CAREER: Molecular Systems Bioengineering

Rutgers University New Brunswick, New Brunswick NJ

Investigators

Abstract

The overall objective of the proposed research is to develop tools of Molecular Systems Bioengineering (MSB) and apply them to understand and control gene regulatory events involved in hepatocyte (primary liver cell) differentiation. In the first stage of the project, individual binding sites on the albumin gene promoter will be assessed for liver-enriched transcription factor binding affinity and their ability to effect transcription of the albumin gene. In particular, context-dependent effects such as cooperativity and competition among binding sites will be evaluated quantitatively. Second, a molecular systems model will be developed to describe the gene network of regulatory interactions among liver-enriched transcription factor genes and corresponding proteins. Information on cooperativity and competition will be obtained from the experiments in the first stage, and the effect of genetic perturbations will be simulated. In the third stage, perturbations predicted to be fruitful will be effected using antisense oligonucleotides. Genes predicted to be most inhibitory to albumin transcription will be inhibited and the effects evaluated at the level of the gene target, albumin production and complementary hepatocyte differentiated functions. Concurrently, initiatives will be undertaken to create an educational path in Molecular Systems Bioengineering at Rutgers University. An undergraduate track in MSB will be developed in the Department of Biomedical Engineering, and interactive tutorials will be developed in the undergraduate core classes, which will be refined for use as translational materials in introducing high school student and Rutgers freshmen to opportunities in MSB.