Final Report Summary - BERG (BERG – Biomedical Epigenomics Research Group)
Background. The genetic code of the DNA provides a universal building plan for the cell’s molecular machinery. But a second code is needed to control the complexity of the human body, organizing 100 billion cells with identical genomes into 200 specialized cell types. This second code is called “epigenetic”. Defects in the epigenetic code play an important role in cancer, and they create an opportunity for new therapies.
State-of-the art. Experimental and computational methods are now available to support epigenome mapping in clinical samples. Nevertheless, our understanding of the role of epigenetic alterations in leukemia is still very sketchy and incomplete.
Project objectives. The BERG project pursues three aims:
Aim 1. Establish an epigenome research platform addressing biomedical questions (technology development)
Aim 2. Dissect the epigenome dynamics of leukemia progression (disease mechanisms & diagnostics)
Aim 3. Rational design of epigenetic combination therapies for cancer (drug effects & genomic medicine)
Key results. Given the supplementary character of the CIG funding scheme, this progress report covers all results that are within the scope of the BERG project, independent of whether or not they were funded by this specific grant or by other sources.
1. Completion of the epigenome research platform at CeMM and its initial application in biomedical research
Relevant Publications:
http://dx.doi.org/10.1016/j.tibtech.2016.04.004
http://dx.doi.org/10.1016/j.stem.2016.10.019
http://dx.doi.org/10.1126/science.aaf4238
2. Dissection of epigenome dynamics in leukemia (CLL) and other cancers (Ewing sarcoma, glioblastoma)
Relevant Publications:
http://dx.doi.org/10.1038/ncomms11938
http://dx.doi.org/10.1038/nm.4273
http://dx.doi.org/10.1101/173864
3. Methods development for the rational design of epigenetic combination therapies
Relevant Publications:
http://dx.doi.org/10.1038/nmeth.4177
http://dx.doi.org/10.1093/bioinformatics/btv612
http://dx.doi.org/10.15252/msb.20166890
Impact. The project has established a strong foundation of epigenomics applied to biomedical research in Austria. Over the course of the research BERG project, the grant’s principal investigator has published 15 publications as senior or joint-senior author, which appeared in high-impact journals such as Cell Stem Cell, Nature Biotechnology, Nature Medicine, Nature Methods, and Science. He has also contributed as a co-author to a total of 29 publications, broadening the use of epigenomics and next generation sequencing technology in Austria and beyond. Finally, the project has contributed to highly visible outreach activities, including a “World View” article on personal freedom in networked societies published in Nature.
Career development and integration. The grant’s principal investigator has successfully established his scientific career in Austria. He is an independent research group leader with principal investigator status at the host institution (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences) and a guest professor at the Medical University of Vienna. He currently supervises a research group comprising five PhD students, five postdocs, and two technicians. He has successfully competed for several national and European research grants, including a “New Frontiers Group” award (2015 – 2020) by the Austrian Academy of Sciences and an ERC Starting Grant by the European Research Council (2016 – 2021). He has recently received the International Society for Computational Biology (ISCB) Overton Prize, the international research prize that is given to one early-to-mid career scientist each year who is recognized as an emerging leader in bioinformatics.
State-of-the art. Experimental and computational methods are now available to support epigenome mapping in clinical samples. Nevertheless, our understanding of the role of epigenetic alterations in leukemia is still very sketchy and incomplete.
Project objectives. The BERG project pursues three aims:
Aim 1. Establish an epigenome research platform addressing biomedical questions (technology development)
Aim 2. Dissect the epigenome dynamics of leukemia progression (disease mechanisms & diagnostics)
Aim 3. Rational design of epigenetic combination therapies for cancer (drug effects & genomic medicine)
Key results. Given the supplementary character of the CIG funding scheme, this progress report covers all results that are within the scope of the BERG project, independent of whether or not they were funded by this specific grant or by other sources.
1. Completion of the epigenome research platform at CeMM and its initial application in biomedical research
Relevant Publications:
http://dx.doi.org/10.1016/j.tibtech.2016.04.004
http://dx.doi.org/10.1016/j.stem.2016.10.019
http://dx.doi.org/10.1126/science.aaf4238
2. Dissection of epigenome dynamics in leukemia (CLL) and other cancers (Ewing sarcoma, glioblastoma)
Relevant Publications:
http://dx.doi.org/10.1038/ncomms11938
http://dx.doi.org/10.1038/nm.4273
http://dx.doi.org/10.1101/173864
3. Methods development for the rational design of epigenetic combination therapies
Relevant Publications:
http://dx.doi.org/10.1038/nmeth.4177
http://dx.doi.org/10.1093/bioinformatics/btv612
http://dx.doi.org/10.15252/msb.20166890
Impact. The project has established a strong foundation of epigenomics applied to biomedical research in Austria. Over the course of the research BERG project, the grant’s principal investigator has published 15 publications as senior or joint-senior author, which appeared in high-impact journals such as Cell Stem Cell, Nature Biotechnology, Nature Medicine, Nature Methods, and Science. He has also contributed as a co-author to a total of 29 publications, broadening the use of epigenomics and next generation sequencing technology in Austria and beyond. Finally, the project has contributed to highly visible outreach activities, including a “World View” article on personal freedom in networked societies published in Nature.
Career development and integration. The grant’s principal investigator has successfully established his scientific career in Austria. He is an independent research group leader with principal investigator status at the host institution (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences) and a guest professor at the Medical University of Vienna. He currently supervises a research group comprising five PhD students, five postdocs, and two technicians. He has successfully competed for several national and European research grants, including a “New Frontiers Group” award (2015 – 2020) by the Austrian Academy of Sciences and an ERC Starting Grant by the European Research Council (2016 – 2021). He has recently received the International Society for Computational Biology (ISCB) Overton Prize, the international research prize that is given to one early-to-mid career scientist each year who is recognized as an emerging leader in bioinformatics.