Systems Biology of Health in Old Age (Systembiologie für die Gesundheit im Alter – GerontoSys2)

Biotechnology (Biotechnologie - Chancen nutzen und gestalten)

2009-2016

32,7 Million Euro (total)

Federal Ministry of Education and Research – Ref. 614

In the field of basic research for the life sciences, the Federal Ministry of Education and Research (BMBF) intends to consolidate Germany's successful position in systems biology by establishing suitable research structures, focusing national expertise and selectively supporting young scientists. This funding guideline will ensure that systems biology research into the biological causes of ageing will be sustainably funded in order to make a further contribution towards establishing personalized medicine.Demographic change, continuous increase in life expectancy and altered lifestyles lead to new challenges for society, politics and science. The occurrence of various diseases such as dementia, metabolic illnesses and various forms of cancer is closely linked to age. In this way, increasing life expectancy does not only lead to an overall increase in the number of sick people but also to the probability of multiple morbidity or chronic disease. Important research aims therefore consist of understanding the biological processes that underlie ageing and clarifying their significance in the development of age-related diseases. An understanding of these biological processes will create the foundations and prerequisites required to prevent and combat age-related diseases more effectively, thus ensuring a high level of health and self-determination up to a ripe old age. Apart from hereditary factors, external parameters arising for instance from the environment, nutrition or else individual behaviour, influence how long a person remains healthy. New research approaches are required in order to understand the complex biology of ageing processes and their interdependence with age-related illnesses. These approaches must go beyond classical experimental studies on single components, individual stages and sub-mechanisms, and be in a position to systematically record and analyse the complex interaction of age-related factors. The research approach of systems biology has the goal of defining these parameters with respect to their effect and also to analyse and model biological organizational levels in a holistic manner. Over and above a purely static acquisition of molecular data, particular consideration is given to the dynamics of the process as a whole. Optimized models will allow predictions to be made on the behaviour of a system, which in turn will make patient-oriented diagnoses possible, as well as more efficient preventative measures and a more effective treatment of diseases. This research approach is expected to make a significant contribution towards clarifying the ageing process, and in the medium to long term to facilitate progress towards “healthy ageing”. Today, our understanding of many cellular and molecular ageing processes is so advanced that a wide variety of starting points already exist for a systems biology approach. Starting from the molecular level, other biological organizational levels, such as compartment, cell, tissue, and organ, are incorporated into the investigations. Findings obtained using model organisms can be compared with data from human samples. Systems biology models on a cellular level also provide the basis for advances in the field of polypharmacy. Particular note should be taken of the fact that systems biology models play an important role in translating research results into clinical practice.

The present funding measure “Systems Biology for Health in Old Age – GerontoSys2” thus complements and extends the existing GerontoSys measure. The measure is intended to identify one or two other research cores and also to take up issues that have not yet received sufficient attention. An important aspect is also the funding of young scientists in the field of a “systems biology approach for age research”. It is intended to identify those mechanisms that form the basis of the ageing process and to combine the scientific findings into an overall picture. This will then be used as a basis to identify the causal factors that contribute to age-related diseases and to incorporate them into the development of customized preventative measures, of new diagnostic technologies and therapeutic applications adapted to the ageing process. This will give rise to fields of action for different industrial sectors such as the pharmaceutical or food industries. The present measure is embedded in the activities of the Federal Ministry of Education and Research (BMBF) related to research for an ageing society and to the promotion of systems biology in Germany. In particular, it builds on broad and internationally visible medically oriented genome research, and it draws on the funding measures “Systems Biology of Liver Cells - HepatoSys” and “Medical Systems Biology – MedSys”. The systems biology centres already established as part of the BMBF funding measure “Research Units of Systems Biology – FORSYS” and also the existing research core of systems biology for healthy ageing will play an important part in GerontoSys2. The funding measure GerontoSys2 is part of the “Health Research” innovation field in the German Federal Government’s High-Tech Strategy. It addresses current biodemographic developments and initiates research activities for applications in medicine, in basic research, in the field of prevention, regeneration and translation. The new funding measure also provides an important contribution to the “Pharmaceuticals Initiative for Germany”. It supports the goal of further improving patient care in Germany and encouraging innovative research for a healthy and secure life.

A basic prerequisite for all projects is a balanced combination of systems biology and age research. The research approach of systems biology is characterized by a collaborative way of working in the form of cooperations between different disciplines – from engineering, information sciences and mathematics up to chemistry, biology and medicine. The heart of the systems biology approach is an iterative process between laboratory experiments and mathematical modelling using computers. Based on large volumes of quantitative data, algorithms are used to create models, which allow predictions to be made on the behaviour of complex biological systems with the aim of gaining an overall understanding of the system. Funding is provided for: A) Up to two systems biology research cores for health in old age: Creation of interdisciplinary and collaboratively organized systems biology research cores for health in old age at universities or non-university research institutions that bring relevant core competencies together under one roof. B) Application-oriented cooperation projects: In an interdisciplinary approach consisting of theory and experiment, innovative systems biology issues that are highly relevant for health in old age will be addressed. The involvement of industrial companies underlines the application orientation of the approach (see 2.1.2). C) Up to ten Young Investigators Groups on age research based on a systems biology approach. This measure is particularly intended to give young scientists from Germany and abroad with relevant experience in systems biology and/or ageing research the opportunity to work on new research approaches driven by systems biology in a research group and thus to extend their scientific experience. Projects should address topics related to the key processes of ageing or the emergence of age-related diseases using a systems biology research approach (see Section 1.1). In doing so, they should take organic aspects into account. Clearly defined issues should be addressed aiming at an intersystem mechanism-oriented or signalling-pathway-oriented modelling. These issues should be investigated on the basis of exact and robust data. The projects to be worked on should build on existing data where possible, although quantitative data may be collected within the framework of a project. In order to allow pathophysiologically relevant situations to be transferred to humans, not only model organisms should be used but also human systems and patient populations wherever possible. The approaches should not focus exclusively or at least not primarily on specific disease entities or indication fields. The following are examples of possible topics: - Identification of longevity genes and the related metabolic pathways and the modulators of these pathways - Biomarkers for ageing - Cellular repair mechanisms and regeneration processes - Stem cell research concerning age-related changes - Translation models - Influence of specific environmental factors (e.g. alimentary factors) on key processes - Identification and validation of target structures for therapeutic interventions - Multi-generation studies and time series analyses on ageing processes   The following will not be funded: - Purely clinical studies - Purely qualitative investigations - Purely cell-culture-based systems - Exclusive focus on the question “why does ageing occur?” without taking ageing mechanisms into account Research cores and Young Investigators Groups will receive funding for a period of five years; cooperation projects for a period of three years. Small and medium enterprises (SMEs) are particularly welcome to apply. Should scientific services be required within the framework of the project, service providers from industry should be given first refusal.

2.1.1 Research Cores Systems biology research cores for health in old age should bring together the required disciplines (for example, biology or medicine, mathematics, computer science, physics, chemistry, engineering) “under one roof” in an interdisciplinary and collaboratively organized network. Existing and internationally proven expertise in relevant research and development fields should be incorporated (including suitable expertise obtained through other measures funded by BMBF, German Research Foundation (DFG), EC or other funding agencies in the fields of age research, systems biology, bioinformatics, genome and proteome research). Above all, research cores should also uphold the sustainability of the funding measures. The submission of a sustainability concept for such research cores is therefore particularly advantageous for the process according to Section 7. One of the components of such a sustainability concept should be measures for creating sustainability, which are to be contributed by the supporting institutions. Examples include taking over responsibility for staff positions, making buildings available for the expansion of the research core, or making other financial resources available after termination of the BMBF funding measure. Above and beyond this, one of the tasks of the research cores may be their function as central platforms for systems biology research on health in old age. In this context, they should provide sophisticated and cost-intensive technologies such as the chemical analysis of post-translational protein modifications or other infrastructure such as animal breeding facilities, etc. Industrial companies are requested to participate in a suitable manner in the creation of such research units. Funding is available for up to two such research cores.   2.1.2 Application-Oriented Cooperation Projects Within the framework of these guidelines, research projects between academic partners and companies, and those between academic partners are eligible for funding. Collaborative projects are expected to combine the interdisciplinary expertise necessary to achieve the research goals. The number of partners in this type of collaborative project will be determined by the subject matter (see Section 2.2). The partners should be physically near each other and the involvement of industry is preferable, although these aspects are not a prerequisite for funding. German and foreign project partners may jointly apply for funding if the involvement of the foreign partners is necessary and if the foreign partners have secure funding for their part of the project.   2.1.3 GerontoSys2 Young Investigators Groups The aim of “GerontoSys2 Young Investigators Groups” is to attract German or foreign scientists who already have a PhD or postdoc qualification (Habilitation). It is only possible to apply for the creation of a Young Investigators Group via the respective university or research institution. Young scientists who are interested in applying for a Young Investigators Group must therefore first reach an agreement with a university or research institute that can accommodate them. With respect to the project topic, the expertise of the young scientist should complement the spectrum of topics at the host institution. On the basis of the collective wage agreement currently in force, for the period of funding it is possible to provide funding within the framework of the project for the position of the group leader with up to salary grade E14 of the Collective Agreement for the Civil Service (TVöD), for other scientific personnel up to 1 position each in salary grade E13 TVöD (postdoc) and up to two positions in grade 13/2 TVöD (PhD students) as well as the necessary technical staff if applicable. It is not possible to fund positions that are financed from basic funds. Expenditure for equipment and investments or travelling expenses will be reimbursed according to the provisions of the other terms and conditions for the awarding of grants currently in force. Funding is available for up to ten such Young Investigators Groups.

Research projects under A, B and C must be planned as interdisciplinary projects from the beginning, i.e. theoretical (e.g. mathematical modelling, bioinformatics) and experimental fields (e.g. molecular biology, cell biology, medicine, genetics, biochemistry) must be incorporated into the project planning simultaneously and in a well-balanced ratio. Other disciplines (e.g. theoretical physics, sociology, biostatistics/demography) may also be incorporated depending on the requirements of the subject matter.   Research Cores and Application-oriented Cooperation Projects Organizations eligible to apply for funding are institutions of higher education, non-university research establishments, and commercial companies with their headquarters in Germany, particularly SMEs (the European Community’s definition of SME can be found at: http://ec.europa.eu/enterprise/glossary/index_en.htm Research institutions that receive their basic funding jointly from the German Federal Government and the federal states will only be granted project funds supplementing their basic funding for their additional expenses under certain conditions. GerontoSys2 Young Investigators Groups Organizations eligible to apply for funding are institutions of higher education and non-university research establishments. Research institutions that receive their basic funding jointly from the German Federal Government and the federal states will only be granted project funds supplementing their basic funding for their additional expenses under certain conditions.

Funding is provided for projects as non-reimbursed payments. Funding duration depends on type of project: 1.) Research cores: Funding for 3 years, After a positive evaluation extension for another 2 years. 2.) Collaboration projects: Funding for 3 years. 3.) Young investigators group: Funding for 5 years. The level of funding is dependent on the described necessary budget to fulfil the project aims.

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