ABSTRACT

The NSF-Simons Center for Multiscale Cell Fate Research at the University of California, Irvine will provide a stimulating and empowering intellectual and physical environment for innovative team research at the interface between mathematics and biology. A cell's fate -- differentiation into a specific biological cell type -- is determined by several interlinked factors: cell-intrinsic mechanisms, signals from the local environment outside the cell, and messages the cell receives from other cells. Despite unprecedented amounts of experimental data at single-cell resolution, how cell fate is determined remains not fully understood. Challenges to development of a theory arise from information crosstalk at multiple temporal and spatial scales, as well as from the need to mine, integrate, and model the new single-cell "big data" derived from experimental measurements. To address these challenges and to establish a founding paradigm for multiscale cell fate research, a team of mathematical scientists and biologists will develop novel mathematical, computational, and statistical tools to analyze cell fate through a multiscale lens. The Center will carry out a coherent program for community building, interdisciplinary training and workforce development, and diversity enhancement to expand the mathematics-biology interface and to promote the convergence of mathematical and biological sciences. The Center will produce cohorts of interconnected young researchers and will nationally seed the next generation's laboratories. The knowledge gained will create new multiscale mathematics for analyzing big data and modeling complex systems, with broader applications to regenerative medicine, embryonic development, and birth defects.

The NSF-Simons Center for Multiscale Cell Fate Research will establish new understanding of mechanisms and principles of cell fate control through investigation of emerging behavior of cells across scales. The study aims for transformative insight into cell fate, with a focus on three biological themes: cellular complexity and plasticity in skin, stochastic dynamics and migration of neural crest cells, and epigenetic control of stem cell specification. While each theme addresses different gaps in understanding of cell fate, they all emphasize emergent complexity arising from multiscale interactions, and they share several mathematical aspects. The Center aims to develop new mathematical methods driven by these specific cell-fate questions as well as broader biological applications. Data-driven and principle-based multiscale models of cell fate will guide experiments, with subsequent feedback to the modeling efforts. Three concerted efforts will be made to enhance overall capacity of research and training at the interface between mathematics and biology: 1) expanding mathematical sciences proximal to the biology interface, 2) connecting mathematical scientists across the spectrum, and 3) fostering mathematical scientists' ability to connect directly to experiments. A wide range of new and closely interconnected community-building and outreach programs, including community-initiated Interdisciplinary Opportunity Awards, a Convergence Accelerator Team program with national reach, a BioBridge Clinic on experimental techniques, and a Mathematical Experience through Learning Research program for high school students, will be developed and implemented to achieve the Center's ambitious goals.

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.

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