Skip to main content

Epigenetics and System Biology of Stem cells and Reprogramming

Periodic Reporting for period 1 - EpiSyStem (Epigenetics and System Biology of Stem cells and Reprogramming)

Reporting period: 2018-03-01 to 2020-02-29

In eukaryotic cells, DNA is tightly packaged as chromatin in a form of nucleosomes, comprised of 147 bp of DNA wrapped around two copies each of the core histones H2A, H2B, H3 and H4. Nucleosomes are separated by linker DNA, bound by a linker histone, H1. This primary ‘beads on a string’ structure is further compacted into complex higher-order structures that are not yet fully understood. Chromatin structure is controlled by protein complexes generally called chromatin modifiers, which affect DNA accessibility, DNA-protein interactions and chromatin organization. Chromatin remodelers get recruited to chromatin by a variety of signals - modifications on both DNA and histones - which together formulate an elaborate code, all in the specific context of DNA sequence, spatial organization, developmental stage and tissue specificity.
Chromatin structure, regulation and plasticity dictate many of the nuclear processes, e.g. replication, transcription, cell cycle, protein dynamics, chromatin modifications, and more - all of which ultimately facilitate or repress changes in transcription, either locally or globally. Chromatin is the basic regulatory unit of life and as such, it controls developmental and functional states of all cells, including pluripotency. In recent years, methods to study chromatin have dramatically improved and expanded to genome-wide global approaches, allowing a systems-level understanding of epigenetic regulation

The aim of EpiSyStem network is to concentrate on technological advances and state-of-the-art methods which enable a fresh and unbiased look at some of the long-standing questions in epigenetics. We combine chromatin biology in stem cells, early embryos and reprogramming (including the modelling of human neurological, chromatin-related, diseases) with bioinformatics, epigenetics/epigenomics, and systems biology at the population and the single-cell / single embryo level. This multidisciplinary approach enables a profound training with a deep, systems-level understanding of chromatin biology and epigenetic regulation of stem cells and reprogramming. Our ESRs are trained in state-of-the-art and future technologies, providing them with all the necessary tools, expertise, experience and connections to foster their career development. Our outstanding students (ESRs) investigate the fundamental questions of stem cell biology, epigenetics, chromatin, differentiation and reprogramming, disease modelling, and bioinformatics, with a special emphasis on systems biology of stem cells and chromatin. Our ESRs will receive their PhDs under the framework of this program, absorb a holistic view of the field, with the forefront of research in the field and enjoy exchange programs between labs, workshops on emerging topics in stem cell epigenetics and bioinformatics. Hence, EpiSyStem provides the society better and more professional scientists, with an educational perspective and scientific integrity, understanding the necessity to enhance the public knowledge on scientific issues. Our students participate in various outreach activities and are directly involved with the public on the views and interests related to their research field. EpiSyStem network contributes the public through both knowledge and education.
At the first period of EpiSyStem, there has been significant progress towards the network’s objectives. First and foremost, all the beneficiaries have recruited ESRs in line with the recruitment strategy, and all were enrolled in PhD programmes at the affiliated academic institutions. EpiSyStem puts a strong emphasis on the timely manner of the training events and their content: 1. Summer School at Spetses, Greece (August 2018). 2. Bioinformatics Workshop, Istanbul, Turkey (November 2018). 3. Epigenetics and Chromatin workshop, Munich, Germany (April 2019). 4. MS & Single Cell Workshop, Nijmegen & Utrecht, the Netherlands (July, 2019).
The implementation of the work-plan carried out as planned, including the uploading of the deliverables. The milestones were reached and one paper has already been published online: “Dosage analysis of the 7q11.23 Williams region identifies BAZ1B as a major human gene patterning the modern human face and underlying self-domestication” (10.1126/sciadv.aaw7908) As a direct product of WP4. In addition, our ESRs participated in the writings of several reviews.
EpiSyStem network has already contributed science with two open-access papers and two reviews and plans to continue publishing at high profile scientific journals. In parallel, EpiSyStem will continue to provide a unique ground for learning, centred on the ESRs' training. The workshops, already offered to the fellows, together with the future planned ones, will boost the knowledge of the young researchers, giving them innovative tools and expertise on state-of-the-art methods to implement in their research and future careers. The network enhances their understanding of related fields of study while giving them a broader perspective on science and exposing them to both industrial and academic environments. EpiSyStem equips the ESRs with the required knowledge and tools, opening up a wide range of possibilities and directions for their future.
EpiSyStem provides multiple views of chromatin biology spanning both basic research and industry. Numerous training sessions in methods of chromatin assays, cell cultures of human and non-human organisms, single-cell technologies, and bioinformatics-related technique are already given or planned soon. Our fellows learn to analyse large scale data providing a systems-level view on stem cell epigenetics. We further plan to provide training in advanced techniques, microscopy, bioinformatics, liquid handling systems and more. In our future meetings, we plan to improve the fellows' interrelations and encourage their entrepreneurship skills. We are sure that such it will expand their scientific and interpersonal skills and will make them better scientists, aimed at advancing research skills to the broader community in the future.
EpiSyStem provides multidisciplinary opportunities together with career development sessions that will promote vast interactions between the members, the ESRs and the community, and of the industry-oriented training activities. The structured exchange-of-ideas within EpiSyStem allows collaborations that will surely last beyond the training period and be developed into career interactions. Such associations reflect the basic idea of EpiSyStem: to expose the ESRs to a broad range of disciplines, methods and perspectives, as well as innovation beyond fundamental science and beyond the state-of-the-art. This dual academic and non-academic training should enhance the intersectoral employability of the researchers and thus provide Europe with highly trained individuals, ready to capacitate critical positions both in the industry and academia.
An example from the work of ESR Adrianos Skaros