Core B has continuously served all projects of the PPG for the past 23 years. The roles of this core are divided into two divisions. Division I oversees the acquisition, breeding and maintenance of mice colonies, the predominant species used for this project. It will also breed new inducible transgenic mouse strains using the Cre-Lox system to produce cell specific gene modifications that are optimally suited to address the aims ofthe various projects. Division I will also provide freshly dispersed cells for investigators as well as cultured cells and tissues. The PPG has been extremely fortunate to have a long standing arrangement with Charies River Laboratories which provides us with gastrointestinal muscles from the Cynomolgus monkey. Core B is responsible for the acquisition and distribution of these tissues to investigators as well obtaining muscle samples from patients undergoing surgery for diseases of the colon. The role of Division II is to oversee the flow cytometry activities of Core B. This division has been extremely successful in using flow activated cell sorting (FACS) to separate and analyze select populations of cells isolated from the tunica muscularis. The acquisition of transgenic mice expressing GFP in smooth muscle cells (smMHCCre-egfp), ICC (KitcopGFP/-!-) or PDGFRa+ cells (PDGFRa-egfp/+) has further advanced our ability to sort and analyze highly pure populations of cells in sufficient quantities to create high resolution gene expression profiles on a genome-wide scale. Generating these cell specific transcriptomes will allow investigators to compare gene expression in different cell types and within a given cell type with development or during a pathological condition such as partial obstruction. In summary. Core B is an indispensable and highly successful component ofthe PPG that continues to grow and diversify as new methodologies and approaches become available.
This study will provide important new information with regard to how motility in the intestine is controlled. Although gastrointestinal disorders usually do not kill patients they result in enormous pain and suffering. The treatments available are rarely sufficient and require billions of health care dollars. The studies described here are highly innovative and will aid in developing new treatments for Gl disorders.
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