that we search to achieve within the proposed project: i) analysis of AMT and MAT in 3D environment and ii) detailed analysis of molecular mechanisms underlying amoeboid invasion. We will achieve these goals by developing a novel tool for proteomic analysis of cells in 3D environment. We expect to provide conclusive evidence on involvement of selected signalling proteins in plasticity of cancer cell invasion through analyzing the results gained from proteomic screens with genetic and advanced microscopical approaches. The project outcomes are of enormous importance given the fact that the signaling molecules involved in MAT/AMT of cancer cells are very likely to become attractive targets for therapeutic intervention. In depth understanding of tumour cell plasticity will subsequently lead to development of tailored treatment of metastasis with respect to particular mode of invasiveness.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 1.574.000 EUR

Proposed project supported an international research team of Urban and Regional Laboratory (URRlab), which serves as European incubator of young talented scientists and PhD students settled at Charles University in Prague. URRlab attempts to retain starting young researchers in academic field and integrate them into a powerful autonomous team, which can successfully compete within global scientific community. Research activities of the team are focused on study of consequences of urban and regional processes in European cities with particular stress on comparative investigation of post-socialist and western cities. Among these processes the crucial roles play commercialisation, gentrification and revitalisation of inner cities, dynamic changes on socialist housing estates, new residential and commercial suburbanisation, growing social segregation, changing patterns of inner and international migration and research of daily mobility and everyday life. Essential asset of the project is a new methodical approach to study urban problems based on combination of qualitative and quantitative research methods, comprehensive empirical (terrain) work and ability to apply scientific outcomes in praxis. Inspiration for novel working style in geography using diagnosis, analysis and treatment is clinical medicine and clinical sociology. The project works-up this specific approach, establishes discipline of clinical geography at the universities and makes bridges between universities and institutions, which can transmit scientific knowledge into practical use.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 2.000.000 EUR

The ‘Nanomotions’ project’s main objective is to study in detail interactions between the Van der Waals molecular crystals, as the potential nanoporous molecular storage media, and small molecular guest species. The research hypothesis of the project is based upon very recent research results proving that molecular crystals of derivatives of calixarenes are able to absorb small molecules such as methane, freon, carbon dioxide, acetylene and finally hydrogen. These molecular crystals, therefore, become completely new class of molecular storage materials. The ambition of ‘Nanomotions’ is to contribute significantly to the understanding of physical behaviour of the guest molecules within of the molecular crystal lattice. Such knowledge is of high value for the crystal engineers searching for the novel storage media for volatile gases, among those, hydrogen being of the primary interest. The major methodology used will be the Nuclear Magnetic Resonance (NMR) that is the current state of the art for studying the dynamic phenomena besides the structural features. We wish to merge two limiting notions – of a rigid “ball-and-stick” type crystal structure and a freely moving gas molecule – into a single picture of a material which is macroscopically rigid but microscopically flexible and moving at various length- and time-scales that will be thoroughly described. The project activities will result into new methods and protocols for determining the dynamic and transport phenomena involved in the guest molecules inclusion to the Van der Waals crystal structures. In order to meet the specified challenges, a new research group will be established at the Charles University in Prague.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 2.268.960 EUR

Sepsis (life-threatening infection) is a major public health problem throughout Europe having wide-reaching socio-economic consequences. In the USA in 1995 it cost $17 billion to treat 751,000 patients with severe sepsis, of whom 28.6% died. Major epidemiological studies have found that sepsis-attributable mortality rates are rising. There is thus a critical need to improve our understanding of the sepsis pathophysiology and to develop innovative and efficacious therapies. The lack of significant advances in the treatment of sepsis has been attributed, among others, to the insufficient preclinical models. The development of complex, dynamic and clinically relevant large animal models of sepsis utilizing new powerful technologies of molecular biology represents a key priority within the field of sepsis research. The specific subject of our project will be (I) development of unique, clinically relevant large animal models of sepsis with high translation potential; (II) using these models to evaluate basic cellular and molecular pathophysiology of sepsis-induced organ damage in early and prolonged sepsis and during the recovery. The aim is to unveil the complex picture of tissue-specific proteomic and mitochondrial changes and to reveal new therapeutic molecular targets and biomarkers; (III) to evaluate new treatment approaches. In the context of chaos therapy, pluripotent strategies (mesenchymal stem cells) versus single-organ treatment (interventions aimed at optimizing heart performance by inhibiting of the I (f) current) will be evaluated using bidirectional vertical character of the research, i.e. from cell cultures to animal models and back. The overall goal is to bring new ground-breaking knowledge from the field of cellular biology that is important both in terms of basic (recognising the fundamental mechanisms of cellular dysfunction) and clinical research (defining new molecular goals, treatment concepts and relevant biomarkers).

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 14.915.941 EUR

Virus infections have been implicated in the pathogenesis of type 1 diabetes: enteroviruses are the chief suspects based on their increased frequency in subjects with recently diagnosed diabetes, and in subjects with islet autoimmunity long before clinical diabetes is diagnosed. However, after over forty years of research, it is still not clear which, if any, of the more than 100 enterovirus genotypes may be causative; moreover, participation of viruses outside the enterovirus genus cannot be excluded. Identification of a causative virus would make it possible to develop a vaccine which could be a breakthrough in type 1 diabetes prevention. The project aims to detect and characterize a virus genotype, group, or sequence motif associated with the development of islet autoimmunity and diabetes in two large Nordic cohorts of high-risk subjects observed from birth: DIPP (Finland) and MIDIA (Norway). Our approach is based on metagenomic next generation sequencing technologies, which are rapidly revolutionizing microbiological studies in various research fields. First, the gut viromes will be characterized from stool samples in order to create a large set of specific virus sequence signatures (unique taxa-specific nucleotide sequences determining the virus type). These signatures will subsequently be sought in blood samples using multiplexed specific ligation-amplification and random amplification, both followed by next generation sequencing. The project includes a strong bioinformatics component which will develop new tools and databases for the characterization of the human virome and its complex role in health and disease. The project's competitive edges are created by the synergistic combination of different research fields, the unique biobanks of two exceptionally large longitudinal cohorts, and our laboratories with extensive experience in virus association studies. It will lead to important new discoveries which could not be reached by any of these groups alone.

Žadatel:  Univerzita Karlova

Požadovaný rozpočet: 900.392 EUR

We hypothesize that insulin resistance underlying a range of diseases is a consequence of a self-propagating cascade of a mitochondrial substrate overload, oxidative damage, mitochondrial dysfunction and failed biogenesis in the skeletal muscle. This vicious cycle can possibly be interrupted by mitochondria-targeted antioxidants and activators of mitochondrial biogenesis. To test this hypothesis, myoblasts and mature muscle fibers will be isolated from biopsy samples obtained from patients in various types of insulin-resistant states (obesity, type 2 diabetes, acute sepsis, protracted critical illness and from ICU survivors 1 year after discharge) and from lean insulin-sensitive age matched controls. These cells will be exposed to different concentrations of glucose, fatty acids and insulin and their anaerobic and aerobic metabolism will be measured by real-time extracellular flux analysis. Insulin sensitivity (insulin-induced labeled 2-deoxyglucose uptake) and oxidative damage of mitochondrial DNA and membrane lipids will be measured in parallel. Human subjects will be tested for whole-body insulin resistance, substrate oxidation and aerobic capacity in order to correlate these parameters with metabolic function of muscle cells in vitro. Lastly, we will use mitochondria-targeted antioxidants and activators of mitochondrial biogenesis to observe their effect on oxidative damage and insulin sensitivity both in vitro in muscle cells and in vivo on rodent models of obesity, type 2 diabetes, sepsis and muscle hypothesize that insulin resistance underlying a range of diseases is a consequence of a self-propagating cascade of a mitochondrial substrate overload, oxidative damage, mitochondrial dysfunction and failed biogenesis in the skeletal muscle. This vicious cycle can possibly be interrupted by mitochondria-targeted antioxidants and activators of mitochondrial biogenesis. test this hypothesis, myoblasts and mature muscle fibers will be isolated from biopsy samples obtained from patients in various types of insulin-resistant states (obesity, type 2 diabetes, acute sepsis, protracted critical illness and from ICU survivors 1 year after discharge) and from lean insulin-sensitive age matched controls. These cells will be exposed to different concentrations of glucose, fatty acids and insulin and their anaerobic and aerobic metabolism will be measured by real-time extracellular flux analysis. Insulin sensitivity (insulin-induced labeled 2-deoxyglucose uptake) and oxidative damage of mitochondrial DNA and membrane lipids will be measured in parallel. Human subjects will be tested for whole-body insulin resistance, substrate oxidation and aerobic capacity in order to correlate these parameters with metabolic function of muscle cells in vitro. Lastly, we will use mitochondria-targeted antioxidants and activators of mitochondrial biogenesis to observe their effect on oxidative damage and insulin sensitivity both in vitro in muscle cells and in vivo on rodent models of obesity, type 2 diabetes, sepsis and muscle weakness.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 2.470.000 EUR

Recent findings on microbial cell differentiation, specific distribution within the space, cell-cell interaction and signalling opened new area of investigation, where microorganisms are no more considered simply as individual cells, but as constituents of highly organised communities (colonies, biofilms). Although limited, current knowledge in the field suggests existence of unique processes associated with microbial multicellular life-style, prevalent in natural conditions. MULTIMICROBE asks fundamental questions of how spatiotemporal architecture of yeast multicellular colony develops and how its stress resistance, proliferation and longevity are guaranteed. Specific questions are: i) which signals and regulatory mechanisms trigger and guide colony differentiation resulting in precisely localized cell subpopulations possessing distinctive properties, ii) how subsequent interplay between the subpopulations proceeds, iii) which metabolism is crucial for proper colony population development and longevity, iv) which regulatory pathways concert processes leading to distinct architecture under specific environmental conditions and v) which molecules participate in building up and protection of structured biofilm colonies possessing common features with natural yeast biofilms. In addition to standard molecular and cell biology techniques, we will use specific microscopy together with construction of unique yeast strains and other approaches allowing in situ observation of ongoing processes within the 3-dimensional colony structure. Our results will answer fundamental questions on principles involved in development of “primitive” multicellularity and could bring new hints and ideas for understanding of analogous processes in metazoa. In addition, they will contribute to elucidation of specific properties of biofilms, their enormous resistance and adaptability of their metabolism, which make it difficult to fight against clinical, industrial and environmental biofilms.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 854.353 EUR

During last years it has become evident that microorganisms do not exist as individual cells under natural settings but organise themselves into multicellular populations (colonies or biofilms) capable of cell-cell interaction, signalling and cell differentiation. Although limited, current knowledge in the field suggests the existence of unique processes associated with a microbial multicellular life-style. YEASTMULTICOL asks fundamental questions of how the spatiotemporal architecture of a multicellular yeast colony develops, which regulatory networks, comprising protein constituents, low molecular signals and effectors, control the differentiation of chronologically aged cells within the colony and how these networks regulate the interplay between subpopulations. Colony differentiation results in cells with a longevity phenotype situated in the upper colony layers that seems to profit from being nourished by a strangled cells in the colony interior. The questions asked here are thus related to topics of cell ageing, stress defence and longevity that are crucial in any organism, including humans. To answer the questions, we will combine the skills and knowledge of biologists and chemists from the three institutions with the aim to set up qualitatively new strategies of chronological ageing investigation. In addition to standard molecular and cellular biology techniques, we will use high-throughput techniques, special microscopy and other approaches allowing the in situ observation of on-going last years it has become evident that microorganisms do not exist as individual cells under natural settings but organise themselves into multicellular populations (colonies or biofilms) capable of cell-cell interaction, signalling and cell differentiation. Although limited, current knowledge in the field suggests the existence of unique processes associated with a microbial multicellular life-style. YEASTMULTICOL asks fundamental questions of how the spatiotemporal architecture of a multicellular yeast colony develops, which regulatory networks, comprising protein constituents, low molecular signals and effectors, control the differentiation of chronologically aged cells within the colony and how these networks regulate the interplay between subpopulations. Colony differentiation results in cells with a longevity phenotype situated in the upper colony layers that seems to profit from being nourished by a strangled cells in the colony interior. The questions asked here are thus related to topics of cell ageing, stress defence and longevity that are crucial in any organism, including humans. To answer the questions, we will combine the skills and knowledge of biologists and chemists from the three institutions with the aim to set up qualitatively new strategies of chronological ageing investigation. In addition to standard molecular and cellular biology techniques, we will use highthroughput techniques, special microscopy and other approaches allowing the in situ observation of on-going processes within the 3-dimensional colony structure.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 1.856.040 EUR

Structural analysis of heterogenous native biomolecular interactions in vivo is hampered by the lack of suitable fast and high throughput methods with appropriate resolution power. The proteomic interactome mass spectrometric (MS) analysis is currently the basis for novel drug screening without the knowledge of the actual interaction landscape, its structure and dynamics. Available sets of X-ray and NMR high-resolution structures are of limited relevance for the true biological importance of high spatiotemporal biomolecule functioning, again with minimal screening power. However, it serves as a solid starting point for computer modeling and comparative structural analysis. A new methodology MS3D is complementary to the existing structural methods employing X-ray and NMR principles. It is a significant development in the niche of MS structural datasets of biomolecular interacting pairs, both from in vitro models and under in vivo native conditions of our transcription factor/DNA response element model, supported by molecular dynamics modeling algorithms. MS DREAM proposal is based on integration of non-traditional progressive techniques of computational biostructure modelling, cutting-edge MS and advanced protein engineering to unique sensitive, fast and high-throughput pipeline for highly effective binding ligand generation. The project has three major aims: 1/ design MS workflow suitable for studies of the steady and dynamic states of protein/nucleic acid interaction and complex formation, 2/development of computational tools for rational pre-design of scaffold protein libraries suitable for high affinity binder (HAB) selection and 3/ highthroughput generation technology to produce HABs able to effectively compete and interfere with protein/nucleic acid interactions. MS DREAM promotes a new research group at the Charles University in Prague employing interdisciplinary non conventional techniques in the field of modern biostructural research.

Žadatel: Univerzita Karlova

Požadovaný rozpočet: 1.998.840 EUR

Modern chemistry experiences a "gold rush" in the field of organocatalysis, which constitutes a part of “green chemistry”, because it promises easier degradable chemicals and friendlier working conditions, compared to the classical processes based on organometallic catalysis. This rapidly developing field, with new catalysts and reactions being reported every week, offers an unexplored area for pioneering research. Formulation of new concepts in organic chemistry requires a multi-disciplinary approach and therefore the presented research project uses the most powerful tools of several research disciplines and aims in the investigation of the elementary steps in organocatalytic reactions by means of mass spectrometry, isotope-labelling experiments and quantum chemistry. The research focuses upon the complexation abilities of the catalysts with substrates and bimolecular reactions of the reactant/catalyst complexes with a second reaction partner. A major innovative impulse consists in using ion-mobility spectrometry in combination with tandem mass spectrometry, which will allow examining the bimolecular reactions in dependence of the shape of the complexes. Such approach will provide a comprehensive survey about the reaction mechanisms and will lead to the formulation of general concepts for the development of more efficient catalytic systems. Moreover, the mode of action of the organocatalysts promises a large potential for a chiral recognition in mass spectrometry. The selective complexation properties of series of organocatalysts will be investigated in order to develop a "chiral test kit" for examining chiral compounds.

Žadatel: Univerzita Karlova