Transport Effects on Cellular Processes
Transport processes occur in almost every biological process ranging from the cellular to tissue to whole body level. Blood flow and fluid mechanical forces can modulate intracellular metabolism, transport enzymes and metabolites to the tissue/cell. In addition, flow can regulate signal transduction and gene expression. The objective of this project is to investigate transport processes and their effect on both the molecular and macroscopic level.
This is the study of biology as an integrated system of genetic, protein, metabolite, cellular, and pathway events that are continually changing and inter-related. Gene expression data provide information on pathways relevant to the metabolic models. Although genes yield informative clues to diseases, they do not contain functional information. Disease mechanisms can stem from genetic and environmental causes. The importance of studying biology as a system rather than one gene or protein at a time has become increasingly relevant with the advent of high throughput genomic and proteomic technologies. A systems approach can help explain why some genes respond to a particular environmental stimulus, while others do not.
In this project, metabolic engineering will be applied to further our mechanistic understanding of diseases, such as Type II diabetes, Parkinson's and Alzheimer diseases. The objective of this project is to quantify the pathway alterations in response to environmental mediators. Knowledge of in-vivo flux distributions in cells at different physiological states is of increasing importance by providing "cellular" targets for evaluation as predictors of the disease.
Micro-patterning technology allows design of cellular co-culture systems and manipulation of the cellular microenvironment to reflect in vitro the metabolism in vivo. Nonparenchymal cells can aid parenchymal cells to maintain functions, but they can also mediate deleterious effects. An advantage of this technique, upon which we will capitalize, is the ability to control the cell seeding density and the spatial orientation and placement of different cell types. Micro patterning permits engineering of cell-cell architecture and cell-cell interactions of nonparenchymal and parenchymal cells to better reflect metabolism in vivo.