Previous lectures (2013-)
10.4.2014 (Thu), 15:30-16:30,
KUBUS, Hall 1A
Knut Erik Tollefsen
Norwegian Institute for Water Research (NIVA),
Adverse Outcome Pathways - providing the linkage between mechanistic studies and regulatory processes?
This talk will discuss the use of the Adverse Outcome Pathway (AOP) concept as a framework to characterize, organize, and define predictive relationships between measurable biological key events following chemical exposure of organisms. In particular it will reflect the progression from a chemical-induced perturbation to an adverse outcome as relevant to regulatory decision-making in ecotoxicology.
Host: Rolf Altenburger (BIOTOX)
9.4.2014 (Wed), 10:00-11:00, KUBUS, Hall 1A
Institute of Integrative Biology
University of Liverpool, UK
Towards predictive ecotoxicology – Understanding and predicting the molecular impact of compound exposure
Systems biology, particularly predictive modelling, is showing great potential for understanding and predicting the underlying molecular response to exposure. Here we use the transcriptional readout of a biosensor, such as Daphnia magna, to develop predictive models of chemical class and identify a novel calcium dependent mechanism for basal toxicity. Lastly, with similar approaches, a proof of concept study will show how such methodologies may also be used for predicting complex mixtures and hence provide a complimentary tool for current regulatory purposes.
Host: Rolf Altenburger (BIOTOX)
9.4.2014 (Wed), 09:00-10:00, KUBUS, Hall 1A
J. Kevin Chipman
School of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
The epigenome, transcriptome and metabolome associated with carcinogenesis in fish from the environment
Carson’s “Silent Spring” approximately 50 years ago raised awareness of the need to protect the environment from chemicals that have the potential to cause ecological and human harm. However the methods for assessing the impact of pollutants on wild organisms in which there is little genomic information has been limited to rather crude, insensitive end points. The rapid expansion of knowledge about gene sequence and function, coupled with “omic” and associated mathematical modeling technologies has provided an unprecedented opportunity to transform environmental monitoring into mechanism-based, sensitive early-warning alerts based on “adverse outcome pathways” that can be prognostic and diagnostic of adverse effects. Transcriptomic analyses, and associated bioinformatic interrogation, can reveal the complex responses to chemicals with potential to cause cancer and other disorders. Models of chemical-induced liver carcinogenesis in zebrafish have revealed remarkable similarities in gene expression and epigenetic marks to those associated wuith human liver cancers. However, although the incidence of liver tumours in fish can reach levels as high at 20% incidence, little is known about the relative importnace of genetic and epigenetic causes. Fish from different environments clearly have different gene expression profiles for many reasons. However, a sub-group of stress-related genes (identified from toxicogenomic studies in fish under laboratory conditions) can be predictive of the pollution exposure in fish taken from different environments in the wild (Williams et. al., PLoS Comput Biol. 2011). Interrogation of gene expression networks can reveal associations between key nodes of the network with health-related parameters. Moreover epigenetic changes, mediated by disturbance of the 1-carbon cycle, can also inform on environmental conditions associated with tumour formation in wild fish. We provide evidence that an epigenetic progenitor cell mechanism may be important in carcinogenesis (Mirbahai et. al. J. Proteome Res., 2013). Thus transciptome and methylome profiles have potential utilisation as complex monitoring biomarkers.
Host: Rolf Altenburger (BIOTOX)
14.03.2014 (Fr), 1 p.m., Building 6, Room 111
Department of Biological Sciences
Graduate Program in Environmental and Molecular Toxicology
North Carolina State University
Physiological approaches to understanding thermal controls on aquatic insect performance
Virtually every aspect of aquatic insect life history is controlled by temperature. Yet, surprisingly little is known about the physiological drivers of thermally mediated life history outcomes. In this talk, I will present the results of several recent laboratory studies that explore the influence of warming on the physiology and life history outcomes of mayflies. A combination of respirometry, qPCR and metabolic profiling work all point towards the importance of temperature controls on bioenergetics. We specifically explored whether oxygen limitation (the mismatch between oxygen supply and demand) could explain ecologically life history outcomes, and found that oxygen limitation only appears relevant during the molt, and during acute thermal challenge (Ct maximum type of experiments), but not ecologically relevant thermal regimes. I will further discuss the respiratory challenge, environmental sensitivity, and costliness of molting.
Host: Matthias Liess (OEKOTOX)
10.03.2014 (Mo), 3 p.m., KUBUS Saal 1 C+D
National Research Centre for Environmental Toxicology (Entox), The University of Queensland, Brisbane, Australia
Processes governing surfactant facilitated transport of superhydrophobic organic compounds
Superhydrophobic organic contaminants (SHOCs) are practically insoluble in water and have a high affinity for organic matter, and therefore are generally considered immobile in soil. Examples include polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated biphenyls and a range of brominated flame retardants and pesticides. Surfactants, however, have the ability to solubilise SHOCs in soil-water and consequently significantly change their mobility in the subsurface. As a result, contaminants may be transported through the soil column, leading to unexpected groundwater contamination. However, surfactant facilitated transport (SFT) processes for SHOCs are still poorly understood and the significance of these transport processes at sites where surfactants and SHOCs are occurring together, such as agricultural sites, is not known. Both these factors need to be understood in order to quantify and if necessary manage, the risks from SFT. If the underlying mechanisms and the parameters that drive these processes are known, then modelling tools can be developed/applied to predict where and to what extent contaminant transport may be occurring in the environment.
The mobility of SHOCs under SFT is largely driven by the partitioning behaviour of these contaminants between water, soil and surfactants. SHOCs can partition to mobile surfactant phases (micelles and monomers) and be transported with soil-water. Conversely, sorption to soil and surfactants sorbed to soil can reduce their mobility. My PhD aims to investigate/quantify the underlying partitioning processes for SFT of SHOCs and apply this knowledge to simulate these processes under conditions relevant to agricultural sites.
Veronika Schacht is PhD student at the University of Queensland, working under the supervision of Dr. Sharon Grant on a Discovery Project funded by the Australian Research Council entitled “Unintentional surfactant facilitated solubilisation and transport of apparently immobile chemicals”, a collaboration between A/Prof. Caroline Gaus and Prof. Beate Escher at the University of Queensland and Dr. Michael Finkel of Tübingen University.
Host: Beate Escher (ZELLTOX)
4.2.2014 (Tue), 2 p.m., KUBUS, Room 1B
Dr. Andrea Bassi
Max Planck Institute of Cell Biology and Genetics, Dresden
Anatomical and functional imaging of zebrafish with Optical Projection Tomography and Selective Plane Illumination Microscopy
Host: Julia Ortmann (BIOTOX)
12.11.2013, 1 p.m., KUBUS, Room 2
Dr. Urs Berger
Department of Applied Environmental Science (ITM), Stockholm University, Sweden
State-of-the-art in trace analysis of per- and polyfluoroalkyl substances
Implications for our understanding of their environmental fate
Twelve years ago, the first scientific reports on the presence of perfluorooctane sulfonic acid (PFOS) in blood serum of the general population and on its global distribution in wildlife were published. This triggered an ever-since increasing number of research studies on per- and polyfluoroalkyl substances (PFASs) in humans and the environment. The majority of these studies are based or rely on chemical analysis of PFASs in a variety of matrices. Many of the early-recognized challenges specific to trace analysis of PFASs have eventually been overcome as well-characterized chemical standards became available and analytical methods evolved. Today, a number of highly sensitive methods are described for quantification of many classes of PFASs in a multitude of matrices. The presentation investigates to what extent these existing methods are able to supply the analytical data needed to understand key issues such as environmental sources, transport and fate or human exposure sources and pathways for different PFASs. Potential shortcomings and quality gaps of commonly applied methods, such as procedural blank contamination, matrix effects and varying response factors of structural isomers, are also discussed. A special focus is on particular challenges with emerging groups of PFASs such as perfluoroalkyl phosphonic acids and polyfluoroalkyl phosphate esters.
Urs Berger is the head of a research group at the Department of Applied Environmental Science (ITM), Stockholm University, Sweden. His main interest is the development of trace analytical methods for emerging organic contaminants in different environmental matrices. Furthermore, he applies tailor-made methods in order to gain an understanding for environmental and ecotoxicological pollutant dynamics. Over the last twelve years, an increasing focus has been on per- and polyfluoroalkyl substances (PFASs). Urs Berger has published 42 scientific papers in the field of analysis as well as environmental and ecotoxicological process studies of PFASs.
Host: Thorsten Reemtsma (ANA)
19.11.2013, 12 a.m., KUBUS, Room 1CD
Max Planck Institute for Developmental Biology, Tübingen
Biophysics of morphogen transport
The fundamental question of developmental biology is how a single cell can develop into a complex mature organism with hundreds of different types of specialized cells. Cellular communication via signaling molecules, also known as morphogens, is of central importance to generate this diversity during development. We combine genetic, biophysical and theoretical approaches to study how extracellular morphogens move in developing embryos and how they pattern tissues. We found that morphogens move by hindered diffusion in the extracellular space of living zebrafish embryos: Locally, morphogens can move freely, but their global movement through embryonic tissues is hindered by cell packing (tortuosity) and transient binding to diffusion regulators. Interestingly, differential diffusivity - not stability - of morphogens underlies tissue patterning, consistent with classic reaction-diffusion models that have been postulated to generate complex self-organizing patterns during development.
Host: Till Luckenbach (BIOTOX)
05.11.2013, 10 a.m., KUBUS, Room 1B
Dr. Sonja Hänzelmann
Computational Biology Group, RTWH Aachen, Germany
Computational methods for the analysis of high-throughput data
The computational biology group focuses on regulatory genomic events such as chromatin remodeling, transcription factor binding site detection, gene expression and influence of non-coding RNA during biological processes as diseases and cell development. In this talk, I will describe two current projects: (1) computational deteciton of long-non coding RNA interactions with the DNA and (2) pathway analyses based on gene expression data. (1) LncRNAs stear key regulatory processes, seem to be involved in regulating gene expression and have been indicated to modify chromatin structure. Further, lncRNAs are able to form triple helices with the DNA. Recent evidence suggests potential regulatory roles of regions where triple helices can be formed. The experimental detection of triple helix forming complexes proves to be difficult, therefore a computational method (Triplexator) was developed. The algorithm efficiently detects triple helix complexes on a genome-wide scale. However, genome-wide search of binding sites leads to a high number of false positive predictions, which are unlikely to be functional in a particular biological context. To address this problem, we developed an extension to the Triplexator method and found that lncRNAs use multiple TFOs to bind to particular sites. Further, DNA-lncRNA interactions might be arising from the combinatorial use of one or more interaction domains of the lncRNA. (2) We developed Gene Set Variation Analysis (GSVA), a method that condenses gene expression profiles into a pathway signature summary over a sample population in an unsupervised manner. GSVA can be applied to microarray and RNA-seq data equally and is available at Bioconductor. We provide examples of its utility in differential pathway activity and survival analysis. We demonstrate the robustness of GSVA in a comparison with current state of the art sample-wise enrichment methods. Further, we provide examples of its utility in differential pathway activity and survival analysis. Lastly, we show how GSVA works analogously with data from both microarray and RNA-seq experiments.
Host: Wibke Busch (Biotox)