The regulation of organ size during animal development depends on both internal and external inputs: internal factors include genetic makeup and external factors include applied mechanical stresses and the chemical composition of the surrounding local environment. The mechanisms by which internal and external factors regulate organ size are still not fully elucidated. A greater understanding of organ size regulation may enable researchers to better understand developmental growth in tissue and stem cell engineering constructs. Organ development in basic model systems such as the fruit fly provides valuable insight into human biology. The organ culture system will be used to test basic hypotheses of how internal and external stimuli affect organ development. The researchers will use the latest biological reporters to quantify intra-organ, cell-to-cell signaling. The technical research will be augmented by a digitized learning module illustrating principles of growth and intercellular communication based on the live-imaging data obtained from the proposed scientific study. Research impacts will be enhanced with an academic outreach program mentoring a diverse population of high school students pursuing science fair projects at local high schools near South Bend, IN.
Intercellular coordination of pattern formation, homeostasis and organ growth is a fundamental biological process during organ development. Despite this basic function, a unifying theory integrating known contributors to the mitotic cycle remains elusive. The proposed study aims to investigate the hypothesis that intercellular calcium waves encode information on the size, differentiation state and overall physiology of epithelia. To test this hypothesis, the investigators propose developing new biophysical methods to investigate intercellular calcium signaling in intact epithelial organs within a controlled microenvironment. The proposed coupling of a controlled microenvironment with live-imaging studies in a genetically modifiable model system will enable a systematic investigation into the response of developing epithelia to genetic, chemical, mechanical, and electrical perturbations. The proposed biophysical methods provide a level of experimental control and evaluation unseen in previous efforts. If successful, a quantitative understanding of the functional role of intra-organ calcium waves in developing epithelia will be a salient metric that is translatable to understanding development in high-order biological structures. A unified model of exogenous and intrinsic growth regulation will have broad implications for biomedical research; an example is the ability to direct cellular signaling in stem cell culture and tissue engineering as well as correctly scaling the features of organ-on-a-chip for basic biomedical research. Further, the REMChip will be a translatable tool that can be utilized in other model systems. A digitized learning module illustrating principles of growth and intercellular communication will be developed based on the live-imaging data obtained from the proposed scientific study. Research impacts will be enhanced with an academic outreach program mentoring a diverse population of high schools students pursuing science fair projects at local high schools.
This award is supported jointly by the Cellular Dynamics and Function Cluster in the Division of Molecular and Cellular Biosciences and by the Biotechnology, Biochemical and Biomass Engineering Program in the Division of Chemical, Bioengineering, Environmental and Transport Systems.
