Amyloid aggregation is of outstanding biomedical, bio- and structural-chemical importance and has attracted continued interest over the past decades (B.S. Blumberg and D.C. Gajdusek for Kuru’s disease (1976) and S.B. Prusiner for prion heritage understanding (1997) received the Nobel Medical Prize). Scientific breakthroughs in this area can only be achieved if there is a high degree of synergy between researchers, critical numbers and resources. The necessary synthetic, biochemical, spectroscopic, modelling, bioanalytical and nanotechnology capacity is now available at ELTE TTK. Our focus is the development of protein test systems, the rational design, in vitro/vivo production and development of biocompatible nanosystems. In order to achieve our research goals, we intend to establish a centre of excellence, which can bring significant breakthroughs in the field due to the development of cooperation across the whole field of molecular biochemistry, combining six different approaches and six different perspectives. Understanding the spatial structure and dynamics of proteins is a research task that is of biomedical, social and economic importance beyond chemical curiosity and importance. Proteins can be identified in almost all parts of living organisms and function effectively, in accordance with their environment, as complex systems, with well-regulated protein-protein interactions in the background, and with oligo and polymerisation processes (Tory, Perczel, Nature Genetics 2014). However, these processes sometimes lead to aggregation and amyloid dead ends. The change in conformation, which has been diagnosed by Alois Alzheimer for more than 100 years but has not yet been accurately understood on a molecular level, is only one of the amyloid aggregations experienced in the process of ‘protein ageing’. Aggregation is a thermodynamically beneficiary (Perczel 2007), and its detailed understanding and use are central elements of our application. In addition to abnormal protein aggregation, a number of non-pathogenic aggregations are also known. Functional amyloids have played an important role in evolution in bacteria (Pseudomonas), cloak proteins (Plasmodium), spider silk, biofilms, adhesion proteins, etc.; they are distinguished by their stability, flexibility, tensile strength. Our application builds on the novel and goal-oriented linking of six research groups of the ELTE TTK with different scientific backgrounds and operating with outstanding results. The integrated theoretical, experimental and instrumental research team can realise the design, synthesis and extensive examination of peptide and protein-based nanosystems, in which the ß-reflecting spatial structure prone to aggregation is a common element. Biomolecules of this spatial structure include amyloid, spherical zipper, and adhesiv ß-fibres and filaments. They have both potential for material science (self-organised, compact nanosystems, biocompatible adhesives) and can address the serious challenges of life sciences such as Alzheimer’s (APP › ß1-42 aggregation) and Parkinson’s disease (aggregation of?-synuclein), diabetes mellitus (IAPP aggregation) or cancer type caused by underactive tumour suppressor p53 due to aggregation (Knowles 2014). The coordination of preparative, spectroscopic and crystallographic research in the six groups (Perczel), quantum chemistry (the Emperor) and mathematical (Grolmus) modelling, colloidal chemistry (Kiss), directed peptide and protein evolution tests (Pál) and in vivo genetic works (Vellai) allow the development of a focused yet ambitious research at ELTE. All of these applicants have been active and effective researchers for decades (cumulative data: >1000 announcements, >20000 references, >30 years of research experience abroad, >40 PhD students) who manage 5-20 in silico, in vitro and in vivo research support teams, lead MTA-ELTE research team, operate NMR, X-ray, ECD, VCD, AFM, SPR, SEM devices. Although hundreds of proteins have been described as spontaneously forming amyloids in physiological or slightly different circumstances, the molecular details and kinetic parameters of the processes are largely unknown — only occasional light scattering, fluorescence and EM data can be used. (In the course of our control studies prior to the preparation of the application plan, in the case of a variant of a peptide medicine (exenatide) used to cure type 2 diabetes, we discovered amyloid training that could be triggered by environmental changes — a unique test system that could be the ‘benchmark’ system of amyloid transformation). Using spectroscopic (ECD, VCD) and NMR methods, we intend to collect amino acid-specific information on details of amyloidal training, which can lead to the development of a “amyloid recognition” spectroscopy protocol. We intend to examine the protection against specific sequences by means of white octarography using “naturally” acilpeptide involved in the breakdown of the amyloid β-p...