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.

 


 

"How do ovarian cancer patient cells grow in 3D culture? Can we use them in personalized drug screens?" With these questions, a collaboration between the eilslabs and Martin Sprick's and Andreas Trumpp's group at HI-STEM and DKFZ started. A newly image-based assay drug was developed and used to systematically compare drug responses between 2D and 3D. In addition in collaboration with CO group, novel links between patient drug responses and genomic aberrations were discovered, altogether laying a foundation for advanced drug screening in personalized oncology and pharmacogenomics.

Thanks to our collaboration partners and all people involved in the eilslabs!

MSB-17-7697RR_synopsis_large.jpg

Citation:

Jabs J, Zickgraf FM, Park J, Wagner S, Jiang X, Jechow K, Kleinheinz K, Toprak UH, Schneider MA, Meister M, Spaich S, Sütterlin M, Schlesner M, Trumpp A, Sprick M, Eils R, Conrad C.: Screening drug effects in patient-derived cancer cells links organoid responses to genome alterations. Molecular Systems Biology 2017 Nov 27;13(11):955. doi: 10.15252/msb.20177697.

 

Together with an international research team, researchers from the eilslabs performed a study to decipher the genomic landscape of aggressive medulloblastoma subtypes. Medulloblastoma is a brain cancer that can occur in adults as well as in children. Of the classified four distinct molecular-biological subgroups, especially the tumors of groups 3 and 4 are very common in children but yet not well studied. This often results in unspecific treatments with severe side effects.


With the analysis of almost 500 medulloblastomas the study unraveled almost 80 percent of the genetic alterations in groups 3 and 4, revealing new cancer genes. Furthermore, the scientists found new candidate drivers for a genetic alteration called "enhancer hijacking". In this process, structural changes in the DNA result in the activation of oncogenes, which should normally be inactive. By changing their position these oncogenes become activated by an enhancer thereby contributing to the development of cancer.
With these new results the medulloblastoma subgroups can be classified more precisely providing the opportunity for specified treatments with a concomitant reduction of side effects.


Within the eilslabs, the study was driven forward by Ivo Buchhalter, former PhD student in the Computational Oncology group, with Roland Eils supervising the study.
This work was supported by the International Cancer Genome Consortium PedBrain Tumour Project, funded by the German Cancer Aid and by the German Federal Ministry of Education and Research.

Pfister Nature MRT Medulloblastom

MRT-Image of a Medulloblastoma  © DKFZ

 

Publication:

  • Paul A. Northcott*, Ivo Buchhalter*, A. Sorana Morrissy*, Volker Hovestadt, Joachim Weischenfeldt, Tobias Ehrenberger, Susanne Groebner, Maia Segura-Wang, Thomas Zichner, Vasilisa Rudneva, Hans-Jörg Warnatz, Nikos Sidiropoulos, Aaron H. Phillips, Steven Schumacher, Kortine Kleinheinz, Sebastian M. Waszak, Serap Erkek, David T.W. Jones, Barbara C. Worst, Marcel Kool, Marc Zapatka, Natalie Jäger, Lukas Chavez, Barbara Hutter, Matthias Bieg, Nagarajan Paramasivam, Michael Heinold, Zuguang Gu, Naveed Ishaque, Christina Jäger-Schmidt, Charles D. Imbusch, Alke Jugold, Daniel Hübschmann, Thomas Risch, Vyacheslav Amstislavskiy, Francisco German Rodriguez Gonzalez, Ursula D. Weber, Stephan Wolf, Giles W. Robinson, Xin Zhou, Gang Wu, David Finkelstein, Yanling Liu, Florence M.G. Cavalli, Betty Luu, Vijay Ramaswamy, Xiaochong Wu, Jan Koster, Marina Ryzhova, Yoon-Jae Cho, Scott L. Pomeroy, Christel Herold-Mende, Martin Schuhmann, Martin Ebinger, Linda M. Liau, Jaume Mora, Roger E. McLendon, Nada Jabado, Toshihiro Kumabe, Eric Chuah, Yussanne Ma, Richard A. Moore, Andrew J. Mungall, Karen L. Mungall, Nina Thiessen, Kane Tse, Tina Wong, Steven J.M. Jones, Olaf Witt, Till Milde, Andreas von Deimling, David Capper, Andrey Korshunov, Marie-Laure Yaspo, Richard Kriwacki, Amar Gajjar, Jinghui Zhang, Rameen Beroukhim, Ernest Fraenkel, Jan O. Korbel, Benedikt Brors, Matthias Schlesner, Roland Eils§, Marco A. Marra§, Stefan M. Pfister§, Michael D. Taylor§ and Peter Lichter§: The whole-genome landscape of medulloblastoma subtypes. Nature 2017. DOI:10.1038/nature22973. §: Joint Supervision; *: equal contribution

Press Coverage:

 

As part of the ‘medical informatics’ funding initiative the BMBF provides financing of €150 Mio. On July 10th, the federal minister for education and research, Johanna Wanka, announced that HiGHmed is one of four German consortia selected for funding. HiGHmed will receive around €30 Mio for the upcoming four years to create integrative data centers to promote data exchange and use for enhanced patient-centred therapies. Efficient multi-site data exchange will help use the ever-growing treasure trove of data – from radiologic imaging data to genomic analyses – for better health and medical care.

This is a great success for the HiGHmed team based in Heidelberg, Göttingen and Hannover. HiGHmed is coordinated by Prof. Roland Eils. Together with its partners, the team will use cutting edge information technologies for distinctive use cases in the fields of oncology, cardiology and infection control. The aim will be to fight pathogen outbreaks in hospitals and to treat cancer and cardiovascular diseases through more effective and individualized treatments.

For more information please refer to:

consortia representatives  

highmed consortium members

Minister Johanna Wanka und Alexander Hörbst with representatives of the four consortia selected for funding during the press conference in Berlin, 10.07.2017. From left to right: Alexander Hörbst (chairmen of the reviewer board), Klaus A. Kuhn (consortium DIFUTURE), Markus Löffler (consortium SMITH), Roland Eils (consortium HiGHmed), Johanna Wanka, Hans-Ulrich Prokosch (consortium MIRACUM) Photo: BMBF/Hans-Joachim Rickel

 

HiGHmed consortium members (from left to right during the hearing of the proposal in Berlin, 06.07.2017): Björn Bergh (Heidelberg University Hospital), Otto Rienhoff (University Medical Center Göttingen), Roland Eils (Heidelberg University Hospital and DKFZ), Ramin Yahyapour (University Medical Center Göttingen), Michael Marschollek (Hannover Medical School).

 

In July this year, the International Conference on Systems Biology of Human Disease (SBHD) will take place for the 10th time. National and international renowned speakers will present their latest research results at the German Cancer Research Center and Heidelberg University.
The conference focuses on mammalian systems biology, particularly on its application to human disease and therapy. With the use of mathematical methods, “omics”-technologies, and computer models this interdisciplinary field of science uncovers complex interactions within biological systems such as cancer that can ultimately be applied to translational medicine.

SBHD 2017 is continuing a successful conference series launched in 2008 by Peter Sorger at Harvard Medical School and has developed into a transatlantic event and communication platform for scientific exchange between the United States and Germany. The conference is chaired by Roland Eils and Peter Sorger and organized by the eilslabs.
We are looking forward to exchange new ideas and information with colleagues and peers from around the world and to contribute to a cutting edge scientific program on systems biology.
For registration, abstract submission and more information, please visit the conference website: www.sbhd-conference.org

 

SBHD 2015 2

 

 

systembiologieOur eleventh issue of systembiologie.de has been released. The magazine is produced by the eilslabs together with German Systems Biology Initiatives. In this issue we address Germany’s Science Year 2016*17 – Seas and Oceans with interesting articles from marine systems ecologists from around the world. You will also find new insights into systems biology in the field of plant breeding, ageing research and in the context of animal experiments. Moreover renowned scientists such as gene technology expert Bärbel Friedrich or ageing researcher Karl Lenhard Rudolph talk about their research, ideas and opinion on systems biology in interviews.

The electronic version can be downloaded here. The international edition in English will be issued in June this year.

 

If you are looking for an intersting PhD position at the eilslabs focussing on Cancer Research and beyond, please apply via the DKFZ's Graduate School until January 5, 2017 via  www.dkfz.de/phd

DKFZ-PhD-Program Computational-Cancer-ResearchDKFZ-PhD-Program Epigenetics

 

 

Mathematikon 400pxAs of April 28, you can find all bioinformatics groups of the eilslabs (Computational Oncology, Cancer Regulatory Genomics and Data Management) in the brand new Mathematikon building complex. The eilslabs office are in the central of the three Mathematikon building, the official entrance and adress is Berliner Straße 41. We are looking forward to welcome you soon!

 

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
This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Using the LOV2 domain as a light-sensitive switch, the eilslabs team around PhD Student Dominik Niopek and group leader Barbara Di Ventura managed to induced spatial control of desired proteins in mammalian cells. The tool entitled LEXY (for light-inducible nuclear export system) combines the LOV2 domain with a nuclear export signal sequence (NES) and allows to trigger the nuclear export of attached proteins using blue light. Function of the tool was shown by the light-controlled regulation of synthetic repressors and the transcriptional activity of human p53 with light.

optogenetik 460x175

Source: Dominik Niopek

Microscopy images of human embryonic kidney cells in culture. The cells were genetically modified to produce a glowing protein, which was linked to the new optogenetic tool (the LOV2-NES hybrid). Cells irradiated with a blue laser beam (blue arrows) show an efficient nuclear export of the protein. Non-irradiated cells (red arrows) show a constitutively nuclear localisation of the protein.

LEXY supplements the previously developed tool named LINuS (light-inducible nuclear localization signal), which allows the light-controlled nuclear import of proteins.

Further Reading:

 

 

2016-1 Steinhauser briefingsIn this recently published work, Sebastian Steinhauser and Nils Kurzawa have benchmarked 14 available tools to determine differential enrichment of transcription factor binding between two conditions. The work was part of the Master thesis of Sebastian Steinhauser, which he carried out in the eilslabs under the supervision of Carl Herrmann in the Cancer Regulatory Genomics group.
Their analysis highlights significant differences between the produced results and emphasizes the need for selective choice of the correct tool.

Read more here:
Steinhauser, S., Kurzawa, N., Eils, R., & Herrmann, C. (2016). A comprehensive comparison of tools for differential ChIP-seq analysis. Briefings in Bioinformatics. doi: 10.1093/bib/bbv110

 

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

Jasmin Dehnen and Frieda Anna Sorgenfrei from the igem 2015 team have written a short essay about the creation of Aptabodies in the Laborjournal.

Read more at http://www.laborjournal.de/rubric/methoden/methoden/v159.lasso (only in German!)

aptabody

Copyright: iGEM Team Heidelberg 2015