About Us - Framework
Many of the goals of the Consortium are non-hypothesis based, with the objective of producing reagents, technologies and databases for use by the migration community as well as deriving tools and data for integrative and interactive modeling efforts. The Consortium has established Development Initiatives to address specific barriers to research. These Initiatives bring together researchers with the critical expertise needed to address the Initiative objectives.
Joan Brugge, Benny Geiger, Denise Montell, Jean Schwarzbauer, Ron Vale
Objective: The overall goal of this Initiative is to expand the current Migration Knowledgebase through the identification of cellular genes that regulate cell shape, adhesion and motility using high throughput RNA interference screens in cell- or organism-based assays. In addition, large scale expression screens will be employed in the fruit fly to identify candidate genes that display patterns of expression and intracellular localization consistent with a role in migration. Through coordinated cross-species analyses we will identify a set of genes that play a central and conserved role in cell adhesion and migration.
Mark Ginsberg, J. Thomas Parsons, Jay Fox, Donald Hunt, Richard Klemke, Rick Horwitz
Objective: The overall goal of the Proteomics Initiative is to use mass spectrometry based proteomics methods to expand the current Migration Knowledge database by 1) examining phosphorylation site utilization on proteins that regulate cell motility, 2) further developing methods for measuring differential phosphorylation of those proteins, and 3) using quantitative methods to assess positional and kinetic variation in phosphorylation site utilization in migration-related proteins. In addition, the Initiative will extend these methods to tissue using transgenic methods.
Robert Liddington, Iain Campbell, David Critchley, Dorit Hanein, Kenneth Taylor, Neils Volkmann
Objective: The overall goal of this Initiative is to determine the high resolution structures of two major migration organelles: adhesions and protrusions. Our approach is to combine structural methods that range from correlative light and high resolution electron microscopy to X-ray and NMR. As part of this effort, we are developing a new imaging concept that allows us to capture by light microscopy the spatial-temporal aspects of migration in living cells and to visualize the same structures using high resolution electron microscopy. High resolution structures of individual proteins and their detailed interactions with binding partners obtained by NMR, X-ray or tomography (“bottom up approaches”) can then be computationally docked into three-dimensional maps of the complexes.
Martin Schwartz, Klaus Hahn, Barbara Imperiali, Stephen Sligar
Objective: The goals for the Biosensor Initiative are to continue to develop biosensors for key regulatory and effector nodes in cell migration and to use existing and proposed biosensors to acquire quantitative data that can be used to develop and experimentally verify theoretical models of cell migration. A major focus will be Rho family regulators as they control key migration nodes. In addition the Initiative will focus on the construction of biosensors and photoactivatable reagents, using both existing and new technologies, for key upstream and downstream members of these signaling pathways. The long term goal is to produce a detailed experimental and mathematical analysis of a specific, critical signaling pathway in cell migration.
Alex Mogilner, Gaudenz Danuser, Linda Griffith, Jason Haugh, Doug Lauffenburger, Leslie Loew
Objective: The Modeling Initiative is constructing a variety of different models both relational and biophysical of the mechanics and regulatory phenomena related to cell migration. These models are being implemented in the publicly available Virtual Cell (VC) modeling platform. The long term goal is the in silico reconstitution of a simplified motile system. Our approach uses mathematical representation combining biological knowledge and hypotheses, with determination of the consequences of these hypotheses facilitated by computer-generated numerical calculations. The models will be standardized from the technical point of view, integrated, comprehensive and predictive. A crucial feature of our endeavor is that all modeling is undertaken with experimental collaborators.
Imaging & Photomanipulation Initiative
Kenneth Jacobson, John Condeelis, Enrico Gratton, Rick Horwitz, Barbara Imperiali, Manfred Radmacher, Paul Wiseman, Claire Brown
Objective: The goal of the Imaging and Photomanipulation Initiative (I&PI) is to develop technologies for measuring and perturbing the localized activities that mediate and regulate cell migration and to use these technologies to make quantitative measurements useful for modeling cell migration. The emerging experimental paradigm is to initially detect and quantify local molecular events in migrating cells and then to manipulate these events by local activation or inactivation and assess the consequences on migratory processes. In addition to developing technologies, we will also use them on prototypical migration phenomena to develop working paradigms for studying cellular processes that are tightly regulated both spatially and temporally.
William Pearson, Lincoln Stein
Objective: Consortium activities are supported by two kinds of Bioinformatics support: Information Dissemination and Information Coordination. The goal of the former is to disseminate information on technology, scientific findings and methodologies in a rapid, yet responsible manner. The goal of the latter is to provide hardware and software infrastructure to manage, analyze, and distribute the sequence, expression, and structural information as well as information on Cell Migration activities, produced by the Cell Migration Consortium. The Cell Migration Gateway is the major forum for information transfer. The Gateway includes bibliographies, reviews of new publications, and information relevant to the broader migration community. The site includes data, technologies, reagents, and other products of the Consortium as well as detailed descriptions of Consortium activities and approaches for each initiative. Information on data release and collaboration policies, lists of completed, ongoing and planned activities, and contact personnel are also provided. Finally, there are lists of pertinent, non Consortium generated resources.
Transgenic & Knockout Mice
Objective: The goal is to produce transgenic and knockout mice and the cell lines derived from them for various Consortium activities. These activities are now incorporated into the specific initiatives with which they interact; however all mice and cell lines developed by the Consortium are posted on the Consortium website and available to the Community.
Objective: As a part of its activities, the Consortium is generating materials that may be useful for others. These efforts are integrated into the initiatives that need them. The methods for generating the biomaterials that we use are presented on the Consortium web site.