Welcome to the eilslabs

The eilslabs form a joint research group between the division "Theoretical Bioinformatics" at the German Cancer Research Center (dkfz) and the department Bioinformatics and Functional Genomics at the Institute of Pharmacy and Molecular Biotechnology (IPMB) at Heidelberg University. The group is headed by Prof. Roland Eils.

 


Our recent article on epigenetic impact of smoking has been featured in Science:

MSB vol12 03 cover RGB RE IL 2 red 400pxZahn, L. M. (2016). Getting more than Mom's looks. Science, 352(6284), 425-426. doi:10.1126/science.352.6284.425-d

 

 

The German Research Summit (Forschungsgipfel 2016) brings together top-ranking representatives from industy, politics and research. Topic of the 2016 edition on April 12 was "digitalization" as the main topic of our time influencing all areas of modern life. The event was jointly organized by the "Stifterverband für die Deutsche Wissenschaft", the German National Academy of Sciences Leopoldina and EFI, the expert commission for research and innovation of the German government.
During the summit, experts from industry, science and representatives of the civil society jointly discussed challenges and opportunities of the digital area for research in Germany. Most prominent participant was the German chancellor Angela Merkel.

Roland Eils, head of eilslabs, was invited to join the first discussion round featuring high-ranking officials such as Angela Merkel, Dieter Zetsche (CEO Daimler), Timotheus Höttges (CEO Deutsche Telekom),  Jörg Hacker (Leopoldina) and Andreas Barner (CEO Boehringer Ingelheim). The proponents in the round discussed the broad implications which the digital revolution has on many aspects of modern life including amongst other autonomous driving, data security and digital health.

More on the Research Summit:

Forschungsgipfel-2016 600px

First row: Dietmar Harhoff (Spokesperson EFI), Timotheus Höttges (CEO Deutsche Telekom), Dirk Ahlborn (CEO Jumpstart), Chancellor Angela Merkel, Andreas Barner (Deutscher Stifterverband and CEO of Böhringer Ingelheim), Roland Eils
Picture by: David Ausserhofer, http://www.forschungsgipfel.de/fotos/index.html

 

New joint study of the eilslabs and the UFZ in Leipzig decrypts the epigenetic impact of smoking on the gene regulatory machinery

Numerous epidemiological studies have demonstrated that maternal smoking has a strong negative impact on the health of newborn child, for example laying the ground for later allergic affections. However, the molecular mechanisms involved remained so far obscure. Several members of the eilslabs under the lead of Roland Eils and Carl Herrmann have now published a study in Molecular Systems Biology in collaboration with a team from the UFZ Leipzig led by Irina Lehmann. In the study they describe the epigenetic mechanisms that are perturbed by maternal smoking, both in mothers and in children. Thanks to a comprehensive epigenetic dataset (whole genome bisulfite sequencing and ChIP-seq), they were able to show that enhancers, regulating the gene expression of distal genes, appear to be specifically targeted by DNA methylation changes.  These hypo/hyper methylations modulate the activity of these regulatory elements, leading to downstream changes in the expression of genes involved in important developmental pathways such as the Wnt pathway. These results raise the intriguing hypothesis that distal regulatory hubs, rather than gene promoters, are prone to be perturbed by environmental cues, explaining their widespread downstream effects.

Maternal Smoking is Harmful!

Cover Image of Molecular Systems Biology featuring the study: Smoking during pregnancy causes epigenetic reprogramming in mothers and children. © Molecular Systems Biology, EMBOpress



Publication:

  • Bauer T, Trump S, Ishaque N, Thürmann L, Gu L, Bauer M, Bieg M, Gu Z, Weichenhan D, Mallm J, Röder S, Herberth G, Takada E, Mücke O, Winter M, Junge KM, Grützmann K, Rolle-Kampczyk U, Wang Q, Lawerenz C, Borte M, Polte T, Schlesner M, Schanne M, Wiemann S, Geörg C, Stunnenberg HG, Plass C, Rippe K, Mizuguchi J, Herrmann C, Eils R, Lehmann I (2016). Environment-induced epigenetic reprogramming in genomic regulatory elements in smoking mothers and their children. Molecular Systems Biology http://dx.doi.org/10.15252/msb.20156520

This research was supported by the DKFZ’s Heidelberg Center for Personalized Oncology (DKFZ-HIPO).

Press Coverage:

Further information:

Dr. Irina Lehmann
UFZ Department of Environmental Immunology
Department of Environmental Immunology
This email address is being protected from spambots. You need JavaScript enabled to view it.
and
Prof. Dr. Roland Eils
German Cancer Research Center and the University of Heidelberg
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CNAG sequenceRecently, researchers from the eilslabs have published together with colleagues from the DKFZ, the CNAG-CRG (Centro Nacional de Analisis Genómico) in Barcelona and the International Cancer Genome Consortium (ICGC) a benchmarking study in Nature Communications to evaluate experimental methods and bioinformatic analyses of next generation sequencing studies in the context of cancer genomics.
As a result of the study, the group, which was led by Ivo Gut from the CNAG-CRG, David Jones from the DKFZ and Roland Eils published a sequencing data record to serve as a “gold standard” for sequence analysis alongside with guidelines for bioinformatic evaluation. Laboratories that start out in the field of genome analysis can now use this data record as a basis to check whether the bioinformatic methods that they are using are capable of detecting all mutations concealed therein. This hopefully helps the international cancer genomics community to establish desperately needed standards for bioinformatics analysis.

Within the eilslabs, the study was driven forward by PhD student Ivo Buchhalter from the Computational Oncology group.

Further Information:

  • Publication:
    Alioto, T.S.*, Buchhalter, I.*, Derdak, S., Hutter, B., Eldridge, M.D., Hovig, E., Heisler, L.E., Beck, T.A., Simpson, J.T., Tonon, L., Sertier, A.S., Patch, A.M., Jager, N., Ginsbach, P., Drews, R., Paramasivam, N., Kabbe, R., Chotewutmontri, S., Diessl, N., Previti, C., Schmidt, S., Brors, B., Feuerbach, L., Heinold, M., Grobner, S., Korshunov, A., Tarpey, P.S., Butler, A.P., Hinton, J., Jones, D., Menzies, A., Raine, K., Shepherd, R., Stebbings, L., Teague, J.W., Ribeca, P., Giner, F.C., Beltran, S., Raineri, E., Dabad, M., Heath, S.C., Gut, M., Denroche, R.E., Harding, N.J., Yamaguchi, T.N., Fujimoto, A., Nakagawa, H., Quesada, V., Valdes-Mas, R., Nakken, S., Vodak, D., Bower, L., Lynch, A.G., Anderson, C.L., Waddell, N., Pearson, J.V., Grimmond, S.M., Peto, M., Spellman, P., He, M., Kandoth, C., Lee, S., Zhang, J., Letourneau, L., Ma, S., Seth, S., Torrents, D., Xi, L., Wheeler, D.A., Lopez-Otin, C., Campo, E., Campbell, P.J., Boutros, P.C., Puente, X.S., Gerhard, D.S., Pfister, S.M., McPherson, J.D., Hudson, T.J., Schlesner, M., Lichter, P., Eils, R.@, Jones, D.T. @, & Gut, I.G. @ (2015). A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing. Nature Communications, 6, 10001. doi: 10.1038/ncomms10001
    @: Joint Supervision; *: equal contribution
  • DKFZ Press Release
  • CNAG Press Release

Since Monday, international researchers are meeting at the DKFZ to present the latest research results during the Systems Biology of Human Disease - SBHD conference organized by the eilslabs. Overarching topic of the conference is the use of mathematical methods and computer models to capture and study complex biological systems. Using this type of systems biology approaches, it is possible to recognize hidden relationships that are important for the emergence of complex diseases such as cancer.DSC 0522 600px

The SBHD conference series was initiated by Peter Sorger from Harvard Medical School in Boston a few years ago and has since developed into a German-American which is held alternately in Boston and Heidelberg.

On Wednesday, the last day of the conference program, two awards will be presented:

  •   Karsten Rippe (DKFZ Heidelberg and BioQuant) will receive the CSB2 Price in Systems Biology (kindly sponsored by Merrimack Pharmaceuticals) for his interdisciplinary work on the structural organization of our genome and its influence on gene regulation and disease development.
  • Kazuki Tainaka from Tokyo University will be awarded the Anne Heidenthal Prize for Fluorescence Research (kindly sponsored by Chroma Technology Corp.), for the development of CUBIC method (Clear, Unobstructed Brain Imaging cocktails and Computational Analysis). The CUBIC method is a newly developed imaging method using a combination of chemical discoloration and light-sheet fluorescent microscopy to achieve extremely detailed pictures of the inside of individual organs and even entire organisms.

Further Information:

ausgabe09Recently the ninth issue of systembiologie.de has been released. The magazine is produced by the eilslabs together with German systems biology initiatives.
Topics of this issue include interviews with renowned systems biologists Gene Myers and Alexander Hoffmann, new insights into wound healing and optogenetics alongside many other interesting articles.
The electronic version can be downloaded here. The International Edition in English will be issued soon.

 

Malte Wachsmuth (EMBL) and Christian Conrad (eilslabs) recently described in Nature Biotechnology an automated systematic approach to measure fluorescence correlation spectroscopy (FCS) in living cells. They unattendly acquired more than 60,000 FCS measurements in more than 10,000 cells, which then were analyzed automatically using specialized software tools developed at DKFZ by Christian Conrad. Systems biology applications of this work  are e.g. live cell proteomics and the mapping of protein behavior within cells.

Further Information:

  • Wachsmuth, M., Conrad, C., Bulkescher, J., Koch, B., Mahen, R., Isokane, M., Pepperkok, R., & Ellenberg, J. (2015). High-throughput fluorescence correlation spectroscopy enables analysis of proteome dynamics in living cells. Nat Biotechnol. doi: 10.1038/nbt.3146
  • EMBL Press Release

Conrad FCS 2015 450px

Automatic high-throughput FCS enables systematic approches to model protein complexes using kinetic parameters in vivo.


The special issue on synthetic biology features many contributions from the international symposium “Synthetic Biology – from understanding to application”, which was hosted by the Helmholtz Initiative on Synthetic Biology at DKFZ in 2013. In their editorial “synthetic biology – ready for application”, the guest editors Roland Eils, Wolfgang Wiechert and Julia Ritzerfeld emphasize that there is already a lot of “synthetic biology inside” many biotechnology-oriented applications. Examples highlighted in this issue include streamlining the genomes of chassis organisms or constructing novel synthesis pathways. Further articles show the establishment of innovative genetic and molecular tools in microbial and mammalian synthetic biology. Three reviews summarize advances in mammalian optogenetics and synthetic viral delivery systems for genome editing, as well as recent advances in RNA aptamer development.

 


A recent publication by eilslabs postdoc Tobias Ahsendorf (1) is the subject of a commentary in BMC Biology by David Pincus (Whitehead Institute, 2). The comment highlights the fact that although life is an excursion away from equilibrium, common models of gene regulation are based on the assumption that it is an equilibrium process. In our paper, which was developed in collaboration between the eilslabs and Jeremy Gunawardena’s lab from Harvard Medical School, we propose a graph-based framework for modeling gene regulation that can accommodate non-equilibrium mechanisms.

Figure 3 Ahsendorf et al

From: Ahsendorf et al.BMC Biology 2014 12:102   doi:10.1186/s12915-014-0102-4

  1. Ahsendorf, T., Wong, F., Eils, R., & Gunawardena, J. (2014). A framework for modelling gene regulation which accommodates non-equilibrium mechanisms. BMC Biology, 12. doi: 10.1186/s12915-014-0102-4
  2. Pincus, D. (2015). Keeping up with the 'omics: non-equilibrium models of gene regulation. BMC Biology, 13(9). doi: 10.1186/s12915-015-0117-5

In a recent interview in the Frankfurter Allgemeine Sonntagszeitung, Roland Eils and Christof von Kalle (NCT) stress the importance of genome sequencing approaches for cancer diagnosis and targeted therapy. Von Kalle sees a “fascinating potential to access all available information on the disease of our cancer patients to help making more intelligent decisions at the bedside”. A prominent example of how the analysis of cancer genomes will influence cancer therapy is the discovery that pilocytic astrocytoma is a single pathway disease, recently published by the Lichter and Eils group at DKFZ (see below and Jones, Hutter, Jäger et al., Nature Genetics 2013). Moreover, “since three years, many lung cancer patients are stratified according to a genetic diagnosis, which identifies cancer subtypes and determines their therapy” says von Kalle. During the interview, Roland Eils emphasizes the constant need of new investments in IT infrastructure and personnel for handling and analysis of large amounts of data: “companies like Twitter have a hundred times more personnel to handle their data flow, though data volumes are comparable”. The interview is available online (in German only).

 

Pilocytic Astrocytoma - identified as a single pathway disease through whole genome sequencing

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For further information please see the news feature: Pilocytic astrocytoma is predominantly a single-pathway disease

Source: Reprinted by permission from Macmillan Publishers Ltd: Jones, D. T. W., Hutter, B., Jager, N., et al. (2013). Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma. Nature Genetics, doi: 10.1038/ng.2682

 

The new publication, which has been produced in collaboration between the eilslabs and labs of Christoph Plass (DKFZ) and Raffaella Santoro (University of Zurich), describes that BAZ2A is an epigenetic regulator, which is overexpressed in malignant prostate cancer and it is involved in the epigenetic silencing of genes repressed during metastasis. The published work was part of the PhD thesis of Lei Gu, who shares first authorship with Sandra Frommel from Zurich, Christopher C. Oakes from the Plass lab and Ronald Simon from the group of Guido Sauter. The results are part of the ICGC project on early-onset prostate cancer.

Figure5 Gu et al NG 2014 small

A heat map of the DNA methylation values of the 3,000 most variable CpG sites from 450K array analysis, shows, that epigenetic remodeling occurs in prostate tumors overexpressing BAZ2A.

Source: Adapted by permission from Macmillan Publishers Ltd: Gu et al. (2014) Nature Genetics doi: 10.1038/ng.3165

Further Reading:

  • Publication: Gu, L.*, Frommel, S.C.*, Oakes, C.C.*, Simon, R.*, Grupp, K., Gerig, C.Y., Bar, D., Robinson, M.D., Baer, C., Weiss, M., Gu, Z., Schapira, M., Kuner, R., Sultmann, H., Provenzano, M., Cancer, I.P.o.E.O.P., Yaspo, M.-L., Brors, B., Korbel, J., Schlomm, T., Sauter@, G., Eils, R.@, Plass, C.@, & Santoro, R.@ (2014). BAZ2A (TIP5) is involved in epigenetic alterations in prostate cancer and its overexpression predicts disease recurrence. Nature Genetics, 47,  22–30 (2015). doi: 10.1038/ng.3165
  • DKFZ Press Release
  • News on a previous publication from the ICGC EOPC consortium

 

Roland Eils The HMLS Investigator Award, which is presented by the Heidelberg Molecular Life Sciences (HMLS) initiative, honors the scientific achievements and their special commitment to the Heidelberg life sciences of the awardees. The 2014 prize, which is endowed with € 100,000, is shared between Roland Eils and Hellmut Augustin and will be officially presented on Friday, December 5, at 5pm in the Greenier-Saal in BioQuant.

 

 

Stefan Kallenberger, Postdoc in the Theoretical Systems Biology group of the eilslabs, hasrecently received the second price at the Roche Oncology Award for his work on dose-dependent induction of apoptosis. The figure below gives a brief insight into his work. The prize was handed over by Klaus Bosslet, Roche’s head of Discovery Oncology in Penzberg on November 19.

Congratulations to Stefan!

cell ensemble modell Kallenberger 500px A cell ensemble model can be used to predict dose adapted optimal injection rates for a death receptor agent. After having calibrated a biochemical signal transduction model with experimental data, and having estimated parameters of the multivariate distribution of initial signaling species concentrations and tBID thresholds, surviving fractions of cells can be predicted that result from death receptor agent trajectories. It can be demonstrated, that based on a signal transduction model, dependent on pharmacodynamic parameters, optimal injection rates for a given dose of death receptor agent can be predicted. With increasing dose (D) of a death receptor agent, the optimal injection rate (arrows) increases. Source: Stefan Kallenberger

 

 

doktorandenpreis

The Helmholtz PhD Award is assigned to six young scientists for their accomplishments in key areas of modern science (Energy, Earth and Environment, Health, Aerospace and Transportation, Key Technologies, Structure of Matter). With this award, the Helmholtz-Society wants to encourage talented scientists to continue pursuing their research interests in the long term. The prize is endowed with 5.000 EUR and an allowance of 2.000 EUR per month “scholarship” to conduct research in an international institution for up to six months. The prize was awarded by the Federal Minister for Education and Research, Dr. Johanna Wanka, during a ceremony on September 18 in Berlin.

Natalie Jäger, former PhD student in the eilslabs, was awarded in the category Health, based on her outstanding achievements in uncovering genetic alterations in medullablastoma and astrocytoma, the most common malignant brain tumours in children. Throughout her PhD she was an important figure in the DKFZ-Project “PedBrain Tumour”, which is funded by the BMBF and the German Cancer Aid to shed light on the genetic causes of paediatric brain tumours. Her findings are of great importance for the development of new therapeutics against specific types and subtypes of brain cancer.

Jäger earned her doctorate on the thesis “Computational analysis of cancer genome sequencing data – the genetic landscape of paediatric brain tumours and X chromosome hypermutation” in 2014. She now works as a Postdoc in the lab of Michael Snyder at Stanford University in Berkeley, USA.