Growth and size in living matter

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NON-TECHNICAL SUMMARY Living systems usually have characteristic sizes: Mice do not grow larger than elephants, and healthy bacteria generally choose to divide when they reach the appropriate length rather than to continue elongating forever. In at least some cases, these sizes appear to be specified with fairly high precision. For example, organs from human limbs to fruit fly wings exhibit size asymmetry between the left and right organ in the same animal of about 1%, and in appropriate conditions the coefficient of variation of bacterial length at division is around 10%. Very little is known about where these numbers come from. What sorts of noise or variability inside the living organism ultimately contribute the most to size errors? Is a 1% difference in wing sizes surprisingly good, close to the limits of what is possible given basic laws of physics, or would it be easy to imagine how the difference could be made even smaller? This project with use methods from the physical sciences to develop the basic theoretical framework needed to answer questions like these. The investigators will further collaborate with experimental labs to refine their ideas and apply them to specific living systems.The project will also give students at all levels an opportunity to pursue research in an interdisciplinary team; in particular, the principal investigator will work with the University of Michigan’s M-STEM Academies to recruit a diverse group of undergraduate students to the project team. The principal investigator will also develop tutorial exercises, based on his research in biological physics, for the introductory physics course sequence for life science students at the University of Michigan.TECHNICAL SUMMARYThis proposal funds theoretical and computational research, including collaborations with several experimental groups, to study the statistical and nonlinear physics of growing, active systems like those found in living matter. A unifying question is how noise and fluctuations affect growth and limit the precision with which a given final size can be reached. The investigators will explore these issues at multiple scales and in multiple model systems. In particular, they will: (1) Examine lumped, space-free models of stochastic growth and growth arrest, with applications to (A) size distributions of cells and organs; (B) size coordination between contralateral wings in the fruit fly Drosophila melanogaster; and (C) size coordination between contralateral somites during zebrafish somitogenesis. Formally, these models will initially take the form of first passage problems in two variables, an actual and an estimated size. Extensions will include allowing for the presence of various forms of correlated and non-white noise. (2) Study cell-based models of spatially resolved growth in tissues. Goals here will be to determine how correlations in cell size across tissues can be used to draw inferences about mechanisms of tissue size regulation and to understand what limits the uniformity of cell size in cohesive tissues. In particular, the investigators will compare and contrast models in which growth and proliferation arrest occur simultaneously with models where cell size adjustment and correction occurs after division has ceased. Theoretical predictions will be compared to observations in Drosophila wings and dorsal pupal notum.This project will integrate education with interdisciplinary research while supporting a diverse student body, enriching classroom instruction, and reinforcing efforts to sustain a cohesive quantitative biology community at the University of Michigan. It will give students at all levels an opportunity to pursue research in a team where they will work closely with colleagues from both the biological and the physical sciences and will support international research experiences for one graduate student. The principal investigator will work with the University of Michigan’s M-STEM Academy to involve a diverse group of undergraduates in research early in their college careers; such involvement has been shown to improve retention of students from historically under-represented groups in science and engineering fields. The project further supports the continued development of studio exercises incorporating biologically relevant examples for the introductory physics course sequence for life sciences majors and the principal investigator’s work in organizing an interdisciplinary quantitative biology seminar and journal club series at the University of Michigan.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.