Project Grant 2204238

NSF-ANR: COLLABORATIVE RESEARCH: A MECHANICAL ATLAS FOR EMBRYOGENESIS AT SINGLE-CELL RESOLUTION -THE SCIENTIFIC GOAL OF THIS PROJECT IS TO DEEPEN THE UNDERSTANDING OF HOW LIVING MATTER GENERATES AND CONTROLS MECHANICAL FORCES TO SHAPE TISSUES, ORGANS, AND ORGANISMS. THE CENTRAL TECHNOLOGICAL INNOVATION THAT MOTIVATES AND GUIDES THE PROPOSED WORK IS THE CONSTRUCTION OF A MECHANICAL ATLAS, DESCRIBING THE MEASUREMENT OF MECHANICAL STRESSES, IN THREE DIMENSIONS, AT SINGLE-CELL RESOLUTION AND OVER TIME, IN A LIVING EMBRYO AS IT SCULPTS ITSELF. THE INVESTIGATORS WILL THEN BUILD ON THIS EFFORT TO DETERMINE THE MOLECULAR UNDERPINNINGS OF THE OBSERVED PATTERNS OF STRESS, AND DISCOVER RULES BY WHICH THESE STRESSORS COLLECTIVELY ENSURE UNIQUE MORPHOGENETIC OUTCOMES IN WAYS THAT ARE ROBUST WITH RESPECT TO PHENOTYPIC AND ENVIRONMENTAL VARIATIONS. THEY EXPECT THIS WORK WILL REVEAL NEW MECHANICAL DESIGN PRINCIPLES FOR EMBRYONIC DEVELOPMENT, WITH DIRECT IMPACT ON THE FIELDS OF TISSUE ENGINEERING AND ORGAN REGENERATION. THE METHODOLOGY AND TOOLS THAT WILL BE DEVELOPED WILL BE SHARED AS OPEN SOURCE THROUGH GITHUB; SEGMENTED EMBRYOS AND THE MECHANICAL ATLAS WILL BE MADE AVAILABLE TO THE COMMUNITY THROUGH THE MORPHONET BROWSER. THE TEAM OF INVESTIGATORS PROPOSE TO CONSTRUCT A SINGLE-CELL MECHANICAL ATLAS, IN 3D AND IN PHYSICAL UNITS, DURING THE PROCESS OF GASTRULATION IN THE ASCIDIAN EMBRYO. TO DO SO, THEY WILL SOLVE AN INVERSE PROBLEM, GROUNDED IN A NEW PHYSICAL THEORY OF MULTICELLULAR AGGREGATES, ADVANCED LIGHT-SHEET BASED IMAGING, AND BIOPHYSICAL MEASUREMENTS OF MATERIAL PARAMETERS. THEY WILL USE THIS MECHANICAL ATLAS AS A FOUNDATION TO EXPLORE HOW DYNAMIC CONTROL OF FORCE GENERATION BY ACTOMYOSIN, AND DYNAMIC COUPLING BETWEEN NEIGHBORING CELLS, ENCODES ROBUST STEREOTYPED MORPHOGENETIC TRAJECTORIES. IN PARTICULAR, THE INVESTIGATORS WILL SEEK TO DETERMINE 1) COMMUNICATION CHANNELS BETWEEN CELLS THAT CONTRIBUTE TO THE GENERATING THE PATTERNS OF MECHANICAL FORCES, 2) THE MOLECULAR GENERATOR(S) OF STRESS, 3) THE ROLES THAT MECHANICAL FORCES PLAY IN ALTERING HOW CELLS COMMUNICATE, AND 4) HOW THE OBSERVED PATTERNS OF MECHANICAL STRESS SCULPT THE MACROSCOPIC SHAPE OF THE ORGANISM. THIS MULTIFACETED RESEARCH IS MADE POSSIBLE THROUGH A HIGHLY INTERDISCIPLINARY COLLABORATION BETWEEN 4 SCIENTISTS WITH DISTINCT AND SYNERGISTIC EXPERTISE IN DEVELOPMENTAL BIOLOGY, PHYSICS, APPLIED MATHEMATICS AND COMPUTER SCIENCE. THIS COLLABORATIVE US/FRANCE PROJECT IS SUPPORTED BY THE US NATIONAL SCIENCE FOUNDATION AND THE FRENCH AGENCE NATIONALE DE LA RECHERCHE, WHERE NSF FUNDS THE US INVESTIGATOR AND ANR FUNDS THE PARTNERS IN FRANCE. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.