The making and breaking of adhesive contacts play major roles in embryonic development and in spread of cancer. This laboratory has been continuously funded for over 2 decades by about $4 million in research and science infrastructure grants with present active funding at $2 million. Currently, the cell adhesion projects described below are supported by about $170,000 of available, ongoing funding. Over 175 student co-authors appear on cell adhesion publications from this lab and recent minority students who have held NIH, DOE and NASA fellowships in the lab are now in Ph.D., MD/Ph.D. and research MD programs in cell, developmental biology and biochemistry at Harvard, university of Iowa, Stanford and university of California, Berkeley. This application is therefore for Associate status. Current MBRS students, as well as new ones, in addition to MARC, MAERC and Howard Huges minority fellows in the lab, will work on the following ongoing projects: (1) Determination of specific molecular groups involved in a specific morphogenetically important cellular adhesive interaction in living sea urchin embryos, by probing this interaction with molecules that mask specific cell surface receptors, enzymes that degrade them and molecules that compete for their binding sites. (2) Identification of which protein bands are responsible for promoting species-specific an developmentally stage-specific sea urchin cell reaggregation using polyacrylamide gel electrophoresis and the technique of Western cell adhesion. (3) Identify what chemical groups, when isolated from all others in a model system, can make adhesive bonds stable enough to hold cells together. This is accomplished using derivatized agarose beads that enable the investigator to test over 20,000 molecular combinations. Although many cell adhesion molecules have been discovered, very little is known about the types of bond involved in adhesive interactions. In some cases specific peptides, such as arg-gly-asp and his-ala-val, or specific carbohydrates have been implicated in the binding of these molecules, but much is still to be learned about the actual molecular groups that are responsible for forming adhesive bonds between cells. MBRS students are involved in entirely new approaches to solve cell adhesion problems that have never been used before. Introduction, for example, of the use of derivatized beads in our most recent papers, receiving unusually large numbers of reprint requests, is entirely new.
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