Research

Joseph R. Ecker, a professor in the Plant Biology Laboratory, is one of the nation's leading authorities on the molecular biology and genetics of plants. Ecker was a principal investigator in the multinational project that sequenced the genome of Arabidopsis thaliana,  a modest weed that has become a model organism for the study of plant genetics. This wild mustard variety is the first plant to have its genome sequenced, an achievement expected to have widespread implications for agriculture and perhaps human medicine as well.

Ecker is also widely regarded as one of the foremost experts on how the gaseous hormone ethylene regulates a variety of basic plant processes. For agriculture, ethylene gas is a vital chemical messenger important for such processes as fruit ripening and how plants respond to pathogenic organisms.

"Nature vs. nurture, genes vs. environment—what is more important? My group is interested in understanding the roles of genetic and 'epigenetic' processes in cell growth and development. By understanding how the genome and epigenome talk to one another, we hope to be able to untangle the complexity of gene regulatory processes that underlie development and disease in plants and humans."

Although the human genome sequence lists almost every single DNA base of the roughly 3 billion bases that make up a human genome, it doesn't tell biologists much about how its function is regulated. That job belongs to the epigenome, the layer of genetic control beyond the regulation inherent in the sequence of the genes themselves. Being able to study the epigenome in its entirety promises a better understanding of how genome function is regulated in health and disease, as well as how gene expression is influenced by diet and the environment.

One of the ways epigenetic signals can tinker with genetic information is through DNA methylation, a chemical modification of one letter, C (cytosine), of the four letters (A, G, C, and T) that comprise our DNA. In the last couple of years, Ecker's laboratory started to zero in on genomic methylation patterns, which are essential for normal development and associated with a number of key cellular processes, including carcinogenesis.

To ascertain how the epigenome of a differentiated cell differs from the epigenome of a pluripotent stem cell, his team used an ultra-high-throughput methodology to determine precisely whether or not each C in the genome is methylated and to layer the resulting epigenomic map upon the exact genome it regulates. The study revealed a highly dynamic, yet tightly controlled, landscape of chemical signposts known as methyl groups and resulted in the first detailed map of the human epigenome, comparing the epigenomes of human embryonic stem cells and differentiated connective cells from the lung called fibroblasts. The head-to-head comparison brought to light a novel DNA methylation pattern unique to stem cells, which may explain how stem cells establish and maintain their pluripotent state.

Now that they are able to create highresolution maps of the human epigenome, Ecker's group will begin to examine how it changes during normal development as well as in a variety of disease states.

Standing, left to right: Shelly Wanamaker, Michael Ho, Junshi Yazaki, Huaming Chen, Liang Song, Shao-shan Carol Huang, Hong Qiao, Mingtang Xie, Anna Bartlett, Mark Urich, Rosa Castanon, Raul Carlos Serrano, Bennett Ouchi, Alanna Gordon, Cesar Barragan, Lantian Gai

Sitting, left to right: Nancy Benson, Alice Kim, Rick McCosh, Mark Zander, Bob Schmitz, Matt Schultz, Ronan O'Malley, Joe Ecker, Joe Nery, Adeline Goubil, Mat Lewsey, Bruce Jow, Thomas Ng, Justin Sandoval, Sage Davis

Selected Publications

Alonso, J.M., Stepanova, A.N., Leisse, T.J., Kim, C.J., Chen, H., Shinn, P., Stevenson, D.K., Zimmerman, J., Barajas, P., Cheuk, R., Gadrinab, C., Heller, C., Jeske, A., Koesema, E., Meyers, C.C., Parker, H., Prednis, L., Ansari, Y., Choy, N., Deen, H., Geralt, M., Hazari, N., Hom, E., Karnes, M., Mulholland, C., Ndubaku, R., Schmidt, I., Guzman, P., Aguilar-Henonin, L., Schmid, M., Weigel, D., Carter, D.E., Marchand, T., Risseeuw, E., Brogden, D., Zeko, A., Crosby, W.L., Berry, C.C. and Ecker. J.R., (2003) Genome-wide Insertional mutagenesis of Arabidopsis thaliana. Science. 301:653-657.

Yamada K, Lim J, Dale JM, Chen H, Shinn P, Palm CJ, Southwick AM, Wu HC, Kim C, Nguyen M, Pham P, Cheuk R, Karlin-Newmann G, Liu SX, Lam B, Sakano H, Wu T, Yu G, Miranda M, Quach HL, Tripp M, Chang CH, Lee JM, Toriumi M, Chan MM, Tang CC, Onodera CS, Deng JM, Akiyama K, Ansari Y, Arakawa T, Banh J, Banno F, Bowser L, Brooks S, Carninci P, Chao Q, Choy N, Enju A, Goldsmith AD, Gurjal M, Hansen NF, Hayashizaki Y, Johnson-Hopson C, Hsuan VW, Iida K, Karnes M, Khan S, Koesema E, Ishida J, Jiang PX, Jones T, Kawai J, Kamiya A, Meyers C, Nakajima M, Narusaka M, Seki M, Sakurai T, Satou M, Tamse R, Vaysberg M, Wallender EK, Wong C, Yamamura Y, Yuan S, Shinozaki K, Davis RW, Theologis A, and Ecker JR. (2003) Empirical analysis of transcriptional activity in the Arabidopsis genome. Science. 302:842-846.

Guo, H., and Ecker J.R. (2003) Plant Responses to Ethylene Gas Are Mediated by SCFEBF1/EBF2-dependent Proteolysis of EIN3 transcription factor. Cell. 115: 667-677.

Wang, K. L., Yoshida, H., Lurin, C., and Ecker, J. R. (2004). Regulation of ethylene gas biosynthesis by the Arabidopsis ETO1 protein. Nature. 428, 945-950.

Li, H., Johnson, P., Stepanova, A., Alonso, J. M., and Ecker, J. R. (2004). Convergence of signaling pathways in the control of differential cell growth in Arabidopsis. Dev Cell. 7, 193-204.

Mockler TC, Chan S, Sundaresan A, Chen H, Jacobsen SE, Ecker JR. (2005) Applications of DNA tiling arrays for whole-genome analysis. Genomics. 85(1):1-15.

Alonso, J.M. and J.R. Ecker (2006) Moving forward in reverse: genetic technologies to enable genome-wide phenomic screens in Arabidopsis. Nat. Rev. Genet. 7:524-

Olmedo, G., G. Guo, B.D. Gregory, S.D. Nourizadeh, L. Aguilar-Henonin, H. Li, H. An, P. Guzman, and J.R. Ecker (2006) ETHYLENE-INSENSITIVE5 encodes a 5'→3' exoribonuclease required for regulation of the EIN3-targeting F-box proteins EBF1/2. Proc Natl Acad Sci U S A, |. 103: 13286-13293

Zhang, X., Yazaki, J., Sundaresan, A. Cokus,S., Chan, S.W.-L., Chen, H., Henderson, I.R., Shinn, P., Pellegrini, M., Jacobsen, S.E., and Ecker, J.R. (2006) Genome-wide high-resolution mapping and functional analysis of DNA methylation in Arabidopsis. Cell. 126, 1189-1201

Clark, RM, Schweikert, G., Toomajian, C., Ossowski, S., Zeller, G., Shinn, P., Warthmann, N., Hu, T.T., Fu, G., Hinds. D.A. , Chen, H., Frazer, K.A., Huson, D.H., Schölkopf, B., Nordborg, M., Rätsch, G., Ecker. J. R., and Weigel, D. (2007) Common sequence polymorphisms shaping genetic diversity in Arabidopsis thaliana. Science. 317(5836):338-42

Lister, R., O'Malley, R.C., Tonti-Filippini, J., Gregory, B.D., Berry, C.C., Millar, A.H. and Ecker, J.R. (2008) Highly integrated single-base resolution maps of the epigenome in Arabidopsis. Cell. 133:1-14 | Download the article

Lister, R., Pelizzola, M., Dowen, R.H, Hawkins, R.D., Hon, G., Tonti-Filippini, J., Nery, J.R., Lee, L., Ye, Z., Ngo, Q-M., Edsall, L., Antosiewicz-Bourget, J., Stewart, R., Ruotti, V., Millar, A.H., Thomson, J.A., Ren, B. and Ecker, J.R. (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 462:315-322

Lister R., Pelizzola M., Kida Y.S., Hawkins R.D., Nery J.R., Hon G., Antosiewicz-Bourget J., O'Malley R., Castanon R., Klugman S., Downes M., Yu R., Stewart R., Ren B., Thomson J.A., Evans R.M. and Ecker J.R. (2011) Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature Mar 3;471(7336):68-73. Epub 2011 Feb 2.

Evidence for network evolution in an Arabidopsis interactome map. Arabidopsis Interactome Mapping Consortium. Science. 2011 333(6042):601-7.

Mukhtar, M.S., Carvunis, A.R., Dreze, M., Epple, P., Steinbrenner, J., Moore, J., Tasa,n M., Galli, M., Hao, T., Nishimura, M.T., Pevzner, S.J., Donovan, S.E., Ghamsari, .L, Santhanam, B., Romero, V., Poulin, M.M., Gebreab, F., Gutierrez, B.J., Tam, S., Monachello, D., Boxem, M., Harbort, C.J., McDonald, N., Gai, L., Chen. H., He, Y., European Union Effectoromics Consortium, Vandenhaute, J., Roth, F.P., Hill, D.E., Ecker, J.R., Vidal, M., Beynon, J., Braun, P., Dangl, J.L. (2011) Independently evolved virulence effectors converge onto hubs in a plant immune system network. Science. 333(6042):596-601.

Schmitz, R.J., Schultz, M.D., Lewsey, M.G., O'Malley, R.C., Urich, M.A., Libiger, O., Schork, N.J., Ecker, J.R. (2011) Transgenerational Epigenetic Instability Is a Source of Novel Methylation Variants. Science. 334(6054):369-73. Abstract | Download the article

Qiao, H., Shen, Z., Huang, S.S., Schmitz, RJ., Urich, M.A., Briggs, S.P. and Ecker, J.R. (2012) Processing and Subcellular Trafficking of ER-Tethered EIN2 Control Response to Ethylene Gas. Science 338(6105):390-393. Abstract

Schmitz, R.J., Schultz, M.D., Urich, M.A., Nery, J.R., Pelizzola, M., Libiger, O., Alix, A., McCosh, R.B., Chen, H., Schork, N.J. and Ecker, J.R. (2013) Patterns of population epigenomic diversity. Nature. Mar 14;495(7440):193-8. doi: 10.1038/nature11968. Epub 2013 Mar 6. Link

Salk News Releases

• Hidden layer of genome unveils how plants may adapt to environments throughout the world
  March 6, 2013
• More than 3,000 epigenetic switches control daily liver cycles
  December 10, 2012
• Two more Salk scientists elected as AAAS Fellows
  November 29, 2012
• Discovery may help protect crops from stressors
  August 30, 2012
• Planting the seeds of defense
  August 7, 2012
• Are genes our destiny?
  September 15, 2011
• Scientists take a giant step for people - with plants!
  July 28, 2011
• Salk scientist Joseph Ecker, appointed as Howard Hughes Medical Institute and Gordon and Betty Moore Foundation Investigator
  June 16, 2011
• Cell reprogramming leaves a "footprint" behind
  February 2, 2011
• What drives our genes? Salk researchers map the first complete human epigenome
  October 14, 2009
• Why fruits ripen and flowers die:
  Salk scientists discover how key plant hormone is triggered
  February 10, 2009
• Not your grandfather's transcriptome-plant biologists discover unexpected proteins affecting small RNAs
  May 15, 2008
• Charting the Epigenome
  April 17, 2008
• New plant study reveals a "deeply hidden" layer of the transcriptome
  December 27, 2007
• Charting ever-changing genomes
  July 19, 2007
• National Academy of Sciences honors Joe Ecker with Carty Award
  January 25, 2007
• In a technical tour de force, Salk scientists take a global view of the epigenome
  August 31, 2006
• Salk scientist Joe Ecker elected to National Academy of Sciences
  April 25, 2006
• Gene Chip Study Could Lead to New Hybrid Plants
  October 31, 2003
• Salk Study Advances Understanding of Plant Genes and Their Function
  July 31, 2003
• First Plant Genome Sequenced: Salk Scientists Part Of International Effort
  December 13, 2000

Awards and Honors

• 2011 Investigator, Howard Hughes Medical Institute and the Gordon and Betty Moore Foundation
• 2011 George W. Beadle Award, Genetics Society of America
• 2009 #2 Scientific Discovery of the Year 2009-TIME Magazine
• 2007 National Academy of Sciences, John J. Carty Award for the Advancement of Science
• 2006 Elected, National Academy of Sciences
• 2005 American Society for Plant Biology, Martin Gibbs Medal
• 2004 Scientific American 50 Research Leader of the Year
• 2004 International Plant Growth Substances Association Distinguished Research Award
• 2001 Kumho Science International Award in Plant Molecular Biology
• President International Society for Plant Molecular Biology

Links

Ecker lab

San Diego Center for Molecular Agriculture - for information on genetically modified crops

Ecker technologies available for licensing

TIME Ranks Epigenome Study No. 2 Scientific Discovery of 2009

See TIME magazine story>>

See NBC coverage of the Epigenome Study>>

Read the press release of the Epigenome Study>>

Cell reprogramming leaves a "footprint" behind

February 02, 2011

Reprogramming adult cells to recapture their youthful "can-do-it-all" attitude appears to leave an indelible mark, found researchers at the Salk Institute for Biological Studies. When the team, led by Joseph Ecker, PhD., a professor in the Genomic Analysis Laboratory, scoured the epigenomes of so-called induced pluripotent stem cells base by base, they found a consistent pattern of reprogramming errors. Read more>>

What drives our genes? Salk researchers map the first complete human epigenome

September 9, 2010

Although the human genome sequence faithfully lists (almost) every single DNA base of the roughly 3 billion bases that make up a human genome, it doesn't tell biologists much about how its function is regulated. Now, researchers at the Salk Institute provide the first detailed map of the human epigenome, the layer of genetic control beyond the regulation inherent in the sequence of the genes themselves. Read more>>