Previous lectures (2013-)
Date: Monday, December 8th, 10:30am, KUBUS Hall1A
Presenter: Kathrin Fenner (EAWAG)
Title: “Towards a more accurate prediction of the biotransformation of chemical contaminants – What we can learn from combining data mining, analytical chemistry and molecular biology tools”
Host: Prof. Dr. Hauke Harms
Date: Wednesday, December 3rd, 01:00pm, KUBUS Hall1CD
Presenter: Katrin Wendt-Potthoff (SEEFO)
Title: “The plastisphere – microplastics in aquatic ecosystems”
Host: Dr. Lukas Wick & Prof. Dr. Rolf Altenburger
Plastic debris in the oceans is a well-known and publicly discussed environmental problem. However, despite the fact that up to 80% of marine plastic pollution originates in the terrestrial environment, transport and ecosystem effects of plastics in limnic systems are not well studied. The presentation introduces the challenges of microplastic quantification in the environment, summarizes present knowledge on plastics in rivers and lakes, and highlights approaches to study colonization and degradation of microplastics by microbes. Based on this, knowledge gaps and research needs can be discussed.
Date: Tuesday, December 2nd, 02:00pm, KUBUS Hall1A
Presenter: Kristopher McNeill (ETH Zürich)
Title: “Environmental Photochemistry: From Triclosan to Dioxins”
Host: Prof. Dr. Thorsten Reemtsma
Abstract:Triclosan is an antibacterial compound widely used in consumer products, including liquid soaps and toothpaste. Accordingly, triclosan has been found in surface waters that receive wastewater all over the world. Prior work has identified photochemical degradation as a major loss process for triclosan in surface waters, which leads to short persistence of triclosan in such systems. This seemingly happy circumstance is accompanied by the worrisome discovery that triclosan’s transformation products include chlorinated phenol, chlorinated dioxin and dihydroxy-PCB products. More recent work has revealed that the water treatment strategies greatly influence the prevalence of more toxic dioxin congeners in environmental systems. This presentation will summarize the current state of knowledge and present unpublished work on the photochemistry of triclosan.
Date: Wednesday, November 26th 03:00pm, building 1.0 lecture hall
Presenter: David Werner (Newcastle University)
Title: “Sorption and Biodegradation: A complicated relationship”
Host: Dr. Lukas Wick & Dr. Beate Escher
Abstract:Sorption and biodegradation are fundamental processes contributing to the attenuation of organic pollutants in soils and sediments. While sorption reduces the mobility and often also toxicity of organic pollutants, it can hinder the pollutant biodegradation and enhance persistence. Many laboratory studies have demonstrated that sorption reduces the bioavailability of pollutants and hence the pollutant transformation by microorganisms. This presentation, however, will argue that the persistence of organic pollutants in the natural environment is often due to biological limitations in which case sorption can help with the pollutant biodegradation along a source-receptor pathway. Furthermore, extracellular electron transfer through the matrix of carbonaceous sorbents with high aromaticity ("black carbon") will be discussed as an interesting new mechanism by which sorption may assist with the dechlorination of persistent pollutants like DDT in anaerobic soils and sediments. Consideration of such mechanisms is of great importance for the design and monitoring of in-situ soil and sediment remediation strategies which use strong sorbents like activated carbon or biochar.
Date: Wednesday, November 26th 12:30pm, building 6.0 room 111
Presenter: Xiaowei Zhang, PhD (Nanjing University, China)
Title: “Development of Next Generation Technologies for Environmental Monitoring and Ecological Risk Assessment”
Host: Dr. Werner Brack
Abstract:Prof Zhang's research interests include ecotoxicology of environment pollutants and chemical safety research. The current research focuses on mechanistic toxicology of emerging chemicals and environmental genomics, in particular, the development of Next Generation Sequence (NGS) technology based high throughput assays for chemical toxicity assessment and ecological monitoring of biodiversity. His research involves both laboratory experiments and field studies (e.g. biomonitoring using environmental DNA)
Date: Tuesday, November 25th, 03:00pm, building 6.0 room 111
Presenter: Dr. April Gu (Northeastern University Boston)
Host: Prof. Dr. Beate Escher
Title: "Explore Quantitative Toxicogenomics For Toxicity Assessment and Water Quality Monitoring"
Abstract: The contaminants of emerging concern (CECs), such as endocrine disrupting compounds (EDCs), pharmaceuticals, personal care products (PPCPs) and nanomaterials, are anticipated to greatly increase the demands for their toxicity, ecological effects and risk assessments. Current whole animal/organism exposures-based methods used for regulatory decision-making in ecotoxicology are resource and time-intensive and, they provide little information on toxicity mode of action (MOA) and cellular level sub-lethal impact. Alternative and/or complimentary toxicity screening methods, which are less costly, yet with informative endpoints are needed. Recently, we have explored the application of a toxicogenomics approach for toxicity assessment and screening of CECs, using a comprehensive GFP-infused bioluminescent whole cell array. Compared with traditionally microarray technology, this method is simpler and faster, and therefore is feasible for screening a large number of chemicals. Furthermore, it provides multi-dimensional transcriptional level effect information, by adding a temporal dimension to the gene expression data, and therefore can more accurately reflect the chemical-induced cell responses that are time-dependent. We demonstrated that toxicogenomic data could also be used to potentially identify and classify compounds with similar MOAs (mode of action) while gaining diagnostic insights into the causal agents. One of the main challenges in applying toxicogenomics for environmental monitoring is the lack of a quantitative method to convert the rich toxicogenomic information into a readily usable and transferable format that can potentially link to regulation endpoints and be incorporated into ecological risk assessment and regulatory framework. We proposed a new transcriptional effect level index (TELI) that exhibited a dose-response relationship and allowed for linking (“phenotype anchoring”) the transcriptional level effects to conventional toxicity endpoints. Cross-species comparison and extrapolation is another key aspect related to predictive and mechanistic toxicity assessment to overcome the limitation of data generation ability. We have compared genotoxicity across three different species for variety of compounds and demonstrated the possibility of cross-species extrapolation with stress-response pathway ensemble based toxicity assessment.
Short Bio: Dr. Gu is an associate professor in Civil and Environmental Engineering Department, faculty and track leader for Interdisciplinary Bioengineering Program within the College of Engineering and affiliated faculty for Biotechnology Program with Bouve College of Health Sciences at Northeastern University in Boston. She obtained her B.S. in Environmental Engineering and Science from Tsinghua University in Beijing, China and a Ph.D. in Civil and Environmental Engineering, jointly in Microbiology, from the University of Washington in Seattle. Her expertise and area of research interest include application of biotechnology for water and wastewater treatment, water quality monitoring and toxicity assessment, biosensors, biological wastewater treatment processes and modeling, microbial ecology, bioavailability of nutrients in aquatic systems and bioremediation. She is an Editorial Board member for Water Environmental Research Journal, Frontiers of Toxicogenomics, and Associate Editor for Water Science And Technology Journal. She serves on a number of international and national committees for IWA, WEF and AWWA. She has received a number of national awards including NSF CAREER award in 2009, SETAC Global Best Student Paper Award, ACS Outstanding Presentation Merit Award and Søren Buus Outstanding Research Award from Northeastern University. She was invited speaker for Gordon Conference-Environmental Nanotechnology 2013, and Gordon Conference – Water Science in 2012.
Date: Tuesday, November 25th, 02:00pm, building 6.0 room 111
Presenter: Frank Wania (University of Toronto)
Title: “Simulating differences in exposure to PCBs between generations, sub-populations, and individuals”
Host: Dr. Kai-Uwe Goss
By integrating models of environmental fate and food chain bioaccumulation we now have the capability to mechanistically describe a PCB’s journey from initial release into the physical environment to its accumulation in top predators, including humans. A particularly important feature of the combined model is its dynamic nature, which allows for time-variant simulations covering periods of multiple decades. The integrated model can be used to further our understanding of differences in PCBs exposure between different human generations, between human sub-populations that differ in terms of diet and living environment, or between different wildlife species. The model can also be used to assess the effectiveness of policy options, e.g. the issuing of dietary advisories to reduce infant exposure to PCBs. By combining the model with human biomonitoring efforts, such as NHANES, we currently seek to simulate PCB exposure of individuals. Information on age, year of birth, gender, diet, reproductive behavior (number of children, age at birth, breastfeeding habits), and body mass index obtained through the questionnaires accompanying biomonitoring studies is translated into individualized model input parameters, allowing for a prediction of each study participant’s longitudinal PCB exposure. This not only allows for the identification and quantification of the factors that contribute to the differences in human exposure to PCBs, but could also open the door to predicting exposure during time periods of particular exposure sensitivity earlier in life.
Date: Thursday, November 20th, 10:30am, building 6.0 room 111
Presenter: Samuel Arey (EPFL Lausanne)
Title: “Analysing reactive molecules in aquatic systems using quantum chemistry”
Host: Dr. Kai-Uwe Goss
Aqueous reactive molecules are important agents of chemical transformation in both natural and engineered water systems. However these species are often challenging to study by experiment. Computational quantum chemistry models allow us to explore their structures, properties, energies, and reactivities. In this talk I will discuss results from several in silico studies on aqueous reactive molecules. Focus will be placed on recent efforts to describe chemical equilibria, transformation mechanisms, and one-electron oxidation processes of environmentally relevant aquatic species, using high quality quantum chemistry protocols.
Date: Wednesday, November 12th, 03:00pm, building 1.0 lecture hall
Presenter: Dirk Wagner (GFZ Potsdam)
Title: "What can we learn from the past? - DNA-base reconstruction of the Arctic methane cycle and new insights into the deep biosphere"
Host: Prof. Dr. Matthias Kästner
The currently observed climate change due to global warming is expected to have a strong impact, notably on Arctic permafrost environments. The thawing of permafrost is suggested to be associated with a massive release of greenhouse gases, in particular methane. Thus, Arctic permafrost regions play a fundamental role within the global carbon cycle and the future development of Earth’s climate. To understand how the system will respond to climate changes it is not only important to investigate the current status of carbon turnover but also how the system reacted to climate changes in the past. For this purpose microbiological, molecular ecological and geochemical methods have been applied to analyze permafrost deposits and arctic lake sediments with an age of up to 3.2 million years. This includes the investigation of small‐scale variations within the deep biosphere microbial community structure and their potential metabolic activity along the sediment chronosequences. For DNA‐based community analyses of sediments encompassing geological time scales, an issue from a paramount importance is whether the extracted DNA originates from the modern community or might be an artifact of ancient communities or excreted DNA. We therefore have developed a new procedure for separate recovery of extra‐ and intracellular DNA from a sediment samples (Alawi et al., 2014, J Microbiol Methods 104, 36‐42). This presentation takes a journey through time from the recent active layer of permafrost to Holocene and Late Pleistocene permafrost deposits and older lake sediments in the Siberian Arctic, to describe the microbial driven methane dynamics during glacial‐interglacial climate changes and to give first insights into the ancient and modern bacterial communities in million years old lake sediments.
Date: Tuesday, September 23rd, 02:00pm, building 6.0 room 111
Presenter: Dr. Reinhard Länge (Bayer HealthCare, Bayer Pharma AG)
Title: A strategy to pharmaceuticals in the environment: An industry approach
Host: Dr. Nils Klüver
Date: Thursday, September 11th, 01:00pm, KUBUS Saal 1CD
Presenter: Prof. Dr. A. Alia Matysik (University Leipzig)
Title: Novel magnetic resonance approaches for live zebrafish imaging and metabolic profiling
Abstract: Zebrafish (Danio rerio) has emerged as one of the most promising and cost-effective model systems for environmental toxicity studies as well a powerful model organism for studying vertebrate biology and human diseases. However, in vivo studies in zebrafish are restricted to very early developmental stages due to opaqueness of the juvenile and the adult stages that cannot be approached by optical imaging methods. In this talk, I will present our novel in vivo magnetic resonance microimaging studies to image live adult zebrafish at ultra high magnetic field to get sufficient anatomical details from various parts of adult zebrafish. Furthermore, we have optimized high resolution localized in vivo NMR technique to get access to the metabolic profile of the zebrafish brain in vivo. Methods has been successfully applied to zebrafish models of various human diseases. In addition, prospects of high resolution magic angle spinning NMR approach to study influence of toxic compound on the metabolic profile in intact zebrafish embryos will be discussed.
Host: Stephan Brox
Date: 22.5.2014 (Thu), 3 p.m.
Presenter: Dr. Daniel Stalter
National Research Centre for Environmental Toxicology (Entox) at the University of Queensland in Australia.
Title: Disinfection by-products in drinking water – catching the polar, the volatiles and the unknowns for a comprehensive bioanalytical water quality assessment
Abstract: While drinking water disinfection is one of the major public health advances in the last century, one downside is that the disinfectants also react with organic and inorganic precursors to form potentially hazardous disinfection by-products (DBPs). After 35 years of research the major fraction of formed DBPs are not yet identified and hence, the bioanalytical evaluation of drinking water toxicity is a crucial complement to chemical analysis to evaluate drinking water quality. However, the high enrichment factors commonly required for bioanalytical assessment entail the loss of a significant fraction of volatile and polar DBPs. Here we explored different enrichment methods with the aim to minimise the loss of DBPs. For the toxicological characterisation of the volatile fraction of total DBPs we adapted bioassays to minimise the loss of volatile DBPs during dosing and exposure to the samples. Finally, we evaluated drinking water samples using chemical analysis and bioassays. All detected DBPs have been toxicologically characterised as single compounds and in the mixtures in ratios found in the water samples to evaluate the toxicological relevance of the known DBPs compared to the unknown fraction.
Biosketch: Daniel Stalter studied biology at the Goethe University in Frankfurt. One of his research interests is in the ecotoxicological effect assessment of wastewater. Daniel’s current post-doctoral research at the National Research Centre for Environmental Toxicology (Entox) at the University of Queensland (Australia) focuses on drinking water treatment and the bioanalytical toxicity assessment of disinfection by-products (DBPs).
Host: Beate Escher (Zelltox)
Date: 20.5.2014 (Tue), 3 p.m., Building 6, Room 111
Presenter: Dr. Peta Neale
National Research Centre for Environmental Toxicology (Entox) at the University of Queensland in Australia.
Title: Toxic tattoos? Bioanalytical evidence that tattoo ink can induce oxidative stress and genotoxicity
Abstract: Tattooing has become increasingly popular, particularly among young people. Previous studies have shown that tattoo inks can contain hazardous chemicals, such as polycyclic aromatic hydrocarbons (PAHs), but little is known about the potential health risks posed by tattoo inks. In this seminar I will present our recent work on using cell-based bioanalytical tools to assess the toxicological hazard of tattoo inks. Bioanalytical tools relevant to human health including oxidative stress and genotoxicity were applied to a range of tattoo ink extracts. Chemical analysis was utilized to determine how much of the observed effect could be related to known chemicals. Finally, a tattoo bioanalytical equivalent measure was established, which may be used to compare chemical exposure from tattoos to other sources of exposure.
Biosketch: Peta Neale is an environmental scientist and the central theme of her research is to understand the fate and effect of chemicals. She is a research fellow at the National Research Centre for Environmental Toxicology (Entox) at the University of Queensland in Australia. She has a PhD in Environmental Engineering from the University of Edinburgh, UK.
Host: Beate Escher (ZELLTOX)
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)