Anthony Sinskey, Ph.D.
Department of Biology
Professor of Microbiology
Sc.D. Microbiology, 1966
Massachusetts Institute of Technology
The goal of our laboratory is to establish an interdisciplinary approach to metabolic engineering, focusing on the fundamental physiology, biochemistry and molecular genetics of important organisms. We are studying the key regulatory factors in biomolecule synthesis in both prokaryotic and eukaryotic systems, including amino acid metabolism in Corynebacterium glutamicum, bioremediation and bioconversion processes in Rhodococcus, biopolymer synthesis among Gram-negative bacteria, lipid biosynthesis in oil palm, and the accumulation of secondary metabolites in tropical plants.
Our most interdisciplinary and important project right now focuses on the development of micro-bioreactors for rapid high throughput screening technologies for microbial and mammalian cells. These novel systems are equipped with on-line measurements for optical density (OD), dissolved oxygen (DO) and pH. Cultures of bacteria, yeast and eukaryotic cells have potential applications in the pharmaceutical, food, and chemical industries, and the microbioreactor platforms may enable the discovery and production of valuable therapeutics and other commercial products. This project involves a collaboration of chemical engineers, electrical engineers, surface chemists and microfabricators.
Corynebacterium glutamicum is a nonpathogenic, gram-positive, food-grade microorganism with a long fermentation history, and thus is potentially useful as a host strain for producing a number of recombinant DNA products. We have developed fundamental genetic and genomic tools that enable us to manipulate and redirect pathways involved in central carbon metabolism and amino acid production so that we can understand gene organization, structure and regulation at the molecular level. A better understanding of metabolic signal processes involved in the glucose response could have potential applications to clinical problems such as diabetes.
In the case of AIDS therapy, we are using our understanding of protein
design to predict the interactions of drugs with proteins from the HIV virus.
The virus mutates so rapidly that a single line of therapy is often evaded
immediately. With knowledge of the mechanisms of drug binding, we can design
drug candidates that bind many of the mutant proteins that might escape conventional
therapy. This approach of developing universal therapies can be applied
to other areas, such as antibiotics or antibody therapeutics.
Malaysia-MIT Biotechnology Partnership Program (MMBPP)
Along with other MIT laboratories, we are collaborating with the Palm Oil Research Institute of Malaysia on metabolic engineering to modify fatty acid synthesis in the oil palm (Elaeis guineensis). We also are collaborating with the Forest Research Institute of Malaysia to use molecular and systems biology to determine whether the complex herbal compounds that are used for natural medicines have pharmaceutical or nutraceutical value.
Economic payoff for the pharmaceutical industry
We also participate in the MIT Program on the Pharmaceutical Industry (POPI), a multidisciplinary research and educational program convened to study the process of change in the pharmaceutical industry. Our objective is to understand how technological innovations in basic sciences and systems biology can facilitate pharmaceutical drug development in personalized medicine.
- Osman, A., B. Jordan, P.A. Lessard, A.J. Sinskey, C. Rha, and D.E. Housman. 2003. Genetic diversity of Eurycoma longifolia inferred from single nucleotide polymorphisms. Plant Physiol. 131(3):1294-1301.
- Nielsen, U.B., M.H. Cardone, A.J. Sinskey, G. MacBeath, and P.K. Sorger. 2003. Profiling receptor tyrosine kinase activation using antibody microarrays. PNAS. 100(16):9330-9335.
- Glanemann, C., A. Loos, N. Gorret, L.B. Willis, X.M. O`Brien, P.A. Lessard, and A.J. Sinskey. 2003. Disparity between changes in mRNA abundance and enzyme activity in Corynebacterium glutamicum: implications for DNA microarray analysis. Appl. Microbiol Biotechnol. 61:61-68.
- Loos, A., C. Glanemann, L. Willis, X. O'Brien, P. Lessard, R. Gerstmeir, S. Guillouet, and A.J. Sinskey. 2001. Development and Validation of Corynebacterium DNA Microarrays. Appl. Environ. Microbiol. 67(5):2310-2318.
- Lessard, P.A., X.M. O'Brien, D.H. Currie, and A.J. Sinskey. 2004. pB264, a small, mobilizable, temperature sensitive plasmid from Rhodococcus. BMC Microbiol. 4(1):15-28.
- Gorret, N., S.K. bin Rosli, S.F. Oppenheim, L.B. Willis, P.A. Lessard, C. Rha, and A.J. Sinskey. 2004. Bioreactor culture of oil palm (Elaeis guineensis) and effects of nitrogen source, inoculum size, and conditioned medium on biomass production. J. Biotechnol. 108:253- 263.
- Priefert, H. X.M. OBrien, P.A. Lessard, A.F. Dexter, E.E. Choi, S. Tomic, G. Nagpal, J.J. Cho, M. Agosto, L. Yang, S.L. Treadway, L. Tamashiro, M. Wallace, and A.J. Sinskey. 2004. Indene bioconversion by a tolueneinducible dioxygenase of Rhodococcus sp.I24. Appl. Microbiol. Biotechnol. 65(2):168-76.
- York, G.M., J. Lupberger, J. Tian, A. Lawrence, J. Stubbe, and A.J. Sinskey. 2003. Ralstonia eutropha H16 Encodes Two and Possibly Three Intracellular Poly[D-(-)-3-hydroxybutyrate] (PHB) Depolymerase Genes. J. Bacteriol. 185(13):3788-3794.
Last Updated: April 16, 2008