The PRINTS database: a fine-grained protein sequence annotation and analysis resource—its status in 2012

The PRINTS database, now in its 21st year, houses a collection of diagnostic protein family ‘fingerprints’. Fingerprints are groups of conserved motifs, evident in multiple sequence alignments, whose unique inter-relationships provide distinctive signatures for particular protein families and structural/functional domains. As such, they may be used to assign uncharacterized sequences to known families, and hence to infer tentative functional, structural and/or evolutionary relationships. The February 2012 release (version 42.0) includes 2156 fingerprints, encoding 12 444 individual motifs, covering a range of globular and membrane proteins, modular polypeptides and so on. Here, we report the current status of the database, and introduce a number of recent developments that help both to render a variety of our annotation and analysis tools easier to use and to make them more widely available

Functional characterization of alternative splice variants of the Drosophila GATA transcription factor serpent containing either one or two zinc finger domains

Les facteurs de transcription GATA jouent un rôle crucial dans divers processus de développement chez les animaux bilatéraux. Chez les mammifères, six facteurs GATA sont présents et ils jouent des rôles essentiels dans différents tissus tels que le sang, l'intestin, le foie et les gonades. Les protéines GATA possèdent deux domaines hautement conservés, les doigts de zinc N-terminal et C-terminal. Le doigt C-terminal reconnaît le motif consensus de liaison à l'ADN GATA, tandis que le doigt N-terminal stabilise la fixation aux séquences palindromiques d'ADN et permet leur interaction avec les cofacteurs de la famille Friend Of GATA (FOG). Les mutations des doigts de zinc GATA sont associées à un vaste éventail de maladies humaines dont la gravité dépend du gène GATA affecté et de la position de la mutation dans les doigts de zinc. De nombreuses études ont démontré le haut niveau de similarités moléculaires et fonctionnelles existant entre les mouches et les humains. La drosophile possède cinq facteurs GATA contenant un ou deux doigts de zinc, dont les séquences sont presque identiques à celles des doigts de zinc canoniques des vertébrés. Parmi eux, le facteur GATA de la drosophile Serpent (Srp) est requis pour la formation des cellules sanguines, de l'intestin et du corps gras ainsi que pendant l'ovogenèse. Dans tous ces tissus, deux isoformes de Srp sont générées par un événement d'épissage alternatif donnant naissance à des protéines contenant soit les deux doigts de zinc (N- et C-terminal, d'où le nom de cette isoforme : SrpNC) ou uniquement le doigt de zinc C-terminal (SrpC). Dans un travail précédent, notre équipe a montré que SrpC et SrpNC activent certains gènes cibles de manière similaire mais aussi elles en régulent d'autres différemment. En plus, l'interaction entre SrpNC et son cofacteur FOG, U-shaped, est responsable de certaines mais pas de toutes les activités distinctes de SrpC et SrpNC. Le but de cette étude est de fournir une investigation génétique approfondie des rôles fonctionnels différentiels possibles des isoformes Srp au cours du développement de la drosophile. En utilisant la technologie CRISPR/Cas9, nous avons généré deux lignées de mouches mutantes invalidées soit pour SrpC ou pour SrpNC. En outre, nous avons produit une troisième lignée de mouche mutante dans laquelle nous avons spécifiquement introduit dans le doigt de zinc N-terminal de Srp une mutation ponctuelle qui modifie son interaction avec U-shaped. L'analyse de ces mutants a révélé que les deux isoformes régulent d'une manière redondante la transcription d'un ensemble commun de gènes au cours du développement intestinal ainsi que de quelques gènes impliqués dans l'hématopoïèse précoce. Étonnamment, les mouches dépourvues de SrpNC (isoforme contenant deux doigts de zinc comme les facteurs GATA des mammifères) sont viables, montrant que cette isoforme est dispensable pour la plupart des processus de développement contrôlés par Srp. Néanmoins, SrpNC semble être spécifiquement nécessaire pour le maintien de l'homéostasie des cellules sanguines et pour la fertilité des mouches. En outre, la perturbation de l'interaction de Srp et de son cofacteur FOG U-shaped équivaut à la perte complète de l'isoforme SrpNC, montrant que SrpNC forme un complexe avec U-shaped pour assurer ses fonctions. En revanche, notre approche génétique a révélé que l'isoforme SrpC est essentielle pour la viabilité et le développement du corps gras, suggérant que cette isoforme régule différents programmes développementaux par rapport à SrpNC. Dans l'ensemble, nos résultats révèlent une plus grande flexibilité fonctionnelle jouée par les doigts de zinc GATA pour remplir leurs nombreux rôles tout au long du développement. En outre, ce travail illustre que, comme la duplication du génome chez les vertébrés, l'épissage alternatif fournit une stratégie efficace pour promouvoir la sous-fonctionnalisation et générer la diversité fonctionnelle des facteurs GATA chez les invertébrés.GATA transcription factors play crucial roles in various developmental processes throughout bilaterian animals. In mammals, six GATA factors are present and they play essential functions in different tissues such as the blood, the gut, the liver and the gonads. GATA proteins have two highly conserved domains, the N-terminal and the C-terminal zinc fingers. The C-terminal finger recognizes GATA DNA-binding consensus motif, while the N-terminal finger stabilizes fixation to DNA palindromic sequences and allows their interaction with cofactors of the Friend Of GATA (FOG) family. GATA zinc finger mutations are associated to a vast panel of human diseases whose severity depends on the affected GATA gene and on the position of the mutation in the zinc fingers. Numerous studies have demonstrated the high level of molecular and functional similarities existing between flies and humans. Drosophila melanogaster has five GATA factors containing either one or two zinc fingers, whose sequences are almost identical to those of the canonical zinc fingers of vertebrates. Among them, the Drosophila GATA factor Serpent (Srp) is required for the formation of blood cells, gut and fat body as well as during oogenesis. In all these tissues, two isoforms of Srp are generated through an alternative splicing event giving rise to proteins containing either both zinc fingers (N- and C-terminal, hence the name of this isoform: SrpNC) or only the C-terminal zinc finger (SrpC). In a previous work, our team has shown that SrpC and SrpNC activate some genes in a similar manner but also they regulate others differently. Moreover, interaction between SrpNC and its cofactor FOG, U-shaped, is responsible for some but not all aspects of the distinct activities of SrpC and SrpNC. The purpose of this study is to provide a deep genetic investigation of possible differential functional roles of Srp isoforms during Drosophila development. Using CRISPR/Cas9 technology, we generated two mutant fly lines deleted either of SrpC or of SrpNC. In addition, we produced a third mutant fly line in which we specifically introduced into the N-terminal zinc finger of Srp a single point mutation that alters its interaction with U-shaped. Analysis of these mutants revealed that both isoforms regulate redundantly the transcription of a common set of genes during gut development as well as few genes involved during early hematopoiesis. Surprisingly, flies devoid of SrpNC (isoform containing two-zinc fingers as the mammalian GATA factors) are viable, showing that this isoform is dispensable for most of the developmental processes controlled by Srp. Nonetheless, SrpNC appears to be specifically required in the maintenance of blood cell homeostasis and for fly fertility. Furthermore, disrupting the interaction of Srp and its FOG cofactor U-shaped is equivalent to the complete loss of the isoform SrpNC, showing that SrpNC forms a complex with U-shaped to ensure its functions. In contrast, our genetic approach unraveled that SrpC isoform is essential for viability and fat body development, suggesting that this isoform regulate different developmental programs compared to SrpNC. Altogether, our results reveal a greater functional flexibility played by the GATA zinc fingers to fulfil their many roles throughout development. Also, this work illustrates that, like genome duplication in vertebrates, alternative splicing provides an efficient strategy to promote subfunctionalization and generate GATA functional diversity in invertebrates

Annual Report 2014 - Institute of Resource Ecology

The Institute of Resource Ecology (IRE) is one of the eight institutes of the Helmholtz-Zentrum Dresden – Rossendorf (HZDR). The research activities are mainly integrated into the program “Nuclear Waste Management, Safety and Radiation Research (NUSAFE)” of the Helmholtz Association (HGF) and focused on the topics “Safety of Nuclear Waste Disposal” and “Safety Research for Nuclear Reactors”. Additionally, various activities have been started investigating chemical and environmental aspects of processing and recycling of strategic metals, namely rare earth elements. These activities are located in the HGF program “Energy Efficiency, Materials and Resources (EMR)”. Both programs, and therefore all work which is done at IRE, belong to the research sector “Energy” of the HGF. The research objectives are the protection of humans and the environment from hazards caused by pollutants resulting from technical processes that produce energy and raw materials. Treating technology and ecology as a unity is the major scientific challenge in assuring the safety of technical processes and gaining their public acceptance. We investigate the ecological risks exerted by radioactive and nonradioactive metals in the context of nuclear waste disposal, the production of energy in nuclear power plants, and in processes along the value chain of metalliferous raw materials. A common goal is to generate better understanding about the dominating processes essential for metal mobilization and immobilization on the molecular level by using advanced spectroscopic methods. This in turn enables us to assess the macroscopic phenomena, including models, codes, and data for predictive calculations, which determine the transport and distribution of contaminants in the environment

Annual Report 2021 - Institute of Resource Ecology

The Institute of Resource Ecology (IRE) is one of the eight institutes of the Helmholtz-Zentrum Dresden–Rossendorf (HZDR). Our research activities are mainly integrated into the program “Nuclear Waste Management, Safety and Radiation Research (NUSAFE)” of the Helmholtz Association (HGF) and focus on the topics “Safety of Nuclear Waste Disposal” and “Safety Research for Nuclear Reactors”. The program NUSAFE, and therefore all work which is done at IRE, belong to the research field “Energy” of the HGF. IRE conducts applied basic research to protect humans and the environment from the effects of radioactive radiation. For this purpose, we develop molecular process understand-ing using state-of-the-art methods of microscopy, spectroscopy, diffraction, numerical simulation, theoretical chemistry and systems biology. We implement this in a cross-institutional research environment at the HZDR. Our active interdisciplinarity combines radiochemistry, geosciences and biosciences as well as materials science and reactor physics. We provide knowledge that is applied in particular to reactor and repository safety as well as in radioecology. We achieve this goal with a unique infrastructure comprising chemical and biological laboratories as well as hot cells in corresponding radiation and biology safety laboratories in Dresden, Leipzig and Grenoble. In Grenoble, at the European Synchrotron Radiation Facility (ESRF), the institute operates a beamline with four experimental stations for continuously advanced X-ray spectroscopy and diffraction of radio-active samples, which is also available to external users

Dietary Practices, Socioeconomic Status, and Social Mobility at Teotihuacan, Mexico

abstract: This project investigates social mobility in premodern states through a contextualized program of isotopic research at the archaeological site of Teotihuacan, Mexico. Due to the lack of a concrete methodology that can be used to recover information concerning rates of social mobility from archaeological remains, many traditional archaeological models either ignore social mobility or assume that boundaries between socioeconomic strata within archaic states were largely impermeable. In this research, I develop a new methodological approach to the identification of socially mobile individuals in the archaeological record based on changes in the diet across the lifecourse that can be detected through isotopic paleodietary indicators. Drawing upon cross-cultural research surrounding the relationship between diet and socioeconomic status and established methodologies in the biogeochemical analysis of human remains, this methodological approach provides a basis for broader comparative studies evaluating the nature of social mobility within archaic states. I then test the practical application of this methodology by applying it to a mortuary sample including individuals from distinctive socioeconomic groups from the pre-Hispanic city of Teotihuacan, Mexico. The study recovers and uses the dietary isotope ratios within bone and tooth samples from 81 individuals buried throughout the city 1) to define the dietary correlates of wealth and status at Teotihuacan and 2) to identify individuals displaying lifetime dietary changes consistent with changes in socioeconomic status. In addition to supplementing our current understanding of Teotihuacan foodways and processes of geographic migration into the city, I identify an adult male individual from the La Ventilla B apartment compound who displays dietary changes throughout his life that are consistent with downward socioeconomic mobility from a high status socioeconomic group in early adolescence to an intermediate status group later in adulthood. I conclude by identifying ways to move forward with the comparative archaeology of socioeconomic mobility in premodern contexts and highlight the applicability of archaeological information to our understanding of present-day processes of social mobility.Dissertation/ThesisDoctoral Dissertation Anthropology 201

Annual Report 2016 Institute of Resource Ecology

The Institute of Resource Ecology (IRE) is one of the eight institutes of the Helmholtz-Zentrum Dresden – Rossendorf (HZDR). The research activities are mainly integrated into the program “Nuclear Waste Management, Safety and Radiation Research (NUSAFE)” of the Helmholtz Association (HGF) and focused on the topics “Safety of Nuclear Waste Disposal” and “Safety Research for Nuclear Reactors”..

Developing a workflow for the multi-omics analysis of Daphnia

In the era of multi-omics, making reasonable statistical inferences through data integration is challenged by data heterogeneity, dimensionality constraints, and data harmonization. The biological system is presumed to function as a network where the physical relationships between genes (nodes) are represented by links (edges) connecting genes that interact. This thesis aims to develop a new and efficient workflow to analyse non-model organism multi-omics data for researchers who are entangled in the biology questions by using readily available software tools. The proposed approach was applied to the transcriptome and metabolome data of Daphnia magna under various dose rates of gamma radiation. The first part of this workflow compares and contrasts the transcriptional regulation of short-and long-term gamma radiation exposure. A group of genes which share a similar expression across different samples under the same conditions are known as modules, because they are likely to be functionally relevant. Modules were identified using WGCNA but biologically meaningful modules (significant modules) were selected through a novel approach that associates genes with significantly altered expression levels as a result of radiation (i.e. differentially expressed genes) with these candidate modules. Dynamic transcriptional regulation was modelled using transcription factor (TF) DNA binding patterns to associate TFs with expression responses captured by the modules. The biological functions of significant modules and their TF regulators were verified with functional annotations and mapped into the proposed Adverse Outcome Pathways (AOP) of D. magna, which describes the key events which contribute to fecundity reduction. The findings demonstrate that short term radiation impacts are entirely different from long term and cannot be used for long term prediction. The second part investigates the coordination of gene expression and metabolites with differential abundances induced by different gamma dose rates and the underlying mechanisms contributing to the varying extent of the reduction in fecundity. Significant modules which belong to the same design model of dose rates were combined and annotated with new functionality. The abundance of metabolites was also modelled with the same design model. Integrated pathway enrichment analysis was performed to discover and create pathway diagrams for visualising the multi-omics output. Finally, the performance of this workflow on explaining the reduction of fecundity of D. magna, which has not been described in previous studies, has been evaluated. Combining the information from the metabolome and transcriptome data, new insights suggest that the alteration to the cell cycle is the underlying mechanism contributing to the varying reduction of fecundity under the effect of different dose rates of radiation.M-G

Patterns and Signals of Biology: An Emphasis On The Role of Post Translational Modifications in Proteomes for Function and Evolutionary Progression

After synthesis, a protein is still immature until it has been customized for a specific task. Post-translational modifications (PTMs) are steps in biosynthesis to perform this customization of protein for unique functionalities. PTMs are also important to protein survival because they rapidly enable protein adaptation to environmental stress factors by conformation change. The overarching contribution of this thesis is the construction of a computational profiling framework for the study of biological signals stemming from PTMs associated with stressed proteins. In particular, this work has been developed to predict and detect the biological mechanisms involved in types of stress response with PTMs in mitochondrial (Mt) and non-Mt protein. Before any mechanism can be studied, there must first be some evidence of its existence. This evidence takes the form of signals such as biases of biological actors and types of protein interaction. Our framework has been developed to locate these signals, distilled from “Big Data” resources such as public databases and the the entire PubMed literature corpus. We apply this framework to study the signals to learn about protein stress responses involving PTMs, modification sites (MSs). We developed of this framework, and its approach to analysis, according to three main facets: (1) by statistical evaluation to determine patterns of signal dominance throughout large volumes of data, (2) by signal location to track down the regions where the mechanisms must be found according to the types and numbers of associated actors at relevant regions in protein, and (3) by text mining to determine how these signals have been previously investigated by researchers. The results gained from our framework enable us to uncover the PTM actors, MSs and protein domains which are the major components of particular stress response mechanisms and may play roles in protein malfunction and disease

On the genus Crossaster (Echinodermata, Asteroidea) and its distribution

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