Brief Description: This course provides an integration of engineering and mathematical principles with molecular and cell biology entities for the understanding of physiology and solution of medical problems.

Instructor: Professor Charles M. Roth
Office: Engineering C-228
Phone: 445-4109
Email: cmroth@rci.rutgers.edu
Office hours: TBA

Prerequisites: Some background in biochemistry, molecular biology, thermodynamics and kinetics. Students concerned about their preparation should contact the instructor for guidance.

Course Outline:

Lecture	Topic
0. Overview
1	Introduction. What is Molecular and Cellular Bioengineering? Technologies and applications. Engineering principles. Importance of Biointerfaces. Case study.
I. Genomics
2	Organization of the genome. Genomes, chromosomes, genes, promoters. Basics of databases and bioinformatics tools.
3	Genetic sequencing and diagnostics. Dideoxy sequencing; sequencing by micro-CE; shotgun sequencing and reassembly; Probabilistic models. Genetic markers of disease. Technologies for identifying SNPs.
4	Gene expression measurements. Real-time PCR; DNA microarrays. Effect of sequence, substrate and environment on hybridization. Data analysis.
5	Principles of genetic engineering. Recombinant DNA technology. Cloning. Reporter genes. Gene and oligonucleotide delivery.
6	Applications of genetic engineering and gene-based therapeutics. Cancer gene and antisense therapies. Agriculture. Growth factor release from scaffolds.
II. Proteomics
7	Structure and function of proteins. Primary, secondary and tertiary structure. Influence of environment on activity.
8	Protein molecular recognition. Biophysics of protein-protein interfaces. Molecular evolution techniques. Principles and examples of biosensors.
9	Proteins at surfaces – adsorption and biocompatibility. Mechanisms of adsorption. Thermodynamics and kinetics. Properties of biocompatible materials. Assessment of biocompatibility.
10	Serum protein diagnostics. Serum proteins as disease markers. Separation and analysis methods (2DE, MS). Disease fingerprinting.
11	Applications of proteins at interfaces. Biosensors. Protein chips. Micro-patterned cell cultures.
III. Molecular Systems in Cells
12	Ligand-receptor trafficking. Quantitative analysis of binding, internalization and trafficking. Maximal rates for targeted drug delivery.
13	Signal transduction. Biological principles of signaling. Topology of signaling networks. Regulation mechanisms. Experimental profiling of signal transduction, including in situ profiling.
14	Gene networks. Mathematical analysis of gene networks. Design of regulatable promoters. Artificial gene networks.
15	Metabolic cycles. Metabolic flux analysis. Metabolic control analysis. Experimental metabolite profiling. Use in optimizing cell cultures. Applications to understanding and treating disease.
16	Targeted drug delivery. Case study. Maintaining targeting functionalities in an engineered vehicle.
IV. Cellular Phenotypes
17	Proliferation. Cell cycle analysis. Quantifying cellular proliferation. Relevance to wound healing, tumor growth and in vitro cell and tissue cultures.
18	Motility. Cellular mechanisms. Random vs. directed motions. Experimental assays.
19	Apoptosis. Molecular pathways. Therapeutic control. Experimental markers. Relationship to inflammation.
20	Differentiation. Lessons from development. Applications for tissue engineering. Control via growth factors and cell-substrata cues.
21	Pathway inhibitors in cancer. Case studies. Gleevec. Iressa. Cell culture, preclinical and clinical models. Potential for pharmacogenomics.
22	Stem cell bioengineering. Sources of stem cells. Culture and propagation of stem cells. Control and characterization of differentiation processes.
V. Cells at Interfaces
23	Cellular adhesion. Cell adhesion molecules. Adhesion forces and molecular cooperativity. Design and implementation of adhesion ligands on biointerfaces.
24	Biomaterial-induced inflammatory responses. Immune responses to biomaterials. Chemistry for non-immunogenic materials. In vitro assays for characterizing inflammatory responses.
25	Cell transplantation. Design requirements for cell encapsulation. Materials for encapsulation. Transport considerations. Application to diabetes.
26	Drug and gene delivery from materials. Compatibility of materials with drugs and genes. Activity upon encapsulation and release. Controlling release profiles. Examples.

Textbook: There is no textbook to adequately cover the course material. Readings – both review papers and seminal and cutting-edge original reports – will be distributed from the recent literature. It is recommended that students have one of the following texts as a reference:

Bruce Alberts et al., Molecular Biology of the Cell, 4th. ed. Garland Pub., 2002 (ISBN: 0815332181).

Or Harvey Lodish et al., Molecular Cell Biology. W.H. Freeman and Company, 1995 (ISBN: 071673706X)

Homework: Assignments will comprise a mixture of problem sets, designed to reinforce quantitative concepts; short writing assignments based on integrating principles from class with
journal papers from the current literature; and reports based on in-class laboratory demonstrations.

Course Lab: In its initial offering, the course will not have a formal laboratory period. Two to three laboratory demonstrations will be arranged during the course of the semester, the concepts from
which will be reinforced via background reading and a homework assignment.

Course Project: Students will prepare an integrative term paper that will describe: a) a relevant biomedical problem, b) fundamental biological principles, c) the role of interfacial science in the
problem or its potential solution, d) an engineering approach to its solution. In addition to integrating biological sciences, engineering and interfaces, the project should also integrate on the
molecular to cellular scale. Topics will be chosen pertaining to students’ research projects or suggested by the instructor. One week after the conclusion of each major class module
(Genomics, Proteomics, Molecular Systems, Cellular Phenotypes), an update to the class project will be submitted and assessed. Projects will be presented to the class during the final class period
in the form of a poster, and a written report will also be turned in.

Coursework and Assessment: Grades will be based on the following formula (subject to amendment):
Homework 15%
Integrative Project 30%
Lesser {Exam 1, Exam 2} 20%
Greater {Exam 1, Exam 2} 35%

Relationship of Course to Program Objectives: This is among the core courses of the IGERT Training Program on Integratively Engineered Biointerfaces. As such, there is an emphasis on
interdisciplinary and integrative approaches to the development of biomedical technologies.