CURRICULUM VITAE Name: JINRONG PENG, PH.D Position: Principal Investigator Address: Institute of Molecular & Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673 Telephone: 65-65869729 (O) E-mail: pengjr@imcb.a-star.edu.sg Fax: 65-67791117 EDUCATION/EMPLOYMENT Date University/Institute Degree/Position Sept. 1980-July 1984 Sichuan University B.S Sept. 1984-Aug. 1987 Shanghai Institute of Biochemistry, Chinese Academy of Sciences M.S Sept. 1987-Feb. 1990 Dept of Biochemistry, Fudan University Assistant Lecturer and Researcher March 1990-Aug. 1993 Mol. Genetics Dept., Cambridge Lab., John Innes Centre, UK Ph.D Sept. 1993-Oct. 1999 Mol. Genetics Dept., Cambridge Lab., John Innes Centre, UK Higher Scientific Officer Nov. 1999-July 2002 Functional Genomics Lab Institute of Molecular Agrobiology National Univ. of Singapore Principal Investigator Aug. 2002-Aug. 2008 Institute of Molecular & Cell Biology 61 Biopolis Drive, Proteos, Singapore 138673 Principal Investigator From Sept. 2008 浙江大学动物科学学院 长江教授(全职) 1 PUBLICATIONS As corresponding or co-corresponding author: 16. Liu, Y.M., Du, L.S., Osato, M., Teo, E.H., Qian, F., Jin, H., Zhen, F.H., Xu, J., Guo, L., Huang, H.H., Chen, J., Geisler, R., Jiang, Y.J., Peng, J.R. and Wen, Z.L. (2007) The zebrafish udu gene encodes a novel nuclear factor and is essential for primitive erythroid cell development. Blood 110:99106. 15. Hussain A., Cao, D.N., Peng, J.R. (2007) Identification of conserved tyrosine residues important for gibberellin-sensitivity of Arabidopsis RGL2 protein. Planta 226:475-483. 14. Cao, D.N., Cheng, H., Wu, W., Soo, H.M., and Peng, J.R. (2006) Gibberellin mobilizes distinct DELLA-dependent transcriptomes to regulate seed germination and floral development in Arabidopsis. Plant Physiol. 142: 509–525. 13. Cheng, W., Guo, L., Zhang, Z.H., Soo, H.M., Wen, C.M., Wu, W., and Peng J.R. (2006) HNF factors form a network to regulate liver-enriched genes in zebrafish. Dev. Biol. 294: 482-496. 12. Achard, P., Cheng, H., De Grauwe, L., Decat, J., Schoutteten, H., Moritz, T., Van Der Straeten, D., Peng, J.R., Harberd, N.P. (2006) Integration of plant responses to environmentally activated phytohormonal signals. Science 311: 91-94. 11. Chen, J., Ruan, H., Ng, S.M., Gao, C., Soo, H.M., Wu, W., Zhang, Z.H., Wen, Z.L., Lane, D.P., Peng J.R. (2005) Loss-of-function of def selectively up-regulates 113p53 expression to arrest expansion growth of digestive oegans in zebrafish. Genes & Development 19: 2900-2911. 10. Cao, D.N., Hussain, A., Cheng, H., and Peng, J.R. (2005) Loss of function of four DELLA genes leads to light- and gibberellin-independent seed germination in Arabidopsis. Planta 223: 105-113. 9. Hussain, A., Cao, D.N., Cheng, H., Wen, Z.L., and Peng, J.R. (2005) Identification of conserved Ser/Thr residues important for gibberellin-sensitivity of Arabidopsis RGL2 protein. Plant Journal 44:88-99. 8. Qian, F., Zhen, F.H., Ong, C., Jin, S.W., Soo, H.M., Stainier, D.Y.R., Lin, S., Peng, J.R., and Wen, Z.L. (2005) Microarray analysis of zebrafish cloche mutant using amplified cDNA and identification of potential downstream target genes. Developmental Dynamics 233:1163-1172. 7. Wen, C.M., Zhang, Z.H., Ma, W.P., Xu, M., Wen Z.L., and Peng, J.R. (2005) Genome-wide identification of female-enriched genes in zebrafish. Developmental Dynamics 232:171-179. 6. Chen, J., Li, W.X., Xie, D.X., Peng J.R., and Ding S.W. (2004) Viral virulence protein suppresses RNAi mediated defence but upregulates the role of miRNA in host gene expression. Plant Cell 16:1302-1313. 5. Cheng, H., Qin, L.Q., Lee, S.C., Fu, X.D., Richards, D.E., Cao, D.N., Luo, D., Harberd, N.P., and Peng, J.R. (2004) Gibberellin regulates Arabidopsis floral development via suppression of DELLA protein function. Development 131:1055-1064. 4. Hussian, A. and Peng, J.R. (2003) DELLA proteins and GA signalling in Arabidopsis. J. Plant Growth Regul. 22:134-140 2 3. Lo,J., Lee, S.C., Xu, M., Liu, F., Ruan, H., Eun, A., He, Y.W., Ma, W.P., Wang, W.F., Wen, Z.L., and Peng, J.R. (2003) 15,000 Unique Zebrafish EST clusters and their future use in microarray for profiling gene expression patterns during embryogenesis. Genome Research 13:455-466. 2. Peng, J.R., and Harberd, N.P. (2002) The role of GA-mediated signalling in the control of seed germination. Current Opinion in Plant Biology 5:376-381. 1. Lee, S.C., Cheng, H., King, K.E., Wang, W.F., He Y.W., Hussian, A., Lo, J., Harberd, N.P., and Peng, J.R. (2002) Gibberellin regulates Arabidopsis seed germination via RGL2, a GAI/RGA-like gene whose expression is up-regulated following imbibition. Genes & Development 16:646-658. As first author or co-author: 26. Jin, B.L., Tao, Q., Peng J.R., Soo, H.M., Wu, W., Ying, J.M., Fields, C.R., Delmas, A.L., Liu, X.F., Qiu, J.X., and Robertson, K.D. (2008) DNA methyltransferase 3B (DNMT3B) mutations in ICF syndrome lead to altered epigenetic modifications and aberrant expression of genes regulating development, neurogenesis, and immune function. Human Molecular Genetics 17: 690-709. 25. Huang, H.Z., Lu, F.I., Jia, S.J., Meng, S., Cao, Y., Wang, Y.Q., Ma, W.P., Yin, K., Wen, Z.L., Peng, J.R., Rao, Z.H., Thisse, C., Thisse, B., Meng, A.M. (2007) Amotl2 is essential for cell movements in zebrafish embryo by regulating c-Src translocation. Development 134:979-988. 24. Meng, C.Y., Chen, J., Peng, J.R., and Wong S.M. (2006) Host-induced avirulance of Hibiscus chlorotic ringspot vitus mutants correlates with reduced silencing suppression activity. J. Gen. Virol. 87: 451-459. 23. Jin, H., Xu, J., Qian, F., Du, L., Tan, C.Y, Lin, Z.X., Peng, J.R., and Wen, Z.L. (2006) The 5’zebrafish scl promoter targets transcription to the brain, spinal cord, and hematopoietic and endothelial progenitors. Developmental Dynamics 235:60-67. 22. Ren, C.M., Pan, J.W., Peng, W., Genschik, P., Hobbie, L., Hellmann, H., Estelle, M., Gao, B.D., Peng, J.R., Sun, C.Q., and Xie, D.X. (2005) Point mutations in Arabidopsis Cullin1 reveal its essential role in jasmonate response. Plant Journal 42:514-524. 21. Wu, W., Liu, X., Xu, M., Peng, J.R., and Setiono, R. (2005) A hybrid SOM-SVM approach for the zebrafish gene expression analysis. Genomics Proteomics Bioinformatics 3:84-93. 20. Yu, H., Ito, T., Zhao, YX., Peng J.R., Kumar, P., and Meyerowitz, E. (2004) Floral homeotic genes are targets of gibberellin signaling in flower development. Proc. Natl. Acad. Sci. USA. 101:7827-7832. 19. Hynes, L.W., Richards, D.E., Peng J.R., and Harberd, N.P. (2003) Transgenic expression of the Arabidopsis DELLA proteins GAI and gai confers altered gibberellin response in tobacco. Transgenic Research 12:707-714. 18. Fu, X.D., Richards, D.E., Ait-ali T., Hynes, L.W., Ougham H., Peng, J.R., and Harberd, N.P. (2002) Gibberellin-mediated proteasome-dependent degradation of the barley DELLA-protein SLN1 repressor. Plant Cell 14:3191-3200. 3 17. Peng, J.R., Richards, D.E., Moritz, T., Ezura, H., Carol, P., and Harberd, N.P. (2002) Molecular and physiological characterization of Arabidopsis GAI alleles obtained in tageted Ds-tagging experiments. Planta 214:591-596. 16. Fu, X.D., Sudhakar, D., Peng, J.R., Richards, D.E., Christou, P., and Harberd, N.P. (2001) Expression of Arabidopsis GAI in transgenic rice represses multiple gibberellin responses. Plant Cell 13:1792-1802. 15. King, K.E, Carol P, Cowling R.J, Peng J.R., Richards D.E, et al. (2000) Genetic approaches to the understanding of gibberellin-media-ted plant growth regulation. In Molecular Approaches to the Understanding of Plant Hormones, ed. Palme, Schell. New York: Springer-Verlag. 14. Richards, D.E., Peng, J.R., and Harberd, N.P. (2000) Plant GRAS and metazoan STATs: one family? BioEssays 22:573-577. 13. Peng, J.R., Richards, D.E., Hartley, N.M., Murphy, G.P., Devos, K.M., Flintham, J.E., Beales, J., Fish, L.J., Worland, A.J., Pelica, F., Sudhakar, D., Christou, P., Snape, J.W., Gale, M.D., and Harberd, N.P. (1999) ‘Green revolution’ genes encode mutant gibberellin response modulators. Nature 400:256-261. 12. Peng, J.R., Richards, D.E., Moritz, T., Cano, A., and Harberd, N.P. (1999) Extragenic suppressors of the Arabidopsis gai mutation alter the dose-response relationship of diverse gibberellin responses. Plant Physiology 119:1199-1208. 11. Harberd, N.P., King, K.E., Carol, P., Cowling R.J., Peng, J.R., and Richards, D.E (1998) Gibberellin: inhibitor of an inhibitor of ---? BioEssays 20:1001-1008. 10. Peng, J.R., Carol, P., Richards, D.E., King, K.E., Cowling, R., Murphy, G.P., and Harberd, N.P. (1997) The Arabidopsis GAI gene defines a signalling pathway that negatively regulates gibberellin responses. Genes & Development 11:3194-3205. 9. Peng, J.R. and Harberd, N.P. (1997) Gibberellin deficiency and response mutations suppress the stem elongation phenotype of phytochrome-deficient mutants of Arabidopsis. Plant Physiology 113:1051-1058. 8. Peng, J.R., and Harberd, N.P. (1997) Transposon-associated somatic gai-loss sectors in Arabidopsis. Plant Science 130:181-188. 7. Carol, P., Peng, J.R., and Harberd, N.P. (1995) Isolation and preliminary characterization of gas1-1, a mutation causing partial suppression of the phenotype conferred by the gibberellin-insensitive (gai) mutation in Arabidopsis thaliana (L) Heyhn. Planta 197:414-417. 6. Peng, J.R, and Harberd, N.P. (1993) Derivative alleles of the Arabidopsis gibberellin-insensitive (gai) mutation confer a wild-type phenotype. Plant Cell 5:351-360. 5. Whitelam, G.C., Jonson, E., Peng, J.R., Carol, P., Anderson, M., Cowl, J., and Harberd, N.P. (1993) Phytochrome A null mutants of Arabidopsis display a wild-type phenotype in white-light. Plant Cell 5:757-768. 4. Peng, J.R., and Sun, C. (1991) Purification and certain characteristics of a Rhamnose specific lectin in the haemolymph of Philosamia cynthia ricini. Chinese Journal of Biochemistry and Biophysics 4 (in English) 24:279-285. 3. Peng, J.R., and Sun C. (1991) The dynamic changes of two lectins' activities in various tissues during different development stages of Philosamia cynthia ricini. Chinese Journal of Entomology (in Chinese) 34:135-140. 2. Peng, J.R., and Xu, T.S. (1990) 5-L-Oxoprolinase in Bombyx mori and the effects of juvenile hormone analogs ZR512. Chinese Journal of Entomology (in Chinese) 33:143-147 1. Zhao, Z.A., Li, W.S., Peng, J.R., and Gu, Q.M. (1990) Partial purification and characterization of wheat bran polyphenoloxidase. Journal of Fudan University (in Chinese) 29:318-326. Book Chapters: 1. Peng, JR. (1995). Gibberellin and plant development. In The Molecular Basis of Plant Development, Xu, Z.H., & Liu, C.M. eds (Chinese Academy of Science press), pp162-169. 2. Peng, JR. (1995). Plant "fly": Arabidopsis thaliana. In The Molecular Basis of Plant Development, Xu, Z.H., & Liu, C.M. eds (Chinese Academy of Science press), pp225-237. 3. Luo, D., and Peng, JR. (1994). Methods in plant molecular genetics. In Genetic Engineering in Plant, Tian B. ed (Chinese Academy of Science press), pp . 4. Harberd, N., Peng, JR., and Carol P. (1994). Genetic and molecular analysis of plant shape and form using Arabidopsis thaliana as a model system. In Shape and Form in Plants and Fungi, Ingram, D.S., & Hudson, A. eds (for Linnean Society of London by Academic Press), pp241-248. 5. Harberd, NP., and Peng, JR (1991). The Arabidopsis genome and the study of plant morphogenesis. In Plant Sciences Today, Ed. Inra, (Les Colloques no59, Paris), pp13-15. 6. Peng, JR., and Sun, C. (1988). Insect Lectin. Chemistry of Life Sciences (in Chinese) 8:3-4 176 pp. 5 RESEARCH PROJECTS 1. Genetic and genomic approaches to study liver initiation and development in Zebrafish The liver is one of the largest internal organs in the body and is well-known as the main organ for maintaining homeostasis by forming bile, cholesterol, heparin and plasma proteins, regulating blood sugar, lipids and amino acids, as well as storing blood and vitamins. In addition, liver is also the main organ for detoxification. Although its role in maintaining homeostasis is well studied, liver initiation and development are poorly studied through genetic approach and only handful information has been obtained from in vitro tissue culture and tissue explantation experiments. Due to some of its unique advantages for genetic studies: external development and optical clarity during embryogenesis allowing for visual analysis of early developmental processes, and high fecundity and short generation time facilitating genetic analyses, zebrafish (Danio rerio) has been chosen as a model system for the study of vertebrate development. Our goal is to identify genes involved in liver initiation and development in zebrafish. We have obtained and preliminarily characterized 19 independent liver defect mutant lines through screening progenies of ~650 mutagenized families. Our final goal is to clone these mutant genes via positional cloning method in hope to reveal how these genes are involved in controlling liver development. A panel of genetic markers has been established for genetic mapping. Three mutant genes have been cloned via mapbased cloning method. We are currently focusing on identifying the molecular mechanism behind the mutant phenotype observed. In addition, a liver defect mutant caused by the viral vector insertion was obtained from Nancy Hopkins’ lab. Further characterization showed that the viral vector is inserted in a novel gene named as def (digestive-organ-expansion-factor). Loss-of-function of def selectively upregulates the expression of a newly identified p53 isoform 113p53 (human counterpart 133p53) that leads to up-regulation of cell-cycle-related genes but not apopototic-related genes to arrest the expansion growth of the major digestive organs, including liver. In addition, our lab has obtained ~15,000 unique cDNA clusters via our EST sequencing project. At the same time, we have setup microarray facility with optimized methods and conditions. Two batches of zebrafish cDNA microarrays have generated using these unique EST clusters. Combining the use of Affymetrix zebrafish genechip and in-house generated zebrafish cDNA microarrays, we have obtained 129 genes that are genuinely enriched in the adult liver. 69 of these liver-enriched genes are also found to be enriched in the embryonic liver via whole-mount in situ hybridization. These 69 genes will be subjected for the functional studies via morpholino-mediated gene knock-down method to understand if and how they are involved in the liver development. Eventually, target-selected mutagenesis (TILLING method) will be carried out to identify mutants corresponding to interesting genes selected from morpholino studies. The combination of forward genetics and reverse genetics studies will no doubt strengthen our understanding of the molecular mechanism of the liver development. 2. Towards Dissecting GA signalling in Arabidopsis Gibberellins (GA) are one class of phytohormones that has profound and diverse effects on plant growth and development. These effects include the induction of seed germination, the promotion of hypocotyl and stem elongation, the regulation of pollen development and flower initiation etc. However, the molecular mechanisms of GA actions are basically unknown. To understand GA action, factors involved in their signal perception and transduction must be isolated and characterized. The Arabidopsis gai (for gibberellic acid insensitive) is a semi-dominant mutation, which confers a dark-green, dwarf phenotype with elevated endogenous GA levels. Dominant mutations conferring similar phenotypes are known in other plants as well, including maize (D8 mutations) and wheat (Rht mutations). The wheat Rht mutations are especially important because they are the genetic basis of the high-yielding, semi-dwarf wheat varieties of the “green revolution”. Recently, we have cloned GAI/RGA/d8/Rht genes from Arabidopsis, maize and wheat, respectively, and found that these genes are orthologues. These genes encode proteins that resemble nuclear transcription factors and contain an SH2-like domain. We have proposed that these proteins are plant equivalents of the 6 metazoan STATs and that a conserved phosphotyroine may participate in GA signalling. One of the main aims of this group is to identify more genes that are involved in GA signalling and to gain an understanding of the biochemical functions of their encoded products. 7