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Principal Investigator: ROBERTO DOMINGUEZ
Organization: UNIVERSITY OF PENNSYLVANIA
Fiscal Year: 2024
Award: $1,569,580
Funding agency: National Institute of General Medical Sciences
PROJECT SUMMARY
This RM1 proposal focuses on defining and characterizing the integrated systems that support
intracellular organelle transport and placement. Rather than just characterizing “molecules” as
biophysicists or “organelle dynamics” as cell biologists, our goal is to achieve an atomic-to-
cellular-to-in vivo level understanding of the mechanisms of organelle transport. Our
collaborative and multi-disciplinary research team will discover and study the native
microenvironments in cells and in vitro, by considering physiologically-relevant combinations of
molecular motors, filaments, adaptors, membranes and other cofactors that control organelle
movement and polarization. We will use mitochondria as our initial model system, as many key
molecules and signaling pathways that are essential for the dynamics of this organelle have
already been described. We will uncover the roles of spatial organization and dynamic
assembly of filaments, mechanical forces, motor activity, and other regulatory elements will be
investigated. We will reconstitute complex microenvironments in vitro to determine motile and
anchoring mechanisms. We will computationally model these systems and experimentally test
models directly in cells and in vivo. Our research team will be energized and expanded by
implementing an Exploratory Pilot Studies Program to incorporate promising early-stage-
investigators into our collaborative team.
Terms: <Actin-Activated ATPase><Actins><Adhesions><Automobile Driving><Biochemistry><Biologic Models><Biological Chemistry><Biological Models><Biophysics><Cell Body><Cells><Cellular Matrix><Cellular Regulation><Cellular biology><Classification><Complement><Complement Proteins><Complex><Computational Biology><Computer Models><Computerized Models><Cytoskeletal Filaments><Cytoskeletal Gene><Cytoskeletal Proteins><Cytoskeletal System><Cytoskeleton><Degradation Pathway><Degradative Pathway><Disease><Disorder><Drosophila><Drosophila genus><Dynein><Dynein ATPase><Dynein Adenosine Triphosphatase><Dynein Adenosinetriphosphatase><Endosomes><Filament><Goals><In Vitro><Interdisciplinary Research><Interdisciplinary Study><Investigators><Kinesin><Kinetics><Locomotor Activity><Mechanics><Membrane><Micro-tubule><Microtubules><Mitochondria><Model System><Modeling><Molecular><Molecular Motors><Motility><Motor><Motor Activity><Multidisciplinary Collaboration><Multidisciplinary Research><Myosin ATPase><Myosin Adenosine Triphosphatase><Myosin Adenosinetriphosphatase><Myosins><Organelles><Organism><Physiologic><Physiological><Physiology><Pilot Projects><Position><Positioning Attribute><Receptosomes><Regulation><Regulatory Element><Regulatory Protein><Research><Research Personnel><Researchers><Role><Signal Pathway><Social Support System><Structure><Support System><Systematics><Testing><biophysical foundation><biophysical principles><biophysical sciences><cell biology><cell growth regulation><cofactor><complementation><computational modeling><computational models><computer based models><computer biology><computerized modeling><driving><fruit fly><genetic regulatory protein><in vivo><intracellular skeleton><job environment><living system><mechanic><mechanical><mechanical force><membrane structure><microsystems><mitochondrial><nano machine><nanomachine><organelle movement><pilot study><professional atmosphere><programs><reconstitute><reconstitution><regulatory gene product><single molecule><social role><structural biology><work atmosphere><work environment><workplace climate><workplace environment>