Cells containing multiple nuclei (syncytial cells) are common across the entire tree of life and are found in every biosphere from bone, muscle, placenta and embryos of animals to the complex networks formed by fungi, water- and slime-molds. Yet little is known about the advantages an organism receives from having multinucleated cells, or how multiple nuclei communicate and coordinate to control cell behavior. This project will use biological and mathematical tools to test whether and how nuclei within multinucleate cells of the filamentous fungus Neurospora crassa adopt different roles in response to changes in the fungus' environment - allowing for a flexible division of labor within the cell. In addition to revealing general rules for nuclear coordination, the project has potential to enhance fungal productivity for food production and biotechnology. The project will offer graduate and undergraduate students interdisciplinary training in mathematical modeling, cell biology, genetics and novel microscopic imaging technology. In addition, new K-12 outreach activities will be catalyzed, including training of teachers and creation of new lesson plans on real world applications of mathematics and the utility of quantitative analysis in biology. Finally, the syncytial cell research community will be stimulated by a workshop that brings together mathematicians and scientists studying multinucleate cells in diverse organisms, including fungi.
Multinucleate cells allow the proportion of nuclei that contribute to any specific function to be dynamically tuned according to cellular requirements. But such division of labor is impossible if nuclei that share cytoplasm also see identical proteins and environmental cues. So, for nuclei to behave autonomously, protoplasm must be organized to control communication between adjacent nuclei. This project will use computational imaging, genetics and mathematical modeling to study how nuclei form communities within multinucleate cells and to dissect cellular processes that control these emergent communities. The focus will be on digestion of complex carbohydrates by Neurospora crassa to: 1) analyze the adaptive costs/benefits of nuclear coordination and division of labor; 2) determine the length scales of nuclear cooperation and autonomous behaviors; and 3) develop a linked mathematical model for inter-nuclear communication and coordination, focused on identifying general mechanisms that enable nuclear communities to stably emerge from interactions of relatively few macromolecules whose abundances are dominated by Poisson noise. The project will help discover new rules of life for how coordinated behaviors emerge from autonomous nuclei in filamentous fungi, and in syncytial cells generally, within cellular compartments that range from microns to meters in size.
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.
