Description
Increasing evidence indicates that proteins playing a structural role in the architecture of the cell nucleus are also involved in orchestration of key nuclear processes such as DNA replication, transcription or DNA repair. NuArch is based on the hypothesis that proteins resident in different nuclear compartments have i) roles in local gene regulation and ii) play a role in autophagy and DNA damage repair processes. Co-operation will be realized on the level of exchange of knowledge, experimental approaches and mobility of students or post-docs organizing common practical workshops. We expect complementary competences in different areas of life sciences to build an interdisciplinary effort. Target groups will be students and particularly postdocs supported by the program. We will also aim to make our findings significant and attractive for clinical laboratories. Partners guarantee joint co-operation and exchanged of knowledge. NuArch will lay the ground for a more permanent cooperation framework and exchange system between partners beyond the project duration.
Summary of project results
The project NuArch was expected to establish new roles for known nuclear structural proteins and linked them to key nuclear processes critical for cellular homeostasis and regulation of cell and tissue growth. Project also sheds a new light on several nuclear proteins known to be implicated in a variety of rare diseases collectively referred as “nuclear envelopathies”. These affect a range of different tissues to give cardiac and skeletal myopathies, partial lipodystrophy, peripheral neuropathy and premature aging. The project especially aimed at proteins resident in different nuclear compartments (the nuclear envelope and the nuclear matrix) that might played i) roles in local gene expression regulation at the nuclear periphery and ii) new, unexplored roles in autophagy and DNA damage repair (DDR). Defects in these proteins are likely to result in defective autophagy and DDR signalling. To reach the objectives, we used a combination of complementary approaches from different areas of the biomedical sciences such as protein and chromatin immunoprecipitation or advanced live cell imaging. During the years 2014-2017 we published 14 papers with project dedication. NuArch is a basic science project, thus no applications in clinical practice were considered as aims of the project. However, our project deals directly with the biology of diseases including cancer, laminopathies, and experimental models of schizophrenia. Thus, our findings could contribute to novel therapeutic modalities, especially in cancer radiotherapy and schizophrenia treatment by clinically used inhibitors of histone modifying enzymes, including histone acetyltransferases (HDACs).
Summary of bilateral results
The NuArch was a basic science project, thus no applications in clinical practice were fulfilled. However, our scientific activities dealt directly with the biology of diseases including cancer, laminopathies, and experimental animal model of schizophrenia. Thus, our findings could contribute to a novel therapeutic approaches, especially in cancer radiotherapy and schizophrenia treatment by clinically used inhibitors of histone modifying enzymes. The consortium combined complementary competences in different areas of life sciences to build an interdisciplinary effort required to achieve the ambitious and thought-provoking goal of implicating nuclear proteins in autophagy, gene expression and DNA damage repair. Scientists with outstanding knowledge and technical expertise in their respective fields (DNA damage repair and advanced live cell imaging, nuclear envelope biology and chromatin immunoprecipitation, autophagy) are associated to fulfil the multiple aspects of NuArch aims. The NuArch project increased cooperation and complementarity between the Czech and Norwegian research groups. We shared laboratory techniques and approaches, especially a knowledge on high resolution microscopy and chromatin immunoprecipitation techniques. Through the project we were able to published 14 scientific papers (with IF). We introduced and discussed our data at numerous scientific conferences and workshops. Project was also advertised via public media, such as newspaper Brněnský deník, Rovnost or in Czech magazine Vesmír, publishing science in a popular way. Joint scientific workshops were especially aimed at young scientists and students (diploma and Ph.D. students from Masaryk University in Brno represented a substantial part of this international project).