Heriberto D. Cerutti
Professor - School of Biological Sciences
(402) 472-0247 | Email |
- Ph.D. Cornell University 1992
The long-term goal of our research projects is to understand the molecular basis of gene expression in eukaryotes. Gene activity is influenced by the proteins that package the DNA, by enzymes that modify these proteins or the DNA itself, and by RNA-mediated mechanisms (e.g., RNA interference). All these pathways play important roles in the control of gene expression during organismal development as well as in host defense responses against viruses and transposable elements. Thus, elucidation of these mechanisms will have an impact not only in basic biology but also in medicine and agriculture. We are currently using the unicellular green alga Chlamydomonas reinhardtii and the higher plant Arabidopsis thaliana as model systems to identify and characterize molecular components of the gene silencing machineries. We are also interested in engineering algal strains for the production of biofuels and biomaterials.
RNA Interference (RNAi)
Double-stranded RNA is the trigger at the heart of RNAi and it can induce, in different organisms, a variety of outcomes such as the degradation of homologous RNAs, transcriptional silencing, DNA methylation or even DNA elimination. The RNAi machinery has also been implicated in the processing and function of microRNAs, endogenous small RNAs that regulate gene expression by translational repression or mRNA cleavage. Despite rapid progress in understanding key steps of these pathways, many factors required for RNAi and related mechanisms have not been characterized as yet. We are using a variety of genetic, functional genomics and bioinformatics approaches to identify novel components of the RNAi machinery as well as to examine the role of these pathways in developmental programs and in the biological responses to abiotic stresses.
Algae for Biofuels
Algae have important roles in marine, freshwater and terrestrial ecosystems. For instance, 30 to 50% of the planetary net photosynthetic productivity (the difference between photoautotrophic photosynthesis and respiration) is of marine origin and dependent on phytoplankton biomass. Recently, the great potential of algae as feedstocks for renewable biofuel production has also gained recognition. Microalgae are unicellular organisms capable of harnessing sunlight and carbon dioxide to produce high-value chemical compounds, such as lipids and carbohydrates, which can be converted into fuels. Various stress conditions, such as nitrogen deficiency, trigger the accumulation of non-polar lipids (mainly triacylglycerols) in many algal species. Chlamydomonas reinhardtii is one of the best-studied eukaryotic microalgae, with a sequenced nuclear genome, extensive physiological data and a growing toolkit of genetic, genomics and bioinformatics resources. Our objective is to understand the gene regulatory networks that control metabolic pathways of lipid accumulation in Chlamydomonas, with the ultimate goal of engineering algal strains with improved capabilities for renewable biofuel production.
Cerutti H., Ma X., Msanne J. and Repas T. 2011. RNA-Mediated Silencing in Algae: Biological Roles and Tools for the Analysis of Gene Function. Eukaryotic Cell, 10: 1164-1172.
Cerutti H. and Ibrahim F. 2011. Turnover of mature miRNAs and siRNAs in plants and algae. Adv. Exp. Med. Biol. 700: 124-139.
Shaver S. S., Casas-Mollano J. A., Cerny R. L. and Cerutti H. 2010. Origin of the Polycomb Repressive Complex 2 and gene silencing by an E(z) homolog in the unicellular alga Chlamydomonas. Epigenetics, 5: 301-312.
Ibrahim F., Rymarquis L. A., Kim E.-J., Becker J., Balassa E., Green P. J. and Cerutti H. 2010. Uridylation of mature miRNAs and siRNAs by the MUT68 nucleotidyltransferase promotes their degradation in Chlamydomonas. Proc. Natl. Acad. Sci. USA, 107: 3906-3911.
Kim E.-J. and Cerutti H. 2009. Targeted gene silencing by RNA interference in Chlamydomonas. Methods Cell Biol, 93: 99-110.
Cerutti H. and Casas-Mollano J. A. 2009. Histone H3 phosphorylation: universal code or lineage specific dialects? Epigenetics 4: 71-75.
Casas-Mollano J. A., Jeong B.-r., Xu J., Moriyama H. and Cerutti H. 2008. The MUT9p kinase phosphorylates histone H3 threonine 3 and is necessary for heritable epigenetic silencing in Chlamydomonas. Proc. Natl. Acad. Sci. USA 105: 6486-6491.
Casas-Mollano J. A., Rohr J., Kim E.-J., Balassa E., van Dijk K. and Cerutti H. 2008. Diversification of the core RNAi machinery in Chlamydomonas reinhardtii and the role of DCL1 in transposon silencing. Genetics 179: 69-81.
Merchant S.S., Prochnik S.E., Vallon O., Harris E.H., Karpowicz S.J. et al. 2007. The Chlamydomonas genome reveals the evolution of key animal and plant functions. Science 318: 245-250.
Casas-Mollano J. A., van Dijk K., Eisenhart J. and Cerutti H. 2007. SET3p monomethylates histone H3 on lysine 9 and is required for the silencing of tandemly repeated transgenes in Chlamydomonas. Nucleic Acids Research 35: 939-950.
Ibrahim F., Rohr J., Jeong W.-J., Hesson J. and Cerutti H. 2006. Untemplated oligoadenylation promotes degradation of RISC-cleaved transcripts. Science, 314: 1893.
Cerutti H. and Casas-Mollano A. 2006. On the Origin and Functions of RNA-Mediated Silencing: From Protists to Man. Curr Genet 50: 81-99.
van Dijk K.V., Xu H. and Cerutti H. 2006. Epigenetic silencing of transposons in the green alga Chlamydomonas reinhardtii. Nucleic Acids and Molecular Biology 17: 159-178.
van Dijk K.V., Marley K.E., Jeong B.-r., Xu J., Hesson J., Cerny R.L., Waterborg J.H. and Cerutti H. 2005. Monomethyl histone H3 lysine 4 as an epigenetic mark for silenced euchromatin in Chlamydomonas.Plant Cell, 17: 2439-2453.
Sarkar N., Lemaire S., Wu-Scharf D., Issakidis-Bourguet E., and Cerutti H. 2005. Functional Specialization of Chlamydomonas Cytosolic Thioredoxin h1 in the Response to Alkylation-Induced DNA Damage. Eukaryotic Cell 4: 262-273.
Rohr J., Sarkar N., Balenger S., Jeong B.-r. and Cerutti H. 2004. Tandem inverted repeat system for selection of effective transgenic RNAi strains in Chlamydomonas. Plant J. 40: 611-621.
van Dijk K.V. and Cerutti H. 2004. RNA-mediated silencing. In Encyclopedia of Plant and Crop Science; Robert M. Goodman, ed.; Marcel Dekker: New York; pp. 1242-1244.
Cerutti H. 2003. RNA interference: traveling in the cell and gaining functions? Trends Genet. 19, 39-46.
Zhang C., Wu-Scharf D., Jeong B.-r. and Cerutti H. 2002. A WD40-repeat containing protein, similar to a fungal co-repressor, is required for transcriptional gene silencing in Chlamydomonas. Plant J. 31: 25-36.
Jeong B.-r., Wu-Scharf D., Zhang C. and Cerutti H. 2002. Suppressors of transcriptional transgenic silencing in Chlamydomonas are sensitive to DNA-damaging agents and reactivate transposable elements. Proc. Natl. Acad. Sci. USA 99: 1076-1081.
Wu-Scharf D., Jeong B.-r., Zhang C. and Cerutti H. 2000. Transgene and transposon silencing in Chlamydomonas reinhardtii by a DEAH-box RNA helicase. Science 290: 1159-1162.