NSF Award
1747917
Liver disease affects millions of individuals each year. Treatment for liver disease often requires a liver transplant due to the inability of damaged liver tissue to regenerate in many cases. A better understanding how liver tissue is renewed and repaired will improve the ability to develop future interventions. Understanding tissue physiology is often complicated by the fact that cells next to each other do not necessarily respond the same manner. Emerging technologies and analysis methods aimed at high-throughput molecular assays of hundreds-to-thousands of single cells have enabled an unprecedented view of the heterogeneity, hierarchy and complexity of cellular functional states. Multiscale modeling is one tool that can aid in understanding the variation in observable cellular behavior, so this research project is developing a novel multiscale modeling framework that takes advantage of the in-depth information on cellular function that can be obtained from these single cell data sets. This modeling framework bridges from the molecular scale to the tissue scale to enhance knowledge gained about physiology and pathophysiology. While the outputs from this model will support improved understanding and manipulation of tissue response to injury in the liver, it will likely be applicable to understanding other tissues as well. The research team is integrating students of all levels, from high school through graduate school, in this project in order to excite them about scientific research and to provide them with professional development opportunities. <br/><br/>The central innovative idea of this project is to realize the full potential of the novel single cell data sets by developing models of cellular functional states and state transitions to bridge the molecular and tissue scales. The team is developing the proposed multiscale modeling framework in the context of understanding the control principles governing the coordinated tissue response to injury. This approach involves explicit accounting of cellular functional states of immune, stromal, endothelial and epithelial cells, and putative molecular processes driving the state transitions, with broad applicability to multiple tissue repair scenarios. The team is focusing on the process of liver regeneration as an enabling testbed in order to fully develop, fine tune and illustrate the multiscale modeling approach for broader application and utility.
