Chemical & Bioliological Engineering
Purity and purification costs are becoming important issues in biotechnology as the industry matures and competitive products reach the marketplace. The primary objective of Dr. Haynes’ research is to develop new natural and recombinant-protein purification processes based on high-affinity interactions between target proteins or drugs and separation media. Fundamental research focuses on development of new instrumentation, particularly microcalorimetry and UV-resonance Raman spectroscopy, for quantifying the delicate energetics of biological interactions and binding. When engineered properly, molecular genetics techniques provide a robust method for purifying recombinant proteins from the complex aqueous solutions in which they are produced. Dr. Haynes, in collaboration with Drs. Kilburn and Warren of the Microbiology department, is interested in purification strategies which use the cellulose binding domains (CBD’s) of Cellulomonas fimi cellulases as affinity tags. Genetic or chemical linkage of a CBD to the target protein creates a fusion protein which binds strongly to cellulose and retains the biological activity of the fusion partner. Recovery of the target protein is then achieved through either a modest change in system variables or enzymatic cleavage of the polypeptide backbone at the protein/CBD linkage. Many protein purification processes rely on controlled and/or well characterized adsorption at solid-liquid or liquid-liquid interfaces. For instance, chromatographic separations, such as hydrophobic, displacement and ion-exchange chromatographies, are based on differences in binding affinities of proteins for the support material. Understanding protein adsorption at synthetic surfaces is also critical to the development of improved biomaterials for use in artificial organs, vascular grafts, haemodialysis cartridges, blood bags, etc. A second interest of Dr. Haynes concerns thermodynamic (including electrostatic) aspects of protein adsorption with the aim of revealing general principles and resolving the dominant forces governing adsorption processes. Synthesis of pharmaceutical drugs often requires precursors of specified chirality. However, chemical syntheses of drug precursors, such as amino acids, typically yield racemic mixtures. Dr. Haynes is involved in the development of large-scale, continuous processes for separating mixtures of chiral enantiomers. Research to date has involved the fabrication and characterization of ligands which selectively separate chiral therapeutics with a single hydrophilic chiral center. Research in Dr. Haynes’ laboratories involves collaborations with engineers, pathologists, chemists, and microbiologists. This collaborative research environment mirrors the multidisciplinary nature of industrial biotechnology and provides a sound foundation for understanding the complex structures and functions of proteins and thus, promising pathways for their purification.