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NU-PSOC Announces Pilot Project Awards

July 2010

Northwestern University Physical Sciences-Oncology Center (NU-PSOC) announced the award of its first annual Pilot Project grants. Robert H. Lurie Comprehensive Cancer Center of Northwestern University members, Richard W. Carthew, PhD, Owen L. Coon Professor of Molecular Biology, and Xiaozhong (Alec) Wang, PhD, Assistant Professor of Biochemistry, Molecular Biology, and Cell Biology, were each awarded $100,000 for one year to support their innovative proposals to study genetic control mechanisms in normal and cancer cells. Their projects were selected from a pool of 12 applications based on their scientific merit, novelty and intercalation of the project with the theme of the NU-PSOC: the storage and expression of genetic information in cancer.

Dr. Carthew's proposal, A Quantitative Description of MicroRNA-Transcriptome Interactions, seeks to understand the rules that govern the binding of microRNAs to gene transcripts. MicroRNAs are a recently discovered class of small RNA molecules that can regulate the stability of messenger RNAs (gene transcripts) or the ability of these transcripts to be translated into proteins. MicroRNAs have been found to play an important role in tumorigenesis, with some microRNAs promoting and others suppressing tumor development and metastasis. MicroRNAs thus represent a new and previously unrecognized mechanism of post-transcriptional gene regulation and as such, have evoked enormous interest. Dr. Carthew's study will use state-of-the-art experimental techniques coupled with mathematical modeling to determine binding sites preferences in an animal model, and if successful, this approach can be adapted to the study of human cancer cells. This study is a collaboration between Dr. Carthew and Dr. Sascha Hilgenfeldt, Associate Professor of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign and an expert in mathematical modeling.

Dr. Wang's project, Argonaute-mediated Epigenetic Regulation of Gene Expression in Stem Cells, will explore the novel hypothesis that Argonaute, a protein that forms a complex with small RNAs that is crucial to the ability of these small RNAs to regulate the stability or translatability of gene and transcripts, can also interact with the genes themselves and prevent the production of transcripts from these genes. The proposed regulation of gene expression by Argonaute does not involve any changes in the DNA sequence of the genes and is therefore referred to as "epigenetic regulation." Alterations in the some epigenetic regulation of gene expression are a common feature of cancer cells, and importantly, cancer cells show abnormal levels of the Argonaute protein. Dr. Wang will use an artificially constructed "reporter gene" whose expression is silenced by Argonaute to try to describe how this silencing occurs. Using genetically engineered mouse embryonic stem cells in which the Argonaute protein is present or absent, he will also try to identify DNA sequences with which Argonaute interacts. If results from these studies support Dr. Wang's novel hypothesis, the implications for cancer biology could be very important.

The Pilot Project Program is an important mechanism for fostering collaboration and incorporating new avenues of research into the NU-PSOC. This program is supported by a combination of institutional support and funding from the National Cancer Institute (1U54CA143869. Under the direction of Principal Investigator Dr. Jonathan Widom PhD, the PSOC applies engineering and physical sciences approaches to understanding how information in normal and cancer cells is encoded, decoded, transferred, and translated. The five research arms of the Center variously focus on DNA mechanics, sequence-dependent nucleosome positioning, higher-order chromatin structure, mathematical modeling of epigenetic states, and the regulation of protein degradation. Comprehensive information on the Center's work and mission and additional opportunities for funding research projects through the NU-PSOC are featured on the Center's website.

The product of a partnership between the Northwestern Chemistry of Life Processes Institute and the Lurie Cancer Center, NU- PSOC is one of twelve such centers funded by the National Cancer Institute (NCI) to enable the convergence of the physical sciences with cancer biology in creating new and innovative approaches to better understand and control cancer.

(Last updated on March 10, 2017 )