facilitieshcs

High-Content Screening Shared Research Facility

location:

Annenberg Building

1468 Madison Avenue

18th Floor, Room 21

New York, NY 10029

tel: 212-241-6866

fax: 212-860-9279

contacts:

Dan Felsenfeld, PhD, Director
dan.felsenfeld@mssm.edu

tel: 212-241-4296

Marek Mlodzik, PhD, Director
marek.mlodzik@mssm.edu

tel: 212-241-6516

Overview

This newly established SRF, now in its initial phase of organization, provides high-content and high-throughput screening techniques based on fluorescent microscopy and spectroscopy to the Mount Sinai community. Imaging-based assays, once restricted to cell and developmental biology, have become a critical component in a broad spectrum of basic and clinical research. The development of novel fluorescent probes combined with improvements in robotics and computer-assisted feature recognition, has facilitated the development of commercial microscopes capable of high-throughput evaluation of image-based assays.

Microscopy-based assays permit the detection of molecular events in the context of their cellular environment and complement other high-throughput genomic and proteomic techniques that examine primarily changes that occur en mass. Those technologies can’t detect local changes in cell physiology that are obscured when cell homogenates are used as a starting point for assays. Microscopy directly measures physiological events reflected through changes in protein distribution or cell morphology. For instance, using fluorophore-conjugated reporters that alter their subcellular distribution in response to physiological signals, it is possible to quantify changes in cell physiology on a single-cell basis. Similarly, fluorescent reporters that alter their spectra based on the concentration of a signaling molecule or activity of a specific kinase permit the detection of a wide variety of signaling pathways in their cellular context. In combination with new automated microwell-based microscopes, these reporters permit the evaluation of libraries of compounds or siRNA reagents on a high-throughput basis using changes in cell-structure as the primary method of evaluation.

This SRF therefore complements existing high throughput methods at Mount Sinai. Staff will assist end users in assay design, equipment automation, programming and automated feature recognition. We estimate that we will be able to evaluate a library of 14,000-20,000 siRNA (small interfering RNA) pools or small compounds over the course of 3-5 days. siRNA libraries are directed primarily at identifying the critical components of pathways under consideration (drug targets). Compound libraries will be screened to identify drug candidates that modulate those targets.

This new facility is expected to be fully functional in the third quarter of 2008.

... in progress

hardware:

... in progress

software:

... in progress