A) Summary presentation of the technical content of the grant application The objective of the Strategic Workshop (in cooperation with SE’s excellent researchers) is to explore how peptidergic regulation and signalling is involved in the maintenance of homeostasis and in the development of high-frequency systemic diseases, created by the “excellence” working groups of PTE and DE. To achieve this, the Workshop intends to establish a completely original approach, which examines the role of endogenous peptides in the pathology, diagnosis, prevention and personalised therapy of diseases along the matrix-like complexity of the processes determining physiological and pathological functions (communication, protection, nutration, regeneration). The main reason for the failure of previous drug development strategies for neuropeptides was that there was a huge translational deficiency (‘gap’) between experimental paradigms and clinical situations, with specific peptides and their receptors isolated only in individual systems and lack of systemic, complex approaches. The aim of this programme is an integrative system analysis, which can help to eliminate a significant number of previous problems. By using the multidisciplinary platform to be presented, the project contributes significantly to strengthening the R & D capacity of the Hungarian knowledge bases and to producing high-quality research results at international level. Introduction The basic condition for the homeostatic balance of the organism is the physiological functioning of the organs that make up the organism (Function). The general and organ-specific functions are essentially determined by the networked operation of four continuous, multi-directional, complex process sequences: — Communication: Intercellular communication of neuronal and non-neuronic cellular elements with direct, humoral (mediators) and particular (vescules) connectivity — protection: Systemic defence response to external and internal and hazard signals provided by the interaction of resident and inflowing immune cells and nerve elements — Nutrition: Qualitative and quantitative conditions (whether or not broken down by tissue and cellular level) of satisfactory nutrient supply of the organ — Regeneration: Basal and induced cell replacement and tissue regeneration to ensure the functioning of the organ If any of the above processes are damaged, this leads to homeostasis overturning and thus to the development of a specific disease. Due to the complexity of the body, pathological responses in most cases are not limited to a single organ, but cause the development of systemic diseases. These include chronic, multi-organ system disorders (and severe complications thereof) that affect the quality of life of large populations with inflammation, abnormal immunity and pain, such as multi-joint inflammation (rheumatoid arthritis), psoriasis, systemic lupus, scleroderma and fibromyalgia. Although considerable efforts have been made to identify pathological pathologies, but still only partial results, it can be clearly stated that the treatment of these diseases is not resolved and therefore constitutes a major social and economic problem. The importance of peptidergic signalling — Problem assessment The summaries published in leading international journals in recent years highlight the fact that biomedical research currently has a “decade of peptides” as these mediators carry out tonic and diversified regulation of the functioning of many organ systems and, on this basis, influencing these mechanisms in systemic diseases can provide common therapeutic opportunities. Neuropeptides are one of the most common humoral elements of the body. Previous results of the Workshop participants provided evidence that certain peptides (e.g. pituitary adenylate cyclase activating peptide (PACAP), somatostatin, tachyquinines, endotelin-1) play a determining role in intercellular communication and inflammatory and immune processes. We also have data on the ability of some peptides to control the responsiveness of blood vessels and the differentiation of cell growth. It was also found that the levels of certain neuropeptides are significantly altered in these systemic diseases. At the same time, there is a marked paradigm shift in the study of the peptidergic system today: most “neuro” peptides in the classical sense have recently been found to be produced in many non-neuronic cell types. This significant discovery raises many questions, dilemmas and problems. It is not known to what extent and pattern the peptides of neural and non-neuronic origin are involved in the regulation of the homeostatic functions of a given organ, or by what cell-specific function (similar or different) is used. Thus, it is not clear what the systemic significance of peptides is