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Joint training and research network on Chromatin Dynamics and the DNA Damage Response

Final Report Summary - ADDRESS (Joint training and research network on Chromatin Dynamics and the DNA Damage Response)


The Program "Joint training and research network On Chromatin Dynamics and the DNA Damage Response” (aDDRess - ITN ) is an FP7-funded Marie Curie Initial Training Network that is coordinated by Prof. George A. Garinis at the Institute of Molecular Biology and Biotechnology (IMBB) Foundation for Research and Technology-Hellas (FORTH) , Heraklion , Crete , Greece.
i. Overview of results.
Addressing the functional role of genome maintenance in development and disease is thought-provoking, challenging and entirely novel. Lack of any mechanistic knowledge in the proposed area originates primarily from current difficulties in dissecting the diverse functional contributions of DNA repair mechanisms in development and disease. Understanding these connections will shed light on vital processes ranging from transcription, genome maintenance and chromosome architecture to how cells communicate and respond at the tissue, organ and organism levels. To tackle these needs, we established the aDDRess-ITN, a program with top-level scientists and highly committed non-academic partners with i. documented excellence on research, ii. long-standing experience in training, iii. cross-disciplinary capabilities on a wide range of genetic model systems (s. cerevisiae, c. elegans, x. laevis, m. musculus, human cells) and iv. expertise in pioneering technologies and cutting edge tools, some of which have been specifically developed by the participants of this Network.
The overall objectives of the aDDRess-ITN are to i. establish a European research platform of excellence in the field of chromatin dynamics and the DDR by integrating research from basic mechanisms to translational research applications, ii. create a Network dedicated for the training of ESR/ERs promoting their independent careers, their own scientific goals and future employment prospects and to transform our current successful, long-term collaborations into a stronger intellectual and training network while building durable links between the participating labs and the industry (SMEs). The aDDRess ITN focuses on a series of relatively short-term objectives that are achievable within the time course of the Network project. These objectives are centered to 13 ESRs and one ER and are grouped into two broad thematic areas: 1. Function of DNA repair/DDR mechanisms in the context of chromatin, 2. DNA repair/DDR mechanisms and chromatin dynamics in cell fate and disease. In addressing these aims, we have put forward a multidisciplinary approach to study this central thematic area at the molecular, cellular and systems level by assembling a group of scientists and industrial partners with cross disciplinary expertise and capabilities. The aDDRess ITN includes several genetic model systems employing cutting-edge technologies and tools, some of which have been specifically developed by the participants of this ITN. This consortium combines top-level, state-of-the-art interdisciplinary research skills ranging from basic molecular mechanisms and ‘omics’ level understanding to translational research and clinical applications. In a nutshell, the aDDRess-ITN Program had several tangible results ranging from posters and publications to oral presentations of partners and fellows at various conferences and meetings allowing us to gain insights into i. the functional interplay between the systems engaged at repairing the DNA damage and the chromatin structure and composition and on ii) how (defective) DNA repair/DDR mechanisms dictate cell fate and disease. In terms of training, the aDDRess-ITN training program fully succeeded in establishing two main modules (the Local Training Module and the Network-wide Training Module), with distinct and overlapping training nodes. The Program allowed fellows to gain general expertise in Biochemistry, Molecular/Cell Biology and Genetics. It also allowed the fellows to gain specific expertise to the field of the Network (DNA repair/DDR mechanisms, structure and function of chromatin, high-throughput (epi)genomics and transcriptome profiling, mass spectrometry/proteomics methodologies, genetic manipulation and knockdown technologies, bioinformatics and pre-clinical evaluation studies. In parallel, the program provided expertise to Complementary skills courses and seminars were rich in content and well structured; such courses included lectures on the dissemination of scientific ideas or results in oral and written form, project management skills, intellectual property protection, and technology transfer in the industry and commercial valorization of the results, animal welfare, legislation and bioethics.
Conclusions: the Program fully succeeded in accomplishing the end objectives of the project as a whole. The aDDRess-ITN improved fourteen young scientists’ career prospects, introduced young scientists to the Industry, enhanced public-private sector collaborations, established a lasting structured training program, stimulated inter-sectorial mobility, strengthened the European human potential in research, contributed to the development of the European Research base and generated novel scientific information.
Socioeconomical impact of results: With an ever-growing proportion of elderly people in Western societies, there is an immense pressure to identify strategies to prevent or delay age-associated frailty and disease that is imperative for maintaining the health of our population, as well as European economy. However, in order to develop therapeutic strategies for delaying age-related pathology, a better understanding of the underlying causes of aging is required. The almost exclusive link between an extending class of syndromes with phenotypes resembling accelerated ageing and inborn DNA repair defects points to genomic damage as a major culprit in aging. These critical outcomes of DNA damage and age-related diseases represent dominant health care problems in modern societies stressing the enormous medical impact of genome (in)stability. The Program generated a wealth of published information on how cells regulate replication and transcription upon DNA damage, on the functional links between replisome stability and histone dynamics, on the chromatin remodeling during DNA repair, on NER-associated chromatin modifications, the role of NER factors in development and disease as well as the immunophenotype of NER progeroid mice, the epigenetics of DNA repair and its role in aging or the generation of novel bioinformatics tools for biomarker discovery in NER progeria. Such an active research and interdisciplinary training program in the field of genome maintenance mechanisms was timely from the perspective of the European Community’s desire to enhance the research base in areas relevant to quality of life. The aDDRes-ITN allowed us to get insights into the causes of DNA damage-driven pathologies (e.g. cancer, age-related dysfunction) and identifying new pharmaceuticals against age-related pathologies, including carcinogenesis. The latter is a growth area of strategic and financial importance to Europe as a whole.
Impact on fellows’ careers: Following the completion of the aDDRess-ITN Program, our fellows gained strong backgrounds in genetics, molecular and cellular biology, genomics, bioinformatics and proteomics in organisms ranging from yeasts to mammals. Within SMEs, the ESR/ERs received extensive training in cutting-edge methodologies, such as mammalian genetics, high-throughput gene technologies, ChIP-, bioinformatics- and proteomics-based approaches as well as expertise in complementary skills. We appreciate that the long-term implications on the fellows’ career prospects have been significant: the training program enabled all fellows to develop and/or further extend a solid scientific basis and critical judgment, ensured that the fellows graduate as a new breed of scientists trained in facing the challenges of contemporary post-genomic biology and enabled the ESRs to tackle issues that are relevant no matter what path their research or professional careers will take, e.g. technology transfer or clinical studies etc. It is also our appreciation that the aDDRess ITN offered the opportunity to significantly enhance existing institutional efforts in training and research, to build up long-term, extensive synergies beyond the conclusion of the ITN program, to include laboratories and young scientists from the less-favored European regions and to integrate the existing scientific and training activities into a larger durable European partnership. With respect to the SMEs, the program has brought Biomedcode and ATLAS Biolabs closer to academia, enhanced their R&D programs and allowed them to raise further capital through future collaborative research programs.

Network website:

Coordinator contact details:
George A. Garinis
Professor, University of Crete
Group leader, IMBB-FORTH
Institute of Molecular Biology and Biotechnology
Foundation for Research and Technology - Hellas
Nikolaou Plastira 100
GR-70013, Heraklion, Crete
Tel: +30 2810 391246
Fax:+30 2810 391101