CCG Newsletter
News from the CCG:

February 2013
In This Issue
Research Highlight
Funding Opportunities
Upcoming Events
Publication Highlight
Other CCG-Related Publications
CCG Leadership Announcement
Research Highlight - Interview with Tomasz Cierpicki
Tomek Cierpicki, Assistant Professor, Department of Pathology, UM Medical School   Cierpicki Head Shot
Where did you train?  I graduated from Wroclaw University in Poland and did my postdoctoral research working simultaneously in two laboratories at the University of Virginia with Dr. Zygmunt Derewenda and Dr. John Bushweller. This was a perfect combination because I was applying both the macromolecular X-ray crystallography and biomolecular NMR in my research projects. At this time I learned modern science has to be interdisciplinary. While working in Dr. Bushweller's lab, I became fascinated about how much we can learn about molecular mechanisms of cancer using biophysical and structural biology studies. This research experience had a very strong impact on my current research interest.
How long have you been at UM?  I joined the Department of Pathology at the University of Michigan in 2009 as an Assistant Professor.
What are your research interests?  I am interested in understanding protein-protein interactions which are relevant to the development of cancer. Having this understanding we could develop small molecule inhibitors to block the function of these proteins. My current research is focused on structure-function studies of protein-protein interactions important in leukemia and in finding small molecule inhibitors targeting these interactions.

What are you working on now with the CCG?  One of the projects in my lab is focusing on identification of inhibitors of CDC25 phosphatases. Despite over two decades of efforts to inhibit these phosphatases, there are currently no validated non-covalent inhibitors of CDC25s. We plan to change this by applying an innovative approach to target the protein-protein interactions instead of inhibiting phosphatase catalytic activity. What I like in particular about CCG is that once you have an idea you can contact CCG and immediately start screening for active compounds

What is fragment screening?  Fragment screening is a concept of using small libraries of diverse and relatively simple small molecules (we call them fragments) to identify ligands, which bind to protein target. The fragment library typically consists of 1000-3000 compounds with low molecular weights (e.g. below 250Da), which represent many different scaffolds enabling great exploration of chemical diversity. Although they will be lower affinity binding, fragments have a higher probability than HTS hits of matching a protein-binding site and are easier to modify to achieve high affinity and selectivity. The goal of fragment screening is to identify initial ligands which can be further optimized using medicinal chemistry to rationally develop potent inhibitors with desired properties.
Why is it useful - don't we really want compounds that affect activity?  We obviously want compounds that affect activity! However, there is no guarantee that such compounds are present in the HTS library for our target. Starting from fragments, we can access much larger chemical space than available in HTS libraries. The fragment screening approach is particularly suitable for challenging systems such as protein-protein interactions, where identification of small molecule inhibitors using classical approaches, such as HTS, may be very difficult.
What resources are available at UM to undertake fragment screening?
  Fragment screening requires a suitable library of small molecules and appropriate analytical methodology for detecting the binding with high sensitivity. At UM we have excellent tools for fragment screening such as NMR or surface plasmon resonance (SPR) as detection methods. I am a big supporter of employing protein-detected NMR experiments for fragment screening. In the Department of Pathology, we have a Bruker 600 MHz spectrometer equipped in cryogenic probe and automated sample changer, which is perfectly suitable for fragment screening. Using this instrument we can screen a library of 1000 compounds in less than a week. For screening purposes, we have two fragment libraries: Maybridge library of 1000 compounds available in my lab and Asinex library of ~2,600 compounds with natural product-like features recently acquired by CCG. Both of these libraries are available for UM researchers. 

How can NMR help investigators discover or improve chemical probes?  NMR is a powerful method that can be used in multiple stages of chemical probe development. First, NMR is a label-free method which verifies whether small molecules bind directly to protein target in solution. Then, NMR can be used to accurately map the binding site for small molecules on the protein. Furthermore, NMR spectra also tell us a lot about the behavior of small molecules in aqueous solution, like aggregation, stability, concentration etc. Finally, NMR is a relatively straightforward method and is fun to use!

 In what cases is NMR the best approach for discovering new compounds?  NMR-based screening may be used for two main purposes: to identify fragment-like molecules for further optimization or to assess "ligandability" of protein target (a potential of protein to bind small molecules). The use of NMR for discovering new compounds is particularly useful in case no biochemical or binding assay is available. Also, NMR screening offers a powerful alternative to HTS, especially in cases where HTS yielded no satisfactory hits. We just need to keep in mind that hits identified from fragment libraries need further work and optimization using medicinal chemistry.

Funding Opportunities

Internal Funding Opportunities:
CDNM Pilot & Seed Grant applications for Advancing Drug Discovery are due February 15, 2013.
Click here for more information.

Funds are available for members of the Michigan Diabetes Research Training Center (MDRTC) to conduct RNAi and small molecule screens.  Click here for more information.

The Nathan Shock Center for the Biology of Aging has funds for UM researchers to utilize the university Cores.  Click here for more information.

External Funding Opportunities: 
Drug Discovery for Nervous System Disorders (R01)


Drug Discovery for Nervous System Disorders (R21)


Functional Epigenomics: Developing Tools and Technologies for Cell-type, Temporal or Locus-specific Manipulation of the Epigenome (R01)


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


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


Solicitation of Validated Hits for the Discovery of in vivo Chemical Probes

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 Events  

CDNM Lecture Series

February 22, 2013   

Timothy R. Hughes, Ph.D., Professor, Banting and Best Department of Medical Research, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto 


"Exploring the Eukaryotic Protein-Nucleic Acid Interactome"   


9:00-10:00 a.m., Forum Hall, Palmer Commons

Host:  Jason Gestwicki 


Additional information about the CDNM Lecture Series can be found on its website: 
Publication Highlight
Published online February 10, 2013 in Nature Medicine:
Reilly, Shannon M. et al. and An Inhibitor of the protein kinases TBK1 and IKKE improves obesity-related metabolic dysfunctions in mice.
Other CCG-Related Publications
Larsen, MJ et al. Functional Expression and Characterization of the C. elegans G-protein-coupled FLP-2 Receptor (T19F4.1) in Mammalian Cells and Yeast. Intl J Parasit: Drugs and Drug Resistance 3 (2013) 1-7.


Warner, N et al. A Genome-Wide siRNA Screen Reveals Positive and Negative Regulators of the NOD2 and NF-kB Signaling Pathways. Sci Signal, 2013 Jan 15;6(258):rs3. doi: 10.1126/scisignal.2003305.  PubMed Link


Majmudar CY, et al. Sekikaic acid and lobaric acid target a dynamic interface of the coactivator CBP/p300. Angew Chem Int Ed Engl, 2012 Nov 5;51(45):11258-62. doi: 10.1002/anie.201206815. Epub 2012 Oct 8.   PubMed Link

More CCG-related pubs  
CCG Leadership Announcement
David Sherman is interim Director of the Center for Chemical Genomics.
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