Descripción del proyecto
MATHEMATICAL MODELS ARE CENTRAL IN SYSTEMS BIOLOGY AND PROVIDE NEW WAYS TO UNDERSTAND THE FUNCTION OF BIOLOGICAL SYSTEMS, HELPING IN THE GENERATION OF NOVEL AND TESTABLE HYPOTHESES, AND SUPPORTING A RATIONAL FRAMEWORK FOR POSSIBLE WAYS OF INTERVENTION, LIKE IN E,G, GENETIC ENGINEERING FOR IMPROVED INDUSTRIAL BIOTECHNOLOGICAL PRODUCTION, DRUG DEVELOPMENT OR TREATMENT OF DISEASES, SINCE THE AMOUNT AND QUALITY OF EXPERIMENTAL OMICS DATA CONTINUE TO INCREASE RAPIDLY, THERE IS GREAT NEED OF METHODS FOR PROPER MODEL BUILDING AND ANALYSIS WHICH CAN HANDLE THIS COMPLEXITY, IN THIS PROJECT, WE WILL FOCUS ON MULTI-SCALE MODELLING OF BIOLOGICAL SYSTEMS, I,E, MODELS WHICH INCLUDE DIFFERENT SCALES, FROM MICRO (E,G, MODELS OF METABOLIC NETWORKS) TO MACRO (E,G, BIOPROCESS MODELS USED IN THE CONTEXT OF THE PROCESS ANALYTIC TECHNOLOGIES (PAT) FOR SCREENING, STATISTICAL MONITORING AND CONTROL), THE PROJECT AIMS TO DEVELOP AND APPLY NEW METHODS AND TOOLS FOR BUILDING AND ANALYZING MULTI-SCALE MODELS FROM UNCERTAIN DATA, TYPICALLY EITHER SCARCE HIGHLY INFORMATIVE OR ABUNDANT YET LOW INFORMATIVE DATA, FOCUSING ON THE FOLLOWING RESEARCH PILLARS: (I) MODEL BUILDING METHODS AND TOOLS, INCLUDING IDENTIFIABILITY ANALYSIS, PARAMETER ESTIMATION (MODEL CALIBRATION), UNCERTAINTY MODELLING AND OPTIMAL EXPERIMENTAL DESIGN, ANALYSIS OF HOW TO CONNECT BOTTOM-UP WITH TOP-DOWN APPROACHES, DATA-DRIVEN KNOWLEDGE VERSUS MODEL-DRIVEN ONE, AND COMPATIBILITY AMONG MODELS AT DIFFERENT ABSTRACTION LEVELS,(II) MODEL ANALYSIS METHODS AND TOOLS, INCLUDING GLOBAL SENSITIVITY ANALYSIS, BIFURCATION ANALYSIS, DYNAMIC FLUX BALANCE ANALYSIS, ELEMENTARY FLUX MODE ANALYSIS, AND MODEL REDUCTION TECHNIQUES,(III) APPLICATION TO BIOTECHNOLOGICAL INDUSTRIAL PRODUCTION, WITH SPECIAL EMPHASIS ON HOW LOW LEVEL BIOLOGICAL INFORMATION OBTAINED IN THE PREVIOUS PILLARS CAN PROVIDE VALUABLE INFORMATION AT THE BIOREACTOR LEVEL, IN THIS POINT, IT WILL BE A PRINCIPAL CONCERN HOW TO INTEGRATE DATA FROM ALL SCALES INTO THE PAT FRAMEWORK PROMOTED BY THE FOOD AND DRUG ADMINISTRATION (FDA) IN USA, NAMELY IN STATISTICAL MONITORING AND CONTROL ACTIONS,THESE NEW METHODS AND TOOLS WILL BE ILLUSTRATED WITH A REAL INDUSTRIAL APPLICATION, THE COMPANY BIOPOLIS S,L, WILL BE ACTING AS AN ACTIVELY PARTICIPATING PROMOTING ENTITY (EPO) IN THIS PROJECT, AND IT WILL PROVIDE ACCESS AND COMMIT RESOURCES REGARDING ITS STATE-OF-THE-ART BIOPROCESSING AND FERMENTATION FACILITIES, ANALYTICAL EQUIPMENT AND BIOPRODUCTION KNOW-HOW, TOOLS AND METHODOLOGIES DEVELOPED WITHIN THE PROJECT WILL BE APPLIED CONSIDERING THE ANALYSIS AND CONTROL OF RECOMBINANT PROTEIN PRODUCTION IN BACTERIAL (E, COLI) AND EUKARYOTIC (P, PASTORIS) INDUCIBLE SYSTEMS, EVENTUALLY, THIS WILL ALLOW THE VALIDATION OF THE RESEARCH DEVELOPED IN THE FIRST TWO PILLARS ENABLING A SHIFT FROM THE TRADITIONAL TRIAL AND ERROR DEVELOPMENT AND OPERATIONAL APPROACHES TOWARDS A MORE SYSTEMIC AND RATIONAL APPROACH, modelado multi-escala\biología de sistemas\optimización y control de bioprocesos\biotecnología industrial