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Stephen Mayfield

Research

Engineering algae for the production of therapeutic proteins and biofuels

The research in the Mayfield lab focuses on molecular genetics in green algae, and on the production of therapeutic proteins and biofuel molecules using algae as a production platform. To develop algae as a biotechnology platform, we are developing the molecular tools that will be used to produce either recombinant proteins or engineered biofuel molecules. We have developed a number of expression vectors that allow for robust accumulation of complex mammalian proteins including monoclonal antibodies, mammalian growth factors, and a variety of potential industrial enzymes. We have shown that this algal-based system is capable of producing these recombinant proteins at very high levels. Recent studies have focused on producing antibody-toxin fusion proteins, in which a targeting antibody domain is linked to a cell-killing toxin. Using this technology, we have produced an antibody-toxin fusion that binds and kills human B-cell lymphomas, and cell-based assays have demonstrated the utility and specificity of this molecule. These proteins have great potential for the treatment of cancers and infectious diseases, and chloroplasts offer perhaps the only system in which these types of proteins can be produced. We have also recently succeeded in generating expression vectors that allow for expression of recombinant proteins from the nuclear genome at relatively high levels, and that also allow for secretion of these proteins from the cell. These new vectors will increase the repertoire of recombinant proteins that can be produced in algae thereby expanding the platform. Engineering algae for the production of hydrocarbon molecules that can be used as biofuels is also a major focus of the lab, and recent studies have demonstrated the tremendous potential of eukaryotic algae for the expression of recombinant enzymes that allow for greater production of biofuels. Our continued genetic, biochemical and structural studies should lead to a greater understanding of the mechanism of gene expression in algae, and allow algae to become a viable source for sustainable biofuel and recombinant protein production.

Publications

Full listing of publications

  • Barrera, D. J., Mayfield, S. P. (2013) High-value Recombinant Protein Production in Microalgae. Handb. Microalgal Cult. (Emeritus, A. R. P. D. & Ph.D, Q. H.) 532–544 (John Wiley & Sons, Ltd.).
  • Gimpel, J.A., Mayfield S.P. (2013) Analysis of heterologous regulatory and coding regions in algal chloroplasts. Applied microbiology and biotechnology. 97:4499-4510.
  • Gimpel JA, Specht EA, Georgianna DR, Mayfield SP. (2013) Advances in microalgae engineering and synthetic biology applications for biofuel production. Current Opinion in Chemical Biology, 17:489–495.
  • Specht EA, Mayfield SP. (2013) Synthetic oligonucleotide libraries reveal novel regulatory elements in Chlamydomonas chloroplast mRNAs. American Chemical Society Synthetic Biology, 2(1): 34-46.
  • Rasala BA, Barrera DJ, Ng J, Plucinak TM, Rosenberg JN, Weeks DP, Oyler GA, Peterson TC, Haerizadeh F, Mayfield SP. (2013) Expanding the spectral palette of fluorescent proteins for the green microalga Chlamydomonas reinhardtii. The Plant Journal, 74(4):545-56.
  • Rasala BA, Gimpel J, Tran M, Hannon MJ, Miyake-Stone SJ, Specht EA, Mayfield SP. (2013) Genetic engineering to improve algal biofuels production. In Algae for Biofuels and Energy (Michael A. Borowitzka, ed), Springer, New York, pp. 99-114.
  • Tran M, Henry RE, Siefker D, Van C, Newkirk G, Kim J, Bui J, Mayfield SP. (2013) Production of anti-cancer immunotoxins in algae: ribosome inactivating proteins as fusion partners. Biotechnology and bioengineering, 110(11):2826-2835.
  • Tran, M., Van, C., Barrera, D.J., Pettersson, P.L., Peinado, C.D., Bui, J., Mayfield, S.P. (2013) Production of unique immunotoxin cancer therapeutics in algal chloroplasts. Proc. Natl. Acad. Sci. U. S. A. 110, E15–22.
  • Vinyard, D.J., J. Gimpel, G.M. Ananyev, M.A. Cornejo, S.S. Golden, S.P. Mayfield, & G.C. Dismukes. (2013) Natural variants of Photosystem II subunit D1 tune photochemical fitness to solar intensity. Journal of Biological Chemistry. 288:5451-5462.
  • Blatti, J. L., Beld, J., Behnke, C. A., Mendez, M., Mayfield, S. P., & Burkart, M. D. (2012). Manipulating Fatty Acid Biosynthesis in Microalgae for Biofuel through Protein-Protein Interactions. PLOS ONE, 7(9), e42949.

Biography

Stephen Mayfield obtained bachelor of science degrees in Biochemistry and in Plant Biology from California Polytechnic University in San Luis Obispo in 1979, and a Ph.D. in Molecular Genetics from the University of California at Berkeley in 1984. From 1984 to 1987 Steve was an NIH post-doctoral fellow at the University of Geneva, Switzerland. In 1987 he joined the Scripps Research Institute and become a professor and associate dean of the graduate school before leaving to join UCSD in 2009.