Academy of Sciences of the Czech Republic
Prague, Czech Republic

The Academy of science of the Czech Republic was established in 1992 by the Czech National Council as the Czech successor of the former Czechoslovak Academy of science. The Academy is the leading non-university public research institution in the Czech Republic. It conducts both fundamental and strategic applied research.It has three scientific divisions, namely the Division of Mathematics, Physics, and Earth science, Division of Chemical and Life science, and Division of Humanities and Social science. The Academy currently manages a network of sixty research institutes and five supporting units staffed by a total of 6,400 employees, over one half of whom are university-trained researchers and Ph.D. scientists.The Head Office of the Academy and forty research institutes are located in Prague, the remaining institutes being situated throughout the country. Wikipedia.

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Academy of Sciences of the Czech Republic | Date: 2017-01-11

The present invention relates to a prostate-specific membrane antigen (PSMA)-specific binding protein, wherein the PSMA-specific binding protein is a lipocalin 2 (Lcn2)-derived binding protein and binds to PSMA with a K_(D) of 10 nM or lower. The present invention also relates to a nucleic acid molecule encoding the PSMA-specific binding protein of the invention, a vector comprising said nucleic acid molecule of the invention and a host cell transformed with the vector. Furthermore, the invention relates to a method of producing the PSMA-specific binding protein of the invention, the method comprising culturing the host cell of the invention under suitable conditions and isolating the PSMA-specific binding protein produced. The present invention further relates to a protein conjugate comprising the PSMA-specific binding protein of the invention, or the PSMA-specific binding protein produced by the method of the invention. In addition, the present invention relates to a pharmaceutical or diagnostic composition; to the PSMA-specific binding protein of the invention, the nucleic acid molecule of the invention, the vector of the invention, the host cell of the invention or the PSMA-specific binding protein produced by the method of the invention, for use in therapy and/or diagnosis, and in particular for use in the therapy and/or diagnosis of tumors, Crohns disease and/or neurological diseases.

Stuchlik A.,Academy of Sciences of the Czech Republic
Frontiers in Behavioral Neuroscience | Year: 2014

Mammalian memory is the result of the interaction of millions of neurons in the brain and their coordinated activity. Candidate mechanisms for memory are synaptic plasticity changes, such as long-term potentiation (LTP). LTP is essentially an electrophysiological phenomenon manifested in hours-lasting increase on postsynaptic potentials after synapse tetanization. It is thought to ensure long-term changes in synaptic efficacy in distributed networks, leading to persistent changes in the behavioral patterns, actions and choices, which are often interpreted as the retention of information, i.e., memory. Interestingly, new neurons are born in the mammalian brain and adult hippocampal neurogenesis is proposed to provide a substrate for dynamic and flexible aspects of behavior such as pattern separation, prevention of interference, flexibility of behavior and memory resolution. This work provides a brief review on the memory and involvement of LTP and adult neurogenesis in memory phenomena. © 2014 Stuchlik.

Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 3.87M | Year: 2017

Is there a crisis in the legitimacy of the European Union? That research question is timely and important. Investigating it is also an ideal way of training research leaders of tomorrow to rethink our assumptions about the study of legitimate political order. Whilst, however, the financial crisis has raised new questions about the legitimacy of the EU, existing theories of legitimacy crises are largely based on single-state political systems. New theory is, therefore, needed to understand what would count as legitimacy crises in the case of a non-state political system such as the EU. PLATOs (The Post-Crisis Legitimacy of the EU) ESRs will work together as a team to build new theory from 15 investigations into different standards and actors with whom the EU may need to be legitimate. ESRs will go well beyond the state-of-the-art by building a theory of legitimacy crisis in the EU from a uniquely interdisciplinary understanding of how democracy, power, law, economies and societies all fit together with institutions within and beyond the state to affect the legitimacy of contemporary political order. By developing the analytical tools needed to understand a core predicament in which the EU may both need to develop legitimate forms of political power beyond the state and find those forms of power hard to achieve, PLATO will train ESRs with the conceptual clarity needed to define new research questions at the very frontiers of their disciplines and the methodological skills needed to research those questions. They will also be prepared for careers in the non-academic sector (policy-advice, consulting, civil society, European institutions and expert bodies). PLATOs ambitious cross-university, cross-country and cross-sectoral programme of research training, supervision and secondments will pool resources from a unique network of 9 research-intensive universities and 11 non-academic partners who are themselves key users of state-of-the-art social science research.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: BG-02-2015 | Award Amount: 5.20M | Year: 2016

The overall goal of ClimeFish is to help ensure that the increase in seafood production comes in areas and for species where there is a potential for sustainable growth, given the expected developments in climate, thus contributing to robust employment and sustainable development of rural and coastal communities. The underlying biological models are based on single species distribution and production, as well as multispecies interactions. Forecasting models will provide production scenarios that will serve as input to socio-economic analysis where risks and opportunities are identified, and early warning methodologies are developed. Strategies to mitigate risk and utilize opportunities will be identified in co-creation with stakeholders, and will serve to strengthen the scientific advice, to improve long term production planning and the policy making process. ClimeFish will address 3 production sectors through 16 case studies involving 25 species, and study the predicted effects of 3 pre-defined climate scenarios. For 7 of these cases ClimeFish will develop specific management plans (MPs) coherent with the ecosystem approach and based on a results-based scheme that will allow regulators, fishers and aquaculture operators to anticipate, prepare and adapt to climate change while minimizing economic losses and social consequences. A guideline for how to make climate-enabled MPs will be produced, and published as a low-level, voluntary European standard after a consensus-based open consultation process. As a container for the models, scenarios and MPs ClimeFish will develop the ClimeFish Decision Support Framework (DSF) which also contains the ClimeFish Decision Support System (DSS); a software application with capabilities for what-if analysis and visualization of scenarios. The presence of key international stakeholders in the project will ensure quality and relevance of the project outputs thus ensuring uptake and significant impact also after project end.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SFS-10a-2014 | Award Amount: 8.10M | Year: 2015

European aquaculture production provides direct employment to 80,000 people and a 3-billion annual turnover. Parasites cause severe disease outbreaks and high economic losses in finfish aquaculture. The overarching goal of ParaFishControl is to increase the sustainability and competitiveness of European Aquaculture by improving understanding of fish-parasite interactions and by developing innovative solutions and tools for the prevention, control and mitigation of the major parasites affecting Atlantic salmon, rainbow trout, common carp, European sea bass, gilthead sea bream and turbot. To achieve these objectives, ParaFishControl brings together a multidisciplinary consortium comprising 30 partners possessing world-leading, complementary, cross-cutting expertise and drawn from public and private research organisations, and the aquaculture industry. The consortium has access to excellent research facilities, diverse biological resources including host-parasite models, and state-of-the-art vaccinology, genomic, proteomic and transcriptomic technologies. The project will: 1) generate new scientific knowledge on key fish parasites, including genomics, life-cycle, invasion strategy and host-parasite interaction data, with special emphasis on host immunity, pathogen virulence and immunomodulation, providing a scientific basis for improved prophylaxis; 2) determine the transfer of parasites between farmed and wild host populations; 3) develop a wide range of novel prophylactic measures, including vaccines and functional feeds; 4) provide a range of advanced or alternative treatments for parasitic diseases; 5) develop cost-effective, specific and sensitive diagnostic tools for key parasitic diseases; 6) assess the risk factors involved in the emergence, transmission and pathogenesis of parasitic diseases; 7) map the zoonotic risks due to fish helminths and; 8) provide a catalogue of good husbandry practices to obtain safe and high-quality fish products.

Dholakia K.,University of St. Andrews | Zemanek P.,Academy of Sciences of the Czech Republic
Reviews of Modern Physics | Year: 2010

The light-matter interaction has been at the heart of major advances from the atomic scale right to the microscopic scale over the past four decades. Confinement by light, embodied by the area of optical trapping, has had a major influence across all of the natural sciences. However, an emergent and powerful topic within this field that has steadily merged but not gained much recognition is optical binding: the importance of exploring the optically mediated interaction between assembled objects that can cause attractive and repulsive forces and dramatically influence the way they assemble and organize themselves. This offers routes for colloidal self-assembly, crystallization, and organization of templates for biological and colloidal sciences. In this Colloquium, this emergent area is reviewed looking at the pioneering experiments in the field and the various theoretical approaches that aim to describe this behavior. The latest experimental studies in the field are reviewed and theoretical approaches are now beginning to converge to describe the binding behavior seen. Recent links between optical binding and nonlinearity are explored as well as future themes and challenges. © 2010 The American Physical Society.

Zazimalova E.,Academy of Sciences of the Czech Republic
Cold Spring Harbor perspectives in biology | Year: 2010

Interacting and coordinated auxin transporter actions in plants underlie a flexible network that mobilizes auxin in response to many developmental and environmental changes encountered by these sessile organisms. The independent but synergistic activity of individual transporters can be differentially regulated at various levels. This invests auxin transport mechanisms with robust functional redundancy and added auxin flow capacity when needed. An evolutionary perspective clarifies the roles of the different transporter groups in plant development. Mathematical and functional analysis of elements of auxin transport makes it possible to rationalize the relative contributions of members of the respective transporter classes to the localized auxin transport streams that then underlie both preprogrammed developmental changes and reactions to environmental stimuli.

Stros M.,Academy of Sciences of the Czech Republic
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2010

HMGB proteins are members of the High Mobility Group (HMG) superfamily, possessing a unique DNA-binding domain, the HMG-box, which can bind non-B-type DNA structures (bent, kinked and unwound) with high affinity, and also distort DNA by bending/looping and unwinding. HMGBs (there are four HMGBs in mammals, HMGB1-4) are highly abundant and ubiquitously expressed non-histone proteins, acting as DNA chaperones influencing multiple processes in chromatin such as transcription, replication, recombination, DNA repair and genomic stability. Although HMGB1 is a nuclear protein, it can be secreted into the extracellular milieu as a signaling molecule when cells are under stress, in particular, when necrosis occurs. Mammalian HMGBs contain two HMG-boxes arranged in tandem, share more than 80% identity and differ in the length (HMGB1-3) or absence (HMGB4) of the acidic C-tails. The acidic tails consist of consecutive runs of only Glu/Asp residues of various length, and modulate the DNA-binding properties and functioning of HMGBs. HMGBs are subject to post-translational modifications which can fine-tune interactions of the proteins with DNA/chromatin and determine their relocation from the nucleus to the cytoplasm and secretion. Association of HMGBs with chromatin is highly dynamic, and the proteins affect the chromatin fiber as architectural factors by transient interactions with nucleosomes, displacement of histone H1, and facilitation of nucleosome remodeling and accessibility of the nucleosomal DNA to transcription factors or other sequence-specific proteins. © 2009 Elsevier B.V. All rights reserved.

Palecek E.,Academy of Sciences of the Czech Republic | Bartosik M.,Academy of Sciences of the Czech Republic
Chemical Reviews | Year: 2012

After > 50 years of its existence, electrochemistry of NAs is a booming field, currently aimed at developing DNA sensors and sensing assays. A huge amount of knowledge on NA interactions with electrically charged surfaces summarized in this review makes electrochemistry of NAs potentially useful in various fields of biochemical research. DNA and RNA, as well as their mimetics, such as PNA, are electroactive species, producing oxidation and reduction signals of their bases at some electrodes (sections 3.1 and 3.2). Moreover, these NAs can produce capacitive signals related to their adsorption/desorption behavior (section 3.3). Both the faradaic and capacitive signals reflect changes in the DNA structure under conditions close to physiological; highest sensitivity to small structural changes was observed with mercury and solid amalgam electrodes. Using proper EC methods and ionic conditions, either (a) the secondary changes in the DNA structure at the electrode surface can be eliminated to obtain information about the DNA structure in solution, or (b) structural changes can be induced by prolonged contact of dsDNA with electrically charged surface, SSfollowed by their EC detection. Application of negative charges to the surface-attached DNA may result in the DNA denaturation and eventual strand separation at the electrode surface (section 4.2). At positively charged surfaces, no denaturation was observed and stabilization of DNA at these surfaces was reported. However, it is unclear whether DNA assumes a double-helical structure at surfaces or whether the DNA duplex adopts a ladder-like or some other, more or less unwound structure prior to its opening at negative potentials (section 4.4). Label-free methods (based e.g., on the intrinsic electroactivity of NAs) are simple and convenient, but in many cases DNA labeling offers better sensitivity and other advantages. Covalently bound electroactive labels can be easily introduced in NAs (section 5.2). Some labels (such as ferrocene) can be bound to ODNs during their (usually commercial) synthesis in the organic chemistry laboratories. Os(VIII) complexes can be introduced into DNA, RNA, and PNA by addition to the 5,6- double bond in pyrimidine bases, performed just by mixing the reagent with NA at room temperature. Different labels can be also attached to DNA during its enzymatic synthesis. DNA labeling is particularly important for specific end-labeling of target or reporter probe DNAs. In the recent decade, the NA labeling was greatly influenced by application of nanotechnologies (section 5.3). First papers on NA electrochemistry were published >50 years ago, but for about 30 years DNA electrochemistry was a small field involving handful of laboratories, publishing in average ∼10 papers per year. Starting from 1990, an exponential increase in a number of papers occurred, mounting to >700 papers per year during the recent years (Figure 1). This large increase is related to the progress in genomics and particularly in the Human Genome Project, requiring new methods for parallel DNA nucleotide sequencing. EC methods arrived to this field later than optical methods, but their outlook for practical application appear bright, because their performance is now comparable to optical methods; yet EC methods are simpler, less expensive, easily adaptable for miniaturization and well-suited for decentralized analysis and inclusion into LOC. During the first 30 years, the electrochemistry of NAs dealt mainly with basic EC problems, such as electroactivity and adsorption/desorption of NAs, but also with DNA structure in solution and at interfaces (producing early data on DNA premelting and polymorphy of the DNA double helical structure 138 in agreement with trends in the DNA research in that time). In spite of this orientation, many early steps important in the present development of the EC DNA sensors were done. For example, application of solid carbon electrodes, 139 covalent labeling of DNA, 126-128 invention of DNA-modified electrodes, 125 detection of DNA renaturation 100,102,104 and DNA damage 133,840,841 etc., were published before 1990 (Table 2). The development of EC biosensors for DNA hybridization (nucleotide sequencing) started with rather primitive methods using carbon and gold electrodes in combination with redox indicators (binding preferentially to dsDNA). Alternatively, label-free detection based on guanine oxidation signals at carbon electrodes, or later G oxidation with a mediator at ITO electrodes, was used. At gold electrodes, DNA was attached to the surface via its terminal -SH group, forming a SAM with standing-up DNA molecules. At carbon electrodes, unlabeled probe DNA was lying flatly at the electrode surface. These techniques worked relatively well with synthetic ODN targets. They were, however, mostly poorly efficient in the analysis of real DNA samples. To improve the abilities of EC analysis of DNA in biological matrices, about 10 years ago the DST was proposed, in which the DNA hybridization was performed at one surface (usually magnetic beads, optimized for capturing target DNA or RNA from biological materials) and EC detection of the DNA hybridization was done at another surface, that is, at the detection electrode best suited for the given electrode process (section 5.1). DST offered very high sensitivity and specificity in the analysis of real DNA samples, but it required more manipulation than usual SST or an efficient microfluidic system. In the second half of the 1990s, Barton et al. demonstrated unique charge transfer between methylene blue intercalated in the assembly of 15-20 base pair duplex DNAs and a gold electrode to which the duplex was attached via thiol tether (section 5.6). In the following years, this system was improved and employed in the design of various EC assays including DNA hybridization and single-base mismatches. Recently, similar charge transfer has been shown with 100-mer DNA duplex containing covalently bound Nile Blue redox label. Presence of a single base mismatch attenuated the EC signal similarly as in earlier studies of shorter DNA duplexes. In 2003, a new type of a DNA sensor (called E-DNA sensor) was proposed in Heeger's laboratory, based on a change in the structure of ferrocene-labeled DNA hairpin probe into a linear duplex, resulting from the DNA hybridization, resembling thus the molecular beacons based on optical detection (section 5.5). In the hairpin probe, the ferrocene label was located close to the electrode surface and produced an EC signal. Upon the interaction with complementary target DNA, the hairpin changed into a duplex and the label was moved away from the surface, diminishing the EC signal. Later, this signal-off technique was improved and transformed into a more versatile, signal-on technology. Most of the above techniques are strongly dependent on the nature of the electrode used for the DNA sensing. In the ECPs, this dependence is less strict and the performance of the ECP sensor is more dependent on the nature and way of ECP polymerization. ECP may play a passive role, serving just for DNA immobilization, but it can also directly influence the transduction process, manifested by a change of the ECP conductivity, redox behavior, etc. (section 5.4). In such cases, using electrically neutral PNA as a probe is very convenient, because PNA binding to negatively charged target DNA results in a large, easily detectable change in the electrical properties of the DNA-PNA duplex. Papers on development of the DNA sensors dealing with synthetic ODN targets displayed reasonable performance. Real EC analysis does not, however, work with such ODNs and analysis of genomic DNA sequences mostly requires amplification of tDNA by PCR. Compared to synthetic ODN targets, PCR amplicons are usually longer and may contain some additional substances, such as nucleotides and proteins. A number of EC methods have been developed, suitable for the analysis of PCR-amplified DNA and RNA (section 6.1). Moreover, attempts have been made to use EC analysis in endpoint detection of PCR amplicons (section 6.1.1) and to replace optical detection in real-time PCR by EC detection (section 6.1.3). Analysis of NAs without PCR amplification is much more difficult than the detection of PCR amplicons and represents a challenge. In recent years, significant progress has been done, including analysis of unamplified uropathogen rRNA, as well as messenger and microRNAs (section 6.3), frequently based on combination of EC and biochemical approaches. Analysis of unamplified real NA samples is rather difficult because it has to be done in complex biological matrices, such as cell culture, blood, saliva, or urine and requires very high sensitivities and signal-to-noise ratios. S/N has been recently greatly increased by improved shielding of gold electrode surfaces by binary and ternary SAMs. Also DST has shown good properties in the NA analysis in complex biological matrices. Combination of efficient shielding of the surface (at which tDNA is captured) with sandwich assay using TMB as a substrate for HRP/H 2O 2 oxidation appear now very useful in analysis of PCR-unamplified, biologically relevant NA samples (section 6). Cytosine methylation plays important roles in various diseases, including cancer. Simple DNA hybridization techniques cannot be used to detect methylated cytosine, because both base residues exhibit the same base pairing behavior.

Agency: European Commission | Branch: H2020 | Program: MSCA-IF-EF-RI | Phase: MSCA-IF-2015-EF | Award Amount: 154.72K | Year: 2017

Juvenile hormones (JHs) are lipophilic signals of vital importance to insects and related arthropods, representing the most successful group of animals on our planet. Among species relying on regulation by JH are beneficial pollinators and crustaceans, as well as agricultural pests and disease vectors. Manipulation of JH signaling is a good target for insecticide control. Therefore, knowledge of JH signaling is important both for fundamental science and for practical use. The intracellular JH receptor has been identified, largely through work in the host laboratory, but its action is still poorly understood. Current evidence suggests that activity of this JH receptor is modulated by JH-induced phosphorylation. The objective of this proposal is to identify the phosphorylation target sites and to determine their significance for the JH receptor function. To achieve this goal, the status of amino acid residues potentially phosphorylated in response to JH will be determined using mass spectrometry of the JH receptor protein expressed in insect cell lines. The key residues will be mutated either to prevent phosphorylation or to mimic a constitutively phosphorylated state, and the mutant receptors will be examined for capacity to bind JH, induce JH-response genes, and sustain normal insect development in vivo. The approach thus ranges from protein biochemistry through cell-based assays to developmental genetics employing the Drosophila model. The goals are achievable through the combined expertise of the Applicant, extensively trained in protein chemistry and molecular biology at the top-ranking US universities, and the host laboratory of Dr. Marek Jindra, who is among the leaders in insect developmental endocrinology and JH research in particular. This project will enable the Applicant to fully expand her potential and learn insect developmental genetics while permanently integrating to European science.

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