Molecular genetics and biochemistry of retrotransposons and metabolic engineering in yeast
American Academy of Microbiology, Elected Fellow
American Association for the Advancement of Science, Elected Fellow
UCI College of Medicine Research Associates' Award
Damon Runyon-Walter Winchell Postdoctoral Fellow
Our laboratory studies retroviruslike elements using the budding yeast (Saccharomyces cerevisiae) retrotransposon Ty3. Retrotransposons make up almost half of the human genome but their regulation and impact on genomic function is not yet well understood; we study Ty3 as a model for understanding both retrotransposons and also retroviruses. Ty3 studies have elucidated the roles of virus structural protein in capsid assembly, roles of nucleoporins in nuclear entry and roles of transcription factors in integration specificity. We are currently focused on how RNA processing proteins help to localize and package the genomic RNA into particles. In addition, the laboratory is working to elucidate the genomic features which affect integration into chromosomal target sites. The laboratory uses a combination of molecular genetics, biochemistry and next generation sequencing to address these questions.
We are using nonconventional yeast to bioengineer metabolism to allow the biosustainable production of high-value chemicals. We developed a unique series of plasmids to allow combinatorial expression of genes for pathway engineering in Saccharomyces cerevisiae. However, S. cerevisiae is fermentative which restricts some of the metabolic studies that it supports. We therefore also study a yeast, Yarrowia lipolytica, which has aerobic metabolism more similar to that of humans than that of S. cerevisiae. Y lipolytica stores excess carbon as lipid rather than polysaccharide. We sequenced, assembled and annotated a reference genome for the industrial CLIB89 strain of this yeast. Recently we completed transposon saturation mutagenesis of this strain in order to identify essential genes and to enable screening for conditionally essential genes. This approach is generally applicable to the development of new fungal systems in order to exploit their diverse metabolism for production of important chemicals.
For more information, please see recent publications below or visit the laboratory homepage (http://http//sbspowerserver.biochem.uci.edu).
Patterson, K., Yu, J., Landberg, J., Chang, I., Shevarebi, F., Bilanchone, V., Tam, T., Sandmeyer, S. Functional genomics profiling of the industrial yeast Yarrowia lipolytica (submitted).
Magnan*, C., Yu*, J. Chang*, I., Jahn, E., Kanomata, Y., Wu, J., Zeller, M., Oakes, M., Baldi, P., Sandmeyer, S. Sequence assembly of Yarrowia lipolytica strain W29/CLIB89 shows transposable element diversity. (2016) PLOS ONE, http://dx.doi.org/10.1371/journal.pone.0162363.
Sandmeyer, S.B., Patterson, K., and Bilanchone, V.W., Ty3, a position-specific retrotransposon budding yeast. (2015) Chapter 42. Mobile DNA III, Ed. Craig, N. L., Chandler, M., Gellert, M., Lambowitz, A., Rice, P., and Sandmeyer S.B., ASM Press, Washington DC. Doi:10.1128/9781555819217. Also published in ASM Microbiology Spectrum 3 no. 2 doi:10.1128/microbiolspec.MDNA3-0057-2014.
Bilanchone, V., Clemens, K., Kaake, R. Dawson, AR, Matheos, D., Nagashima, K. Sitlani, P., Patterson, K., Chang, I., Huang, L., and Sandmeyer, S. (2015) Ty3 Retrotransposon hijacks mating yeast RNA processing bodies to infect new genomes. PLoS Genetics: 11(9): e1005528. Doi:10.1371/journal.pgen.1005528.
Qi, X., Vargas, E., Larsen, L., Hung, S-P., Lathrop, R., Hatfield, G.W., and Sandmeyer, S.B. (2013) Directed DNA shuffling of retrovirus and retrotransposon integrase protein domains PLoS ONE 8:e63957.doi:10.1371/journal.pone.0063957.
Clemens*, K., Beliakova-Bethell*, N., Bilanchone, V., Larsen, L. Z., Nguyen, K., and Sandmeyer, S. B. Different sequence requirements for Ty3 RNA association with P-body proteins and packaging. (2013) Virus Research 171, 319-331.
Qi X., and Sandmeyer S. (2013) Nonhomologous Recombination: Retrotransposons. In: Lennarz W.J. and Lane M.D. (eds.) The Encyclopedia of Biological Chemistry, vol. 3, pp. 283-291. Waltham, MA: Academic Press.
Liu, P., Chernyshov, A., Najdi, T. Fu, Y., Dickerson, J., Sandmeyer, S., Jarboe, L. (2013) Membrane Stress Caused by Octanoic acid in Saccharomyces cerevisiae Applied Microbiology and Biotechnology 97:3239-3252.
Qi, X. and Sandmeyer, S.B. In vitro targeting of strand transfer by the Ty3 retroelement integrase. (2012) J. Biol. Chem. 287, 18589-18595. PMCID 3365781
Qi*, X., Daily*, K., Nguyen*, K., Wang, H., Mayhew, D., Rigor, P., Forouzan,S., Johnston, M., Mitra, R.D., Baldi, P. and Sandmeyer, S.B. (2012) Retrotransposon profiling of RNA polymerase III initiation sites. Genome Res. 22, 681-92.
Shen, M.W.Y., Fang, F., Sandmeyer, S., Da Silva, N.A.
Development and Characterization of a Vector Set with Regulated Promoters for Systematic Metabolic Engineering of Saccharomyces cerevisiae. (2012) Yeast 29, 495-503.
Christiansen, K., Larsen, L.Z., Zhang, M., Kuznetsov, Y., Bilanchone, V., Beliakova-Bethell, N., Randall, A., DaSilva, R., Nagashima, K., McPherson, A., Baldi, P. and Sandmeyer, S.B. (2011) Ty3 spacer controls intracellular condensation and uncoating. Ty3 spacer controls intracellular condensation and uncoating. J. Virol. 2011 (Epub Jan26; PMID: 21270167; doi:10.1128/JVI.01055-10).
Zhang, M. *, Larsen, L.S.Z. * , Irwin, B., Bilanchone, V., and Sandmeyer, S.B. (2010) Ty3 Capsid subdomain interactions contribute to viruslike particle stability. Mobile DNA, 1:14.
Fang, F., Salmon, K., Shen, M., Aeling, K, Ito, E., Irwin, B., Tran, U., Hatfield, G.W., Da Silva, N.*, and Sandmeyer, S.* (2010) A combinatorial vector set for metabolic engineering in Saccharomyces cerevisiae. Yeast 28(2) 123-136 (Epub DOI: 10.1002/yea.1824).
Beliakova-Bethell, N., Terry, L.J., Bilanchone, V.W., DaSilva, R., Nagashima, K., Wente, S., and Sandmeyer, S.B. (2009) Ty3 nuclear entry is initiated by viruslike particle docking on nucleoporins. In press, J. Virol. 83: 11914-11925. Chosen for Nov Issue Spotlights.
Larsen, L.S.Z., Beliakova-Bethell, N., Bilanchone,V., Zhang, M., Lamsa, A., DaSilva, R., Hatfield, G.W., Nagashima, K., and Sandmeyer, S.B. (2008). Ty3 nucleocapsid controls localization of particle assembly. J. Virol. 82:2501-2514.
Larsen, L.S.Z., Kuznetsov, Y. McPherson , A. Hatfield, W. and Sandmeyer, S. (2007) Gag3 protein forms ordered particles in Escherichia coli. Virol. 370:223-227.
Larsen, L.S.Z., Zhang,M., Beliakova-Bethell, N., Bilanchone,V., Lamsa A., Nagashima, K., Najdi, R., Kosaka, K., Cheng, J., Baldi, P. Hatfield, G.W. and Sandmeyer, S.. (2007) Ty3 capsid mutations reveal early and late functions of the amino-terminal domain. J. Virol. 81:6957-6972.
Beliakova-Bethell, N., Beckham, C., Giddings, T.H. Jr., Winey, M., Parker, R., and Sandmeyer, S. (2006) Virus-like particles of the Ty3 retrotransposon assemble in association with P-body components. RNA 12:94-101.
Kuznetsov*, Y.G., Zhang*, M., Menees, T. McPherson, A, and Sandmeyer, S. (2005) Investigation by atomic force microscopy of the structure of Ty3 retrotransposon particles. J. Virol. 79: 8032-8045.
Irwin*, B., Aye*, M., Baldi, P., Beliakova-Bethell, N., Cheng, H., Dou, Y., Liou, W. and Sandmeyer, S.B. (2005) Retroviruses and yeast retrotransposons use overlapping sets of host genes. Gen. Res. 15:641-654.
Aye, M. Irwin, B., Archibald, H., and Sandmeyer, S.B. (2004) Host factors that affect Ty3 retrotransposition in Saccharomyces cerevisiae. Genetics 168, 1159-1176.
*Yieh, L., *Hatzis, H., Kassavetis, G., Geiduschek, E.P. Sandmeyer, S.B. (2002) Mutational analysis of the TFIIIB-DNA target of Ty3 retroelement integration. J. Biol. Chem. 277:25920-25928.
Sandmeyer, S., Aye, M., and Menees, T. (2002) Ty3: A Position-Specific, Gypsylike Element in Saccharomyces cerevisiae. In Mobile DNA, ASM Press, Washington DC.
Host Institution University of Iowa (PI Shanks)
Center for BioRenewable Chemicals,
Subcontract to Sandmeyer total:
This is an interdisciplinary project to use biosynthetic pathways in E. coli and S. cerevisiae to produce intermediates for industrial applications. The goal of the work in yeast in which the Sandmeyer laboratory is involved is to develop methods for production of short chain (<16 C) fatty acids in S. cerevisae.
1S10OD021718-01 High-Throughput Illumina 4000 DNA Sequencer (Sandmeyer, PI) 02/01/16 - 01/31/17
Genetics Society of America
American Society for Microbiology
American Society for Biochemistry and Molecular Biology
American Association for the Advancement of Science
American Academy of Microbiology
Genomics High-Throughput Facility 1999—pres
Institute for Genomics and Bioinformatics 2009—pres
Cellular and Molecular Biosciences
Mathematical and Computational Biology
Institute for Genomics and Bioinformatics
Center for Virus Research
Chao Family Comprehensive Cancer Center
Center for Biorenewable Chemicals (ISU)