DAVID H. SHERMAN, PH.D.
DIRECTOR, CENTER FOR CHEMICAL GENOMICS
MARTHA J. LARSEN, M.S.
DIRECTOR, HTS, SIRNA, HCS LABORATORY
CENTER FOR CHEMICAL GENOMICS
THE UNIVERSITY OF MICHIGAN, LIFE SCIENCES INSTITUTE
210 WASHTENAW AVENUE
ANN ARBOR, MICHIGAN 48109-2216
734-615-9537; FAX 734-763-6492
DATE
Dear name,
We are delighted to assist you in your grant type application entitled enter proposal name. This proposal
involves description. [If appropriate: This work is based upon your details on previous targets/screens that
were conducted in the Center for Chemical Genomics (CCG) in the University of Michigan’s Life Sciences
Institute.]
The HTS director and her research staff have extensive experience with assay development and screening
technology. For example, we perform over 20 screens per year director to add details. In total, we have
performed 80+ screens for UM faculty, external academic groups and both large and small pharmaceutical
companies. The results of 35+ CCG projects have been published and 40+ CCG pilot screens have received
subsequent grant support. Specific to your proposal, director fills in details here. With your experience in
please fill in details, this project should be successful in please fill in details here.
Another purpose of this letter is to outline the capabilities of the CCG, which includes modern screening
instrumentation, chemical libraries, RNAi collections and high content analysis. Of particular note is our
180,000+ chemical library, which includes ~ 30,000 natural product extracts, ~100,000 diverse compounds
and a number of focused libraries. The HTS Core staff work hand-in-hand with your laboratory members to
develop, miniaturize and implement the assay. In addition, CCG staff and faculty advisors are committed to
working closely with you after the HTS campaign; we will assist in data interpretation and in designing
appropriate follow-up analyses to separate false positives from informative hits. Finally, we can help you in
the design of appropriate structure-activity studies that will advance your initial “hits” to more potent and
selective chemical tools. Often, this process will also involve the Hans G. Vahlteich Medicinal Chemistry
Core, which is staffed by experienced, industry-trained medicinal chemists. Finally, the CCG enters all
results into a custom database, M-screen, which is an effective tool for storing, retrieving and archiving
screening data. MScreen also allows comparative meta-analysis of multiple screening targets, which helps
separate off-target effects from hits of interest. Through MScreen, you can also upload results to public
databases, such as PubChem. We greatly look forward to working with you on your project.
Sincerely,
David H. Sherman
Hans W. Vahlteich Professor of Medicinal Chemistry
Professor of Chemistry
Professor of Microbiology & Immunology
Director, CCG
Martha J. Larsen
Assistant Research Scientist
Director, HTS, siRNA, HCS Laboratory
CCG Resources
Chemical and RNAi Libraries
150,000+
diverse small molecule compounds
2,446
FDA-approved drugs and known bioactives
1200+
focused libraries (autophagy, kinases, epigenetics)
2830
fragment library
30,000+
natural product extracts
20M
in silico library available for searching
siRNA
Dharmacon human and mouse druggable genomes
Liquid Handling Robotics
Mosquito X1 (TTP Labtech), a hit-picking liquid handler with 96- and 384-well plate formats, 251200 nL positive displacement tips for confirmation, serial dilutions and reagent/sample
transfers
Beckman Biomek FX multi/multi- 96-well pipetter head & 384 pipetter head
Beckman Biomek FX - 384-well nanoliter HDR (pin tool)
Sciclone ALH3000 – 384- and 1536-well nanoliter V&P pin tool
Thermo Multidrop and Micromultidrop 96-384 liquid dispensers
Thermo Combi Multidrops liquid dispensers
Thermo Combo nl liquid dispenser for 96, 384 & 1536 plates
Catalyst Express Robotic arm and plate storage
Bio-Tek ELx405 and 406 Plate Washers
CaliperLS Twister II plate hotel
Detection equipment
BMGLabtech PHERAstar high-speed, multifunction plate reader
Detection capabilities including 96-, 384-well: absorbance, fluorescence, fluorescence
polarization, time-resolved fluorescence, time-resolved FRET, and luminescence
Molecular Devices FlexStation3 with 5 assay formats: kinetic, endpoint, spectrum, well-scanning
and Flex mode for bottom read capacity in calcium mobilization and membrane potential assays.
Application technologies in 96-, 384-well: absorbance, fluorescence intensity, fluorescence
polarization, luminescence and time-resolved fluorescence with dual monochromators.
HyperCyt/Accuri-The HyperCyt high throughput liquid handling front-end moves microliter samples
from 384-well plates and rapidly delivers them to the Accuri flow cytometer. Both bead and cell
samples can be used and a 384-well plate can be analyzed in 10 min providing a throughput of
over 2000 compounds per hour.
MDS Analytical Technologies-ImageXpress Micro Cellular Imaging and Analysis System for
automated acquisition and analysis of images for high throughput cell-based screening. Includes
Acuity Xpress Informatics and MDCStore database.
PE EnVision Multimode Plate Reader
Detection for all non-isotopic detection technologies, including fluorescence intensity,
fluorescence polarization, time-resolved fluorescence (TRF), luminescence (enhanced) and
absorbance (monochromator), BRET and AlphaScreen in 96-, 384 and 1536-well formats.
Informatics
Web database using Oracle:
Relational database of compounds, plate inventory, results
Results browsing or searching
Comparison of results among different screens
Structure similarity searches on external library to find compounds for SAR
Links to public databases for chemical and biological profiling
ICM Chemist (Molsoft LLC)
Chemical spreadsheet, Chemical structure clustering, SAR Analysis