The Cell Migration Consortium
Migration is a pivotal process in many diverse phenomena including embryonic development, tumor formation and spread, leukocyte recruitment during immune responses, and wound repair. Elucidating the mechanisms underlying cell migration presents a formidable intellectual challenge since it is comprised of several complex molecular and cellular processes that must be coordinated in both space and time. A full comprehension of the process of cell migration requires an interdisciplinary approach that combines diverse specialists with skills to bring novel technical and intellectual solutions to the problem. While migration research is undergoing rapid growth in both investigators and knowledge, progress will soon by restrained by an approaching set of intellectual and technological barriers. At the center of the Cell Migration Consortium is a highly interactive, multi-disciplinary research initiative comprised of Core Investigators with outstanding records of accomplishment in the field of adhesion and cell migration, collaborators who bring needed technology and expertise from other disciplines, e.g., mathematical modeling structure, imaging, biomaterials, and are supported to apply their expertise to the migration problem. A major objective of the Consortium is to develop new technologies that are needed to overcome the barriers that face cell migration research. This is being accomplished by supporting five innovative, research initiatives under the direction of core investigators. The Proteomics and Genomics Initiative is determining the complete repertoire of genes and gene products that contribute to cell migration; the Structure Initiative is analyzing the organization of large, supra-molecular adhesive assemblies at the macro and atomic level, the Signaling Initiative is seeking novel approaches to the detection of activated states of signaling molecules in space and time; the Transgenic and Knockout Initiative is creating cells and mouse models with genetically altered migration machinery; the Modeling Core is developing quantitative assays and modeling mechanisms of component migratory processes and signal transduction through networks. In addition, the Consortium supports critical technologies and technology development through key Support Facilities, including mass spectrometry, biomaterials, protein production and analysis and cell imaging. Finally, the Consortium is providing infrastructure to support the administrative needs of the Consortium, promote interaction through video telecommunications, bioinformatics, data and information dissemination and the technology resources that are common to all of the Consortium projects.
Inflammation and the Host Response to Injury
The host response to trauma and burns is a collection of biological and pathological processes that depends critically upon the regulation of the human immuno-inflammatory response. No single research center or small group of centers has the resources to delineate the integrated response of this complex biological system, which involves multiple molecular and genetic interactions that vary in time. Our program promotes the identification of important dynamic relationships that regulate the integration of this complex biological system, with the expectation that this understanding will ultimately impact the treatment of hospitalized patients. For the first time, our large-scale collaborative program provides the means to acquire necessary new knowledge - knowledge acquired using highly complex databases and very diverse technologies - to achieve the overall scientific goal of defining the multi-level control mechanisms and their integration in the patient's trauma-induced immuno-inflammatory response. The program has successfully integrated multiple key investigators who have not traditionally been involved in trauma research, including biologists who are leaders in genome-wide expression analysis, engineers who are well-recognized in computational analysis for the understanding of genome-wide studies, and bioinformatics experts who are leaders in the construction and analysis of large, complex, relational databases. The investigator-group has worked well together to expand the traditional, hypothesis-driven mechanistic approach to understand the immuno-inflammatory host response to a discovery-driven approach. The novelty and uniqueness that our program brings is in the application of genome-wide expression analyses and proteome-wide surveys of plasma and leukocyte populations to class prediction and the mechanistic biology of inflammation, trauma, and burns. The program has a strong commitment to share the data, protocols and case report forms as products of our research with the broader scientific community.