CCG Newsletter
News from the CCG:

FEBRUARY 2012
In This Issue
New Staff Member in the CCG
New uHTS Format Instrumentation at CCG
Science Feature
New Staff Member in the CCG
Buchholz headshot
Tonia Buchholz joined the Center for Chemical Genomics (CCG) in November, 2011 as the new Director of Emerging Technologies and External Collaborations. She has specific training and expertise in developing robust assays for drug discovery from her academic and industry experiences (PanVera Corporation, Rigel Pharmaceuticals, Proteolix, Inc., and Enzo Life Sciences). She has designed and optimized biochemical and cell-based assays for internal pharmaceutical research and also for commercial sale for more than 10 years. "Returning to the CCG is a homecoming for me." Tonia performed her doctoral work in Prof. David Sherman's lab and collaborated extensively with Janet Smith and the High Throughput Protein core. "There are many familiar faces around, and the spirit of cooperation and innovation is remarkable."
[Read more].


New uHTS Format Instrumentation at CCG  

By Martha Larsen, HTS Lab Director, CCG

The CCG has expanded its screening capabilities to include 1536-well assay plate formats. High-Throughput Screening (HTS) relies on the ability to assess activity of thousands of compounds in a single biological target in a rapid, reliable, and reproducible format. In this quest, miniaturization of assay plates is one solution to the difficulty of accomplishing the testing of a large collection in minimal time and using expensive reagents. Assays that can be transferred from 96-well to 384-well plates reduce costs by a fourth, shorten plate reader times and reduce reagent needs. The CCG has employed 384-well plates since its inception seven years ago. To date, over 25,000 assay plates have been used to perform screening on over 100 biomedical targets, the vast majority of those were 384-well format. This represents almost 10 million experiments or roughly 7000 per day.  It also represents a tremendous savings to researchers with limited biological supplies or expensive reagents as volumes for 384-well plates are 10-40ul per well instead of the 100ul or more required in 96-well formats. But for some investigators even 10 ul per sample tested is too much when you need to screen over 150,000 wells; that's liters of reagents! Using 1536-well plate format, researchers with ultra HTS (uHTS) amenable assays will be able to complete their screens faster and using less resources. [Read more]

Science Feature - Andrew Fribley, Ph.D., Wayne State University
As a postdoctoral fellow in the laboratory of Randy Kaufman, Howard Hughes Medical Investigator at University of Michigan, Andrew Fribley began investigating the use of high-throughput screening to identify novel small molecules and natural products that could induce the unfolded protein response and selectively kill cancer cells. "I was fortunate to find experienced and helpful collaborators in the Center for Chemical Genomics (CCG). I worked with Dr. Rick Neubig, Co-Director of the CCG and Martha Larsen, HTS Lab Director to develop a robust complementary cell-based screen. After identifying several hits from our primary screen at CCG I was very lucky to enlist the support of medicinal chemists Hollis Showalter and Scott Larsen and computational chemist Paul Kirchhoff who had recently come to the University of Michigan from Pfizer. Together this invaluable team of CCG and MedChem experts worked together to identify, triage and analog a panel of hit compounds which ultimately resulted in two separate R03 grants through the NIH roadmap initiative for high- throughput screening as well as a K 99/R00 pathway to independence award from NIDCR. Working very closely with David Sherman's lab group we have screened more than 5,000 natural products extracts and identified several therapeutically-relevant compounds, several of which were recently published in the Journal of Biomolecular Screening. I have recently moved to Wayne State University as Assistant Professor of Pediatrics where I continue to collaborate with the CCG on several projects related to the primary screen."  Contact Andrew Fribley by email. 

 

CCG Logo
The Center for Chemical Genomics (CCG) assists researchers in carrying out high-throughput screens of chemical and siRNA libraries to identify new tools for biological research.  The CCG also provides access to MScreen, an open-source, high-throughput (HTS) data storage and analysis system.

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Upcoming CCG Events  

CCG User Forum 

 

Wednesday, February 15  1:00-2:00 p.m.

LSI Library, Room #3040  

"Enzo Life Sciences Focused Compound Libraries: Tools to Streamline Targeted Screening"

 by Randy Strube, Ph.D.

Enzo Life Sciences 

 

Host:  Tonia Buchholz 

 
Funding Opportunities
New Screening Opportunities from the NIH:

If you are thinking about submitting for the June deadline, please notify CCG staff now.

PAR-12-058 Solicitation of Assays for HTS to Discover Chemical Probes (R01)

PAR-12-059 Solicitation of Assays for HTS to Discover Chemical Probes (R21)

PAR-12-060 Solicitation of Assays for HTS to Discover Chemical Probes (R01)

CCG in the News
Read about the HTS Core's use of TTP Labtech's mosquito X1 instrumentation in "Screening Large Compound Libraries" Genetic Engineering & Biotechnology News, Feb 1, 2012 issue: "Using mosquito X1, the group has successfully increased its screening capability to 3,000 compounds in a single run (from 200 compounds)."
CCG-Related Publications
Grembecka J et al. (2012) Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia. Nat Chem Biol Jan 29. doi: 10.1038/nchembio.773. [Epub ahead of print]. PubMedLink

Sun H et al. (2012) Inhibitor of streptokinase gene expression improves survival after group A streptococcus infection in mice. doi: 10.1073/pnas.1201031109

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