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Genomic Tools Summit

Co-located CHI Event:
Genomic Tools & Technologies Summit
June 8-10, 2009
San Francisco, CA

AppliedBiosystems

MitoProd

ThermoScientific

ISCB

Bio-IT World

biophotonics

GEN

Genome Medicine

Nature

SJBC

Science AAAS

The Scientist

RNAi for Functional Screens - Day 1

 

Day 1  |  Day 2Print

 

MONDAY, JUNE 8

7:30 am – 6:00 pm Registration Open


MAIN CONFERENCE

7:30 am Morning Coffee


HARNESSING THE POWER OF GENOME-WIDE SCREENS

8:30 Chairperson’s Remarks

Anthony Orth, Ph.D., Associate Director, Head of Genomics Profiling, Genomics Institute of the Novartis Research Foundation

8:45 Development of a Flexible RNAi Screening Platform for Drug Discovery

Anthony Orth, Ph.D., Associate Director, Head of Genomics Profiling, Genomics Institute of the Novartis Research Foundation

Scanning the genome for druggable targets involved in therapeutically-relevant cellular models has become an increasingly important tool in the pre-clinical drug discovery process.  We have developed an assay system permitting whole genome synthetic siRNA and druggome-scale lentiviral shRNA screening and describe its application, by way of example, to patient-derived glioblastoma.

9:15 Talk Title to Be Announced

Caroline Shamu, Ph.D., Director, ICCB-Longwood Screening Facility,
Harvard Medical School (invited)

9:45 Talk Title to Be Announced

Pedro Aza-Blanc, Ph.D., Director, Functional Genomics Resources,
The Burnham Institute for Medical Research

10:15 Coffee Break

10:45 High-Content Cellular Microarrays for Genome-Wide RNAi Screens

Auguste Genovesio, Ph.D, Principal Investigator and Head of Image Mining Group, Institut Pasteur-Korea

Despite several commercially available platforms for high-content screening, the concrete execution of thousands of visual cell-based experiments has remained highly challenging in terms of both statistical robustness and speed. An efficient computational method for cellular microarrays was developed at Institut Pasteur-Korea for fast, visual genome-wide siRNA screening. This method and some genome-wide analysis results will be presented in this talk.

11:15 Identification of Novel Wnt/β-Catenin Pathway Regulators Using Genome Scale siRNA Screens

William Arthur, Ph.D., Senior Research Biologist, Rosetta Inpharmatics, LLC (A wholly owned subsidiary of Merck & Co., Inc.)

The canonical Wnt/β-Catenin pathway controls several fundamental cellular processes and aberrant regulation of this signaling cascade can result in several disease phenotypes and is a hallmark of colorectal cancer (CRC) and hepatocellular carcinoma (HCC). We have developed a genome scale RNAi screening process that included steps for initial hit identification, mitigation of off-target effects, elimination of cell line-specific effects, and measurement of Wnt/β-Catenin signature regulation. These studies identified 29 previously undescribed regulators of the Wnt/β-Catenin pathway. We further validated a number of these new pathway mediators in vitro for physical association with canonical pathway members and in vivo by use of zebrafish models. Here we highlight AGGF1, which our findings suggest functions in the pathway to recruit or regulate the activity of SWI/SNF in β-Catenin-dependent transcriptional complexes.

11:45 Panel Discussion: Designing and Defining High-Throughput RNAi Screens

12:15 pm Close of Morning of Session

12:30 pm Presentation 1 (Opportunity Available)

1:00 pm Presentation 2 (Opportunity Available) or Lunch on Your Own


EXTENDING THE RANGE OF FUNCTIONAL SCREENS

2:00 Chairperson’s Remarks

2:05 Towards Functional Annotation of the Cancer Genome

Michael A. White, Ph.D., Professor, Cell Biology and Associate Director, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center

2:35 Using HT Applications of RNAi to Drive Drug Discovery and Development

Christophe J. Echeverri, Ph.D., Chief Executive Officer and Chief Scientific Officer, Cenix BioScience GmbH

3:05 Probing the p53 Pathway

Laura Corson, Associate Scientist, Department of Cell Regulation, Genentech Inc.

A multi-parametric, high content siRNA screen of cells +/- p53 yielded insight into genes that impinge on the p53 tumor suppressor pathway. Identification of siRNAs that regulate the strength of the p53 response point to potential tumor supressors, oncogenes, and possible drug targets.

3:35 siRNA Screening: Development of Hit Stratification Strategies  Sponsored by ThermoScientific
Louise C. Baskin, Product Manager, Dharmacon Products, Thermo Fisher Scientific
While synthetic siRNA libraries are powerful tools for functional genomic screens, off-target effects mediated by siRNA seed interactions with the 3’UR of unintended targets can result in false positives. Given this potential, the development of effective hit validation/stratification strategies is imperative. We will present a study that compares two strategies for identification of high confidence hits, including a multiple-reagent approach where two or more individual siRNAs induce the same phenotype and a chemical modification approach where hit confirmation is achieved using pools of siRNAs that contain dual-strand specificity-enhancing modifications.

3:50 Refreshment Break

4:15 High-Throughput RNAi-Based Cellular
Pharmacogenomics Revealed Context of Vulnerabilities of Brostallicin

Holly Yin, Head of Cellular Genomics, Pharmaceutical Genomics Division (PGD), Translational Genomics Research Institute

We applied high-throughput RNAi screen in the attempt to identify molecular determinants of Brostallicin, a minor groove DNA binding agent. From this, we identified two predominant concepts for brostallicin response, DNA repair and histone modification, on which additional studies were focused including confirmation, validation and in vitro drug combinations with Brostallicin. The combined results from this study can inform clinical development and rational drug combination strategies

4:45 To Be Announced

5:15 Welcoming Reception in the Exhibit Hall

6:30 End of Day