Monica A. Daley - US grants

Animals move with superb agility, achieving exceptional athletic feats of endurance, speed and rapid maneuvering through complex terrain. This requires precise coordination of muscle contraction, sensing and neural control in response to rapidly changing interactions with the physical environment. Modern science has revealed increasing detail about the molecular mechanisms, growth and function of discrete tissues and systems such as muscle, neurons and bone. Yet a pronounced gap exists in understanding how these systems work together to achieve agile whole-body movement. The Integrative Movement Sciences Institute (IMSI) will bring to together 26 faculty from 21 institutions, with collective expertise across the spectrum of movement sciences from molecular biophysics of muscle to human rehabilitation and human-machine interaction. IMSI will create a nationwide collaboration network and training pipeline from undergraduate to faculty levels, to transform our field by integrating understanding of muscle function and movement from molecules to behavior. IMSI will train the next generation of scientists in effective cross-disciplinary communication, team-based science, mathematical modeling, data analysis and open data sharing. Research activities will focus on development of integrated models of movement with a wide range of applications for human exercise sciences, rehabilitation, and mobility assistance, including the design and control of prostheses, exoskeletons, and biologically-inspired legged robots.

A pronounced gap exists between ?top-down? approaches that focus on whole-animal behavior but lack insight into underlying mechanisms and ?bottom-up? approaches that identify molecular and biophysical mechanisms but lack insight into their contributions to behavior. Muscle forms a critical link in integrating mechanics and control of movement across scales. This project will fund communication, training and collaborative research development activities over 12-months to establish the Integrative Movement Sciences Institute (IMSI) at the University of California Irvine (UCI), with 26 faculty from 21 academic institutions. IMSI ?Design? activities include a workshop in Spring 2021 and a 4-week long Summer Research Institute in Summer 2021. Workshop activities will encourage thinking across disciplines and developing effective team-based collaborative approaches to overcome the challenges that currently inhibit integration across fields and organizational scales. The workshop will consolidate IMSI research themes and develop proposals for IMSI Summer Research Institute activities. The Summer Research Institute will be a 4-week event for enrolled trainees (undergraduates, graduate students and postdocs working in near-peer mentoring teams), with visiting PIs joining for one week to collaboratively lead seminars and short lab courses on topics designed to build interdisciplinary partnerships and integrate across scales. IMSI will focus on development of computationally tractable and predictive modeling tools for integrative neuromechanics of movement. These tools have potential to transform numerous fields? enabling neuroscientists, biologists, clinicians and biomedical engineers to ask questions about integrative whole organism behavior, sensorimotor control, musculoskeletal function and neuromuscular plasticity.

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.

Moving animals achieve impressive athletic feats of endurance, speed, and agility in complex environments. Animal locomotion is particularly impressive in contrast to that of human-engineered machines. The stability, agility and energy economy of current robots, prostheses and exoskeletons remains poor compared to animals. This pronounced gap between animal performance and technology stems, in part, from fundamental gaps in the understanding of muscle physiology and mechanical function. Muscle is the only actively controlled tissue in animal musculoskeletal systems, and therefore plays a central role in enabling and controlling movement. Yet, developments over the past 20 years have led to growing recognition that important problems in muscle physiology and movement sciences remain unsolved and the theoretical foundation of the field remains incomplete. In particular, the ability to model and predict muscle function under dynamic and perturbed locomotor conditions remains poor. This project will combine innovative experimental techniques with modeling approaches to develop new muscle models that can explain and predict muscle movement under a broad range of conditions. The findings have potential to transform numerous fields? enabling neuroscientists, biologists, clinicians and biomedical engineers to ask questions about human and animal behavior, control of motion, function of muscles and bones, and capacity of the nervous system and muscles to change. The research team will collaborate with colleagues in clinical and engineering fields to translate the findings into applications in human rehabilitation, treatment of disease and injury, and the design and control of assistive technology such as prosthetics and exoskeleton devices.

In the field of animal neuromechanics, a pronounced gap exists between ?top down? approaches ? those that focus on whole-animal behavior but lack insight into underlying mechanisms? vs ?bottom-up? approaches ? those that characterize mechanisms but lack insight into their contributions to animal behavior. The team will develop new tools to bridge this gap: 1) predictive muscle models that include intrinsic viscoelastic properties; and 2) experimental approaches that integrate across levels. This project?s novel ?muscle avatar? approach will help bridge this gap, and enable rigorous analysis of intrinsic muscle property and neural activation contributions to control of locomotion. Aim 1 tests the ability of the muscle avatar approach to replicate steady and perturbed in vivo work loop patterns in mouse and guinea fowl muscles. In Aim 2, in vivo muscle strain, activation, and force will be measured during steady and perturbed running in guinea fowl muscles, and the muscle avatar will be used to quantitatively assess how intrinsic muscle properties and neural drive each contribute to stabilizing responses. In Aim 3, alternative muscle models will be developed, and the ability of each model to predict in vivo muscle function in high strain and perturbed contraction conditions will be compared. Computationally tractable muscle models are essential for closed loop neuromechanical simulations of locomotion, which are increasingly used to understand how muscle function and sensorimotor control change in response to aging, injury and neuromuscular disorders. The findings could inform clinical rehabilitation strategies and the design of assistive devices.

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.

It remains a Grand Challenge in biology to understand the integrated function of living physical systems and the dynamic interactions between organisms and their environments. Understanding the physical function of organisms forms a critical link in the ?Rules of Life?? essential for integrating across scales from molecules to biospheres. However, a gap exists between ?top-down? approaches that focus on whole-organism behavior but lack insight into underlying mechanisms and ?bottom-up? approaches that characterize molecular and biophysical mechanisms but lack insight into their contributions to whole-organism behavior. We propose a 2.5-day workshop to bring together diverse scientists at the intersection of organismal biology and physics. A key focus will be integrative perspectives that enable scientists to understand how organisms robustly sense and respond to their environment. The workshop will generate important opportunities for communication and collaboration between distinct scientific fields at the interface of physics and organismal biology. The workshop will emphasize organismal function and biological diversity in an ecological and evolutionary context. A hybrid in-person and virtual format will be used to facilitate inclusive participation of underrepresented groups. The physics of living systems is a highly visual and engaging field of study that can inspire a new generation of scientists. Public online activities (YouTube live streaming, social media posts, web site) will provide opportunities for general audiences to engage with organismal biology as well as accessible resources for education and outreach.

Organisms are complex systems of interconnected elements that must achieve coordinated function and environmental responses across spatial and temporal scales. Modeling tools from mathematics, physics and engineering are becoming increasingly important for hypothesis driven research in organismal function and organism-environment interactions. Cross-disciplinary dialogue and collaboration are required to make effective use of these tools. Yet, a disconnect often exists between the use of models in the physical sciences and the effective translation and use of these models in biology. This workshop will bring together scientists at the intersection of organismal biology and physics with shared interests in using model-based approaches to address fundamental questions about organismal structure and function in comparative, ecological and evolutionary contexts. We will bring together scientists from diverse backgrounds to discuss recent innovations, challenges and community needs for transformative advances in organismal biomechanics. The workshop will use a hybrid in-person and virtual format, making use of synchronous and asynchronous online tools to facilitate communication, collaboration and dissemination of outcomes. Activities will include keynote and invited speakers, group discussions and small-group brainstorming sessions. Early career researchers including postdoctoral scientists and advanced graduate students will be recruited to act as discussion facilitators in virtual breakout sessions, providing an opportunity to develop and demonstrate communication skills and make important scientific network connections. Online elements will be used to develop an ongoing international community and collaborative research network, with sharing of open access resources to help facilitate broader public engagement with the physics of living systems.

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.