Molecular and systems biotechnology has emerged as an important part of the current biotechnology industry. In this class, we will cover the basic concepts and techniques essential to understanding more sophisticated methods and to developing novel approaches in molecular biotechnology. In addition, methods to model and analyze biological complexity will be introduced.
The first half of the course will cover the application of techniques from molecular biology to biotechnological problems. We will emphasize the methods of protein engineering, such as rational protein design, evolutionary protein design (directed evolution) and their combination. Molecular biology techniques used in these methods will be highlighted, such as site-directed mutagenesis, random mutagenesis, saturation mutagenesis, DNA and family shuffling, homology-independent DNA recombination, phage display, cell surface display (bacterial and yeast), ribosomal display and mRNA display. We will illustrate the design of genetic selection and screen in bacteria and yeast with details. Other topics we will cover include: incorporation of unnatural amino acids into protein, yeast hydride system, riboswitches, DNA-templated organic synthesis, polyketide biosynthesis and engineering, cell surface engineering and the design of genetic circuits. Although a background in molecular biology will be useful, essential concepts will be reviewed such that the course is self-contained.
The second half of the course will focus on systems approaches for the analysis of biological complexity. We will start by covering the basic tools of metabolic engineering including metabolic flux and metabolic control analysis. The yeast amino acid biosynthesis network will be used to illustrate application of these techniques. We will emphasize the dynamic modeling of gene regulatory, signal transduction and metabolic networks. The modeling and analysis tools will be illustrated using several examples including yeast cell cycle kinetics, the eukaryotic mitogen-activated protein kinase (MAPK) signaling pathway and yeast central carbon metabolism. Although some background in linear algebra and nonlinear ordinary differential equations will be assumed, essential concepts will be reviewed to make the course as self-contained as possible.
Note: This class is open to graduate students only. Senior undergraduate students who would like to take this class must consult with the instructors in advance. Each student must complete a term project with a molecular biology or systems biology focus.