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July 2011


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NIEHS at Society for In Vitro Biology meeting

By Eddy Ball
July 2011

Pierre Bushel, Ph.D. and Leping Li, Ph.D.

Symposium conveners Bushel, smiling in background left, and Li, foreground, listened to and sometimes laughed along with presenters. Not shown are fellow conveners Lia Campbell, Ph.D., director of research at Cell and Tissue Systems, Inc., and Prakash Lakshmanan, Ph.D., lead for the molecular breeding program at the David North Plant Research Centre. (Photo courtesy of Steve McCaw)

Mei Guo, Ph.D.

Guo showed photos illustrating the dramatic variation in size among vegetable strains. Her group manipulates candidate genes with the goal of increasing crop output. (Photo courtesy of Steve McCaw)

Sailu Yellaboina, Ph.D.

Yellaboina was making his final presentation as an NIEHS postdoc. In mid June, he left for a post at the C.R. Rao Advanced Institute of Mathematics, Statistics, and Computer Sciences in his native India. (Photo courtesy of Steve McCaw)

NIEHS scientists contributed their bioinformatics expertise to a weeklong meeting of the Society for In Vitro Biology(http://www.sivb.org/index.html) Exit NIEHS annual meeting June 4-8 in Raleigh. They joined hundreds of plant and animal biologists from the government, academia, nonprofit, and private sectors for a discussion of topics ranging from proof-of-principle research to product development.

NIEHS Biostatistics Branch Principal Investigator Leping Li, Ph.D.,(http://www.niehs.nih.gov/research/atniehs/labs/bb/staff/li/index.cfm) and Staff Scientist Pierre Bushel, Ph.D.,(http://www.niehs.nih.gov/research/atniehs/labs/bb/staff/bushel/index.cfm) served as conveners of the plenary symposium "Bioinformatics/Statistics in Research and Product Improvement" featuring presentations on the power of bioinformatics discovery in agronomy, embryonic stem cell biology, and cancer. Former NIEHS Biostatistics Branch Visiting Fellow Sailu Yellaboina, Ph.D., (see story(http://www.niehs.nih.gov/news/newsletter/2011/june/spotlight-postdoc/index.cfm)) gave one of the three presentations at the symposium.

As the symposium organizers maintain, data from microarrays, next generation sequencing, and single nucleotide polymorphism analysis continue to proliferate, leading to "the need to integrate these data sets and analysis results for a more informed interpretation of biological consequences and phenotypic events."

Looking at the end result

The opening talk of the session was presented by research agronomist Mei Guo, Ph.D., of DuPont's Pioneer Hi-Bred International(http://www.pioneer.com/home/site/us) Exit NIEHS, a producer of genetically engineered crops to improve yield and hardiness, as well as provide greater insect and disease resistance. While she focused more on genetic engineering than on the bioinformatics of candidate gene discovery, the dramatic results of her research underscored the important role of bioinformatics in helping select candidate genes.

Guo's team manipulated expression of two cell number regulator (CNR) genes in corn, downregulating ZmCNR01 and overexpressing ZmCNR02, to increase the stalk height, overall biomass, and number of kernels on each ear by as much as 20 percent. Guo noted that each addition kernel ring on an ear of corn increases per acre yield by at least five percent.

Investigating genes involved in embryonic stem cell maintenance

As Yellaboina explained when he began his talk, "ES (embryonic stem) cell therapies have been proposed for regenerative medicine and tissue replacement after injury or disease," because these cells maintain an epigenetic state that enables both self-renewal and differentiation into any of the cellular systems of the adult body. However, he pointed out, in order to utilize their remarkable properties, scientists need to better understand the genes essential for the self-renewal and pluripotency and how to manipulate them to influence the timing and direction of ES cell differentiation.

According to Yellaboina, some 400 genes have been identified in previous genome-wide screenings as playing a role in maintenance of ES cell identify. "We undertook a massive effort to integrate approximately 30 previously published gene expression microarray datasets in mouse ES cells and differentiated cells across various developmental stages," he explained. The researchers used a meta-analysis approach to rank all the genes in order of their likelihood to be required for ES cell maintenance and performed RNA interference screens to examine 25 previously unscreened genes ranked in the top 500.

Although he conceded, "the picture of self-renewal still remains largely incomplete," the group has developed a systematic approach to gain systems-level understanding of ES cell maintenance.

An integrated approach to studying epigenetics

The final speaker at the symposium was computational biologist Guo-Cheng Yuan, Ph.D.(http://www.hsph.harvard.edu/faculty/guocheng-yuan/) Exit NIEHS, an assistant professor at the Harvard School of Public Health and Dana-Farber Cancer Institute.

As Yuan said at the beginning of his talk, epigenetic alterations are the result of several discrete factors working in concert. Insights into Polycomb group (PcG) genes targeting mechanisms that promote histone trimethylation in mammals may help scientists better understand how stem cell identity is maintained.

Yuan reported on the analysis of genome-wide ChIP-chip data on several PcGs related to epigenetic modification, explaining that changes in PcG targeting patterns are well coordinated with alterations in gene expression. Yuan also said that his model performs well and over 90 percent of the top 400 predicted genes were correct targets and that the genes that have high prediction scores tend to be associated with H3K27me3 in multiple cell lines.

Statue of Sir Walter Raleigh dressed to support the Susan G. Komen Race for the Cure

As scientists discussed their research inside, a statue of Sir Walter Raleigh in front of the Raleigh Convention Center showed the city's support for the Susan G. Komen Race for the Cure taking place the following weekend. (Photo courtesy of Steve McCaw)

Guo-Cheng Yuan, Ph.D.

Yuan's group develops statistical and computational methodologies for genomic data analysis and integration, with the aim of characterizing systems-level gene regulatory mechanisms. (Photo courtesy of Steve McCaw)

The presenters and their collaborators

Abstracts for the talks in the bioinformatics plenary symposium have been posted online (http://www.sivb.org/2011MeetingPDFs/PlenarySymposia.pdf)  Download Adobe ReaderExit NIEHS (88 KB) by the Society for In Vitro Biology.

  • PS-7 Utilizing Bioinformatics in Identification and Functional Analysis of Cell Number Regulator Genes in Diverse Plant Species for Crop Improvement of Maize - A Whole Different Animal. Mei Guo, Mary A. Rupe, Jo Ann Dieter, Jijun Zou, Daniel Spielbauer, Keith E. Duncan, Richard J. Howard, Zhenglin Hou, and Carl R. Simmons. Pioneer Hi-Bred, A DuPont Business, Johnston, Iowa, and DuPont Crop Genetics Research, Wilmington, Del. Email: mei.guo@pioneer.com
  • PS-8 Integrating Genomic Datasets to Understand the Mechanisms of Embryonic Stem Cell Maintenance. Sailu Yellaboina, Xiaofeng Zheng, Dmitri Zaykin, Guang Hu, and Raja Jothi. Biostatistics Branch and Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, N.C. 27709. Email: yellaboinas@mail.nih.gov
  • PS-9 Query of Polycomb Targeting Mechanism in Mammals by Integration of Experimental and Computational Methods. Guo-Cheng Yuan. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Department of Biostatistics, Harvard School of Public Health. Email: gcyuan@jimmy.harvard.edu


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