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.
Tissue engineering 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. Tissue engineering permits engineering of cell-cell architecture and cell-cell interactions of nonparenchymal and parenchymal cells to better reflect metabolism in vivo.
Targeted Drug Delivery Systems
Current delivery systems bring one type of biomolecule, e.g., one protein or one gene, at a time to the targeted site. We are developing platforms to integrate polymers with biomolecules, such as aptamers, to deliver multiple biomolecules to a targeted pathway or site.