The Wisconsin Center of Excellence in Genomics Science (CEGS), which was established in 2009 as a collaborative effort between researchers at the Medical College of Wisconsin and the University of Wisconsin Madison, has been awarded a $6.2 million grant extension from the National Institutes of Health’s National Human Genome Research Institute (NHGRI). The grant provides an additional two years of funding to the CEGS, which is one of only ten Centers of Excellence in Genomic Science supported by NHGRI. The award followed the recommendations of a panel of expert reviewers that evaluated the progress the Center had made during the initial two years.
The Center, co-directed by Michael Olivier, Ph.D., professor of physiology at the Medical College’s Biotechnology and Bioengineering Center (BBC) and the Human and Molecular Genetics Center (HMGC) and Lloyd M. Smith, Ph.D., W.L. Hubbell professor of chemistry and Director of the Genome Center of Wisconsin at UW-Madison, has developed a new technology, called GENECAPP, which allows the characterization of proteins bound to specific regions of the DNA in cells. Instead of the traditional approach of identifying the DNA sequences where regulatory factors bind, these researchers are developing novel technologies that identify the proteins that bind to particular DNA regions. Through this approach, the team may identify entirely new regulatory proteins. The initial groundbreaking work was recently published in PLoS One. “Our ultimate goal is to develop this unique technology into a tool that can be used to better understand how the human genome and its genes are regulated by proteins. So far, we have been able to demonstrate the feasibility of our novel approach, but the crucial next step will be to improve it so that it can become a reliable and robust tool for the biomedical research community,” said Michael Olivier.
The newly awarded funds will allow the Wisconsin CEGS to advance its groundbreaking technology and apply it to pressing biomedical questions to help understand gene regulation in general, and specific challenges such as the mechanisms underlying virus infections and drug resistance in cancer cells.
For questions or more information on the Wisconsin Center of Excellence, please visit the Center website at http://www.wisconsincegs.org, or contact Theresa Lins (tlins@mcw.edu), the Center coordinator.
Sequence-Specific Capture of Protein-DNA Complexes for Mass Spectrometric Protein Identification
The regulation of gene transcription is fundamental to the existence of complex multicellular organisms such as humans. Although it is widely recognized that much of gene regulation is controlled by gene-specific protein-DNA interactions, there presently exists little in the way of tools to identify proteins that interact with the genome at locations of interest. We have developed a novel strategy to address this problem, which we refer to as GENECAPP, for Global ExoNuclease-based Enrichment of Chromatin-Associated Proteins for Proteomics. In this approach, formaldehyde cross-linking is employed to covalently link DNA to its associated proteins; subsequent fragmentation of the DNA, followed by exonuclease digestion, produces a single-stranded region of the DNA that enables sequence-specific hybridization capture of the protein-DNA complex on a solid support. Mass spectrometric (MS) analysis of the captured proteins is then used for their identification and/or quantification. We show here the development and optimization of GENECAPP for an in vitro model system, comprised of the murine insulin-like growth factor-binding protein 1 (IGFBP1) promoter region and FoxO1, a member of the forkhead rhabdomyosarcoma (FoxO) subfamily of transcription factors, which binds specifically to the IGFBP1 promoter. This novel strategy provides a powerful tool for studies of protein-DNA and protein-protein interactions. Read more here.
The latest issue of International Innovation features an article on the Wisconsin Center of Excellence in Genomics Science (WI CEGS). The article can be found here.
March 24 1:30 pm, Biotechnology Center Auditorium, 425 Henry Mall Presentation by Gary Stormo (Professor, Genetics, Washington University School of Medicine), Title TBA
The Wisconsin Center of Excellence in Genomics Science is pleased to announce its Advisory Board members. This Advisory Board is made up of external members as well as advisors with in-depth knowledge of the Center’s research. The Advisory Board plays a key role in evaluating the work of the Center. The Advisory Board will meet with Center faculty and researchers this fall to review the work done thus far and make suggestions on future directions, changes and potential alternative approaches.
External Advisory Board Members:
Neil Kelleher, Ph.D. Professor Director, Proteomics Center of Excellence Northwestern University Evanston, IL Dr. Kelleher’s laboratory has three main areas of research: custom instrumentation for Fourier Transform Mass Spectrometry (FTMS), Nuclear Signaling and Natural Products. More specifically, the lab’s main interests lie in the enzymology of natural product biosynthesis, mass spectrometric-based studies of the “Histone-Code,” and development of FTMS for Top Down Proteomics (i.e. analyzing intact proteins directly; no proteases).
Richard Myers, Ph.D. President, Director and Investigator HudsonAlpha Institute for Biotechnology Huntsville, AL Dr. Myer’s research focuses on molecular basis of human inherited diseases and traits, including Huntington disease, Parkinson disease, bipolar disease, cancer, atherosclerosis, resistance to infectious agents, and differential responses to environmental assaults; Human population genetics;Functional genomics, including genome-scale analysis of cis-acting sequences, DNA binding proteins and epigenetic action involved in human gene regulation; Genomic basis of vertebrate diversity.
Robert Deschenes, Ph.D. Professor and Chair of Molecular Medicine< br/> University of South Florida Tampa, FL Dr. Deschenes’ research group and collaborators are currently focused in two general areas. The first deals with the posttranslational modification and the subcellular localization of cancer signal transduction proteins. The second deals with stress signaling and the characterization of histidine kinases.
David Mitchell, Ph.D. Assistant Professor University of South Florida Tampa, FL Dr. Mitchell’s research addresses and understands some of the complex molecular signal transduction mechanisms in nature using the model organism, Saccharomyces cerevisiae. He is focusing on two research objectives: a) understanding the complex interplay between cellular membranes and proteins that are peripherally associated with these membranes and b) characterizing the factors which regulate Palmitoyl Acyl Transferases (PAT), an enzyme that posttranslationally attaches long chain fatty acids to proteins.
A team of Wisconsin researchers from the Medical College of Wisconsin, University of Wisconsin-Madison and Marquette University will receive $8 million from the National Institutes of Health to develop technology that provides new ways to study genes.
The funding will go to the newly-established Wisconsin Center of Excellence in Genomics Science to support this collaboration. Read more about this grant in the press releases below.
