The reversible binding of proteins to cellular membranes is central to many biological processes and is often accomplished through lipid-interacting protein domains. The Arabidopsis genome contains at least 2,000 such domains. Different types of lipid signals target the domains to different cellular membranes. The interaction of lipid-binding domains with membrane surfaces is an essential part of their function. This project aims to understand, at the molecular level, how these domains are recruited to different cellular membranes and how proteins and lipid signals are organized laterally at membrane surfaces and, thus, regulate cellular processes. Function will be determined at the family and genome levels through the synthesis of computational and experimental analyses. An automated high-throughput comparative modeling pipeline will detect new instances of lipid-binding domains in the Arabidopsis genome and predict the structures of their amino acid sequences using known structures as templates. The biophysical properties of these models will be calculated and the functional predictions will be tested through the interpretation and rational design of experiments. Ultimately, detailed models of the physical interactions underlying lipid signaling pathways at membrane surfaces will be built in collaboration with experiment. This project reflects all three of the current 2010 Project focus activities: 1) Benchmarking gene function. Genes from Arabidopsis will be quantitatively compared with genes from other, much more annotated model organisms. 2) Developing genome-wide tools for analyzing gene function: The comparative modeling pipeline, which is highly modular, is the framework for a comprehensive tool that allows for the inclusion of new computational methods to facilitate both larger scale and more detailed annotation of gene function. 3) Exploring exemplary networks and systems: The results for individual lipid-binding domains will be leveraged to model how proteins and lipids collaborate to transduce cellular signaling. Finally, an automated mechanism for alerting other 2010 Program groups to potentially useful results will be implemented. Information on this project is posted at http://maat.med.cornell.edu/Arabidopsis2010/arabidopsis2010.html.
The foundation of this effort is a strong partnership between Weill Medical College of Cornell University (WMC) and City University of New York Brooklyn College (CB), which is a non-PhD granting institution. The values of this partnership are research, education, mentoring, and outreach activities. Through this project, two early career female scientists, one of which has two children, will receive training in new areas of biology and computation and, together, will develop a supportive research environment for women through this project as well as other areas of research. Both labs mentor many young women at all levels of education, from high school through the postdoctoral level. There is strong multidisciplinary and multiethnic student participation: Two minority female high school students were finalists in the International Intel Competition, and another minority female high school student is currently working on an Intel project. Undergraduate and graduate students at CB and WMC are being trained in computational biology by participating in this project and through formal course work. Both investigators design and teach classes in Bioinformatics, Computational Biology, Biochemistry, Logic and Critical Analysis, and journal-based "Focus Groups". The results of this project will be broadly disseminated through 1) a dedicated, publicly accessible, database-driven website with links to online Arabidopsis resources; 2) participation in multi-disciplinary conferences and Arabidopsis-specific data-support services; 3) publications in quality, multidisciplinary journals, e.g. PLoS Computational Biology, which seeks to make computation accessible to biologists; and 4) seminars presented to "Women in Science" programs and programs meant to recruit students from other fields into biology, e.g. American Physical Society Biology Tutorials. It is anticipated that a highly successful, eight-session, 48-speaker symposium on protein/membrane interactions, organized by one of the investigators for the American Chemical Society March 2006 meeting, is the first in a series of similar meetings that will bring together experimental and computational researchers in this field. Future meetings will have sessions devoted to Arabidopsis membrane binding proteins.
