Key activity

Development of research teams capacities

An integrated research team will be established, consisting of 4 excellent and 3 key workers of the Institute of Biophysics AS CR (IBP), 1 newly hired excellent worker, 2 newly hired key workers (including one foreign worker), 5 newly hired postdocs or PhD. students and a technician. Leadership of the team will belong to an experienced foreign scientist, Prof. Jean-Louis Mergny (JLM) who currently works at IECB in Bordeaux. JLM will work at IBP (work load 0,5; place of work IBP) and will prepare research conception, think through strategy, consult the used methods and results, write publications together with the team members. The team will focus on 4 research topics in the area of studies of nucleic acids structure, their interactions, biological functions and possible therapeutic use. Individual team members will be responsible for these topics. Established team comprises of sufficiently experienced research workers at the level of excellent workers who are able to publish in prestigious journals and belong to respected scientists. In the CR, IBP belongs among the most successful research institutions with high productivity. In that way, top quality of the team within the CR is guaranteed. By connecting the team with strategic partner institution (IECB in Bordeaux) under the leadership of JLM, another significant increase in productivity of this team will occur. Both quality of research at IECB and personal qualities of JLM are indisputable. Therefore, the main objective of the project – establishment of an excellent team in a key field of science – will be fulfilled.

Infrastructure completion, modernization or upgrade

Current state of the instrumentation relevant to this project’s aims (as described in part 4.2.3 of the Feasibility Study) has up to now been convenient for solving individual research topics in separated laboratories and has corresponded to current state-of-the-art in given areas. As the main ambition of this project is to integrate individual topics to coordinated, highly effective research of an interdisciplinary character, it is necessary to adjust the instrumentation by its (a) modernization, (b) widening its capacity and (c) suitable completion (missing instruments, devices and accessories for existing instruments are also mentioned in part 4.2.3). This will widen the range of experimental methods available without any limitations for the project solving and will enable us to study phenomena whose research would be difficult at the current state. Instrumentation that we plan to acquire within this project (in detail in part 4.3.3 of the Feasibility Study) will be purchased in the first year of the project realization (2017) in the shortest possible period (as the regular course of tenders will allow) so that work on the project could be started as soon as possible in a full extent. The only exception comprises the computer clusters, which will be acquired in three waves: 2017 – CZK 3 mil., 2019 - CZK 3 mil. and 2022 - CZK 4 mil. The reason for this is a quick outdating of the computer equipment which is necessary to be renewed continuously so that it is possible to continue and further develop the research in the sustainability period. Moreover, distribution of this investment will allow to use the most up-to-date equipment for the whole time and therefore improve the project’s outputs. Plan of the corresponding tenders is stated in part 8 of the Feasibility study.

Strategic partnership development

Development of international cooperation of the IBP necessary for accomplishment of developmental aims of the centre in areas relevant to research objectives if this project will lie especially in cooperation and development of strategic partnership with IECB (Institut Européen de Chimie et Biologie) in Bordeaux, France (http://www.iecb.u-bordeaux.fr/). This cooperation naturally devolves on engagement of Prof. J.-L. Mergny (who is currently director at IECB) as the leader of the integrated team (KFRW) in this project. From the expert point of view, a natural bond will be created between this project’s team and team led by JLM at IECB (http://www.iecb.u-bordeaux.fr/index.php/en/equipes/unusualnucleic-acid-structures), which is focused on studies of unusual (non-canonic) DNA structures, their interactions and potential therapeutic use. Cooperation with IBP will be based on both-directional exchange stays during which common topics of the project will be solved, on knowledge sharing, mutual training of workers in areas of relevant experimental methods and on submitting common international projects (according to topics also with other foreign partners of both institutions). Specific contribution for the project solving will consist in the access to new ligands recognizing non-canonical structures and in cooperation on their development.

Project management

The realization team will be led by the project coordinator (Miroslav Fojta, MF), who will be superior to the administrative team (AT) and research team (RT). Project will be led by KFRW (J.-L. Mergny), whose main responsibility will be to maintain high standards of scientific research. In the absence of KFRW, the project coordinator (MF) will deputize for him. The research team will further comprise 4 excellent scientific workers, who will manage key activities and research packages, 5 key scientific workers, 5 expert workers and a technician. For detailed description of the organizational structure and roles of individual workers see part 6.3 of the Feasibility Study. Research activities and scientific aims of the project are formulated on the basis of integration of topics of current research activities of excellent scientific workers and are covered by the research activity of KFRW- the team leader J.-L. Mergny. From this fact, also the conception of the research team operation and its management is derived. Each of the excellent scientific workers (except for the project coordinator) will be responsible for solving one research package; nevertheless, regarding the integrating character of the planned research activities, each of these leading workers will also contribute to solving all four WP in an appropriate extent. At the positions of key scientific workers, there will be scientific workers (from the level of postdocs above) with experience in certain research areas and application of specific methods (see following table and part 6.2.2 of the Feasibility Study). Other research team members will be at the level of postdocs, alternatively advanced PhD. students. They will be subordinate to WP leaders according to their research topics (partial projects). Work load for the team members will correspond to the roles of individual workers; leader of the research team (KFRW) and coordinator will have the work load of 0.5, other excellent scientific workers 0.4 and other scientific workers 1.0 in agreement with the fact that they will be devoted solely to the research activity on the project.

Apart from generally obligatory key activities, following key activities will be realized within this project:

1. The main activity will be an interdisciplinary scientific research in the area of structure and interactions of nucleic acids and their roles in regulation of key cell processes in relation to molecular mechanisms of origin and treatment of serious diseases. The research will be coordinated by KFSW prof. J.-L. Mergny and will be focused primarily on characteristics and functions of four-strand alternative structures of RNA and DNA, namely guanine quadruplexes (G4) and cytosine i-motifs. Specific scientific subjects will include: (i) principles of G4/i-motifs formation and their stability, (ii) research of these structures as potential therapeutic targets and their recognition by drugs, (iii) recognition of G4/i-motifs by proteins, (iv) research of mechanisms of evolution of these structures and (v) development of new analytical methods and approaches for studies of these motifs and their interactions with drugs and proteins. Great part of the research activities will also be devoted to studies of possible use of these structures for biotechnological and nanotechnological applications. The research subject will respond to continuously gained results.
2. Natural key activity of the project will be to ensure mobility of human resources within the international strategic partnerships and increase their qualification especially by means of foreign internships, work seminars and participation at international conferences.
3. Integral parts of the project are constituted by activities targeted at groups of students of master and PhD. studies in the realization region, particularly methodical courses and work seminars led by members of the project team. These activities, within which the outputs of the project and methodical background will be made available to other scientists in the region, alternatively to corporate partners, will contribute not only to development of human resources for RDE and ensuring the sustainability of the project in the future but also to interconnection of research activities at academic institutions with activities of industrial partners.