Joseph Shiloach, Ph.D.
The Biotechnology Core Laboratory specializes in the large-scale production and purification of biological materials from various sources to advance research in fields such as vaccine development, structural biology, and drug production. To achieve this goal, the lab integrates two main functions: (1) production and (2) research and process development. The production is done in a multipurpose, state-of-the-art pilot production facility that serves the needs of researchers from across NIH intramural research program, and the research and development is conducted by performing independent biotechnology research. The lab is unique in its ability to successfully solve a variety of production problems, including growing large amounts of pathogenic microorganisms, obtaining proteins from mammalian cells, and performing efficient purification processes of proteins from large amounts of biomass. These methodologies are achieved by utilizing physiological, molecular biology, and technical approaches to each issue.
The lab obtains the required biological products from prokaryotic and eukaryotic microorganisms (native or recombinant), mammalian cells and tissues, insect cells, and plant tissues. Obtaining such materials in the necessary quantities is a field unto itself, one that requires the integration of biochemistry, microbiology, molecular biology, and engineering, as well as the operation and maintenance of special production instrumentation. Examples of current production items are: (1) bacteria such as Escherichia coli, Shigella, Neisseria meningitidis, Bacillus anthracis, and Halobacteria; (2) prokaryotes such as insect cells, mammalian cells (CHO, MDCK, and HEK 293), yeast, and filamentous fungi; and (3) proteins such as recombinant exotoxin A of Pseudomonas aeruginosa, modified protective antigen of B. anthracis, and the repeating unit of the A and the B subunit of the Clostridium difficile toxin.
To support these efforts, the lab conducts research studies on topics such as achieving high-density cell concentration, increasing bacterial growth, and improving the processes used to develop specific products. Long-term research efforts focus on: (1) modifying adhesion properties of mammalian cells, critical for influenza virus production; (2) investigating the central carbon metabolism of E. coli strains, used for recombinant protein production; and (3) analyzing the role of small RNA and micro RNA in regulating the growth behavior of E. coli and CHO cells.
