Lipids present within cell membranes directly control many critical cellular processes, and defects in lipid composition and activity result in a number of debilitating diseases, including cancer and diabetes. A prominent role pertains to protein-lipid binding interactions, in which lipids enforce the recruitment of proteins onto the surfaces of cellular membranes. These processes regulate both protein function and localization, resulting in tight control over numerous physiological processes. Despite this significance, many aspects of protein-lipid binding remain poorly understand due to the inherent challenges of studying events that occur within biological membranes. Herein, comprehensive strategies are proposed to surmount these challenges and unravel the details of these complex binding interactions. One aspect of the proposed research involves the design and synthesis of chemical probes corresponding to important signaling lipids. Here, modular synthetic strategies will be devised for efficient generation of a range of probe structures for use in numerous biological studies. In addition, the Best group will develop novel approaches for characterizing the biological activities of lipids. One such strategy is that of microarray analysis, in which high-throughput techniques employing different formats and conditions will result in rapid detection of the details of membrane binding. In addition to answering important questions about these processes, these platforms will also be used to detect variations in lipid activities between normal and disease-associated systems to study the roles of these compounds in disease. Finally, a probe-based approach will be developed to achieve selective purification and identification of proteins that interact with a particular lipid from complex cell extracts. The Best group will partner with teachers and students at local schools to increase awareness of the merits of scientific research. For example, students from a local high school will perform research in their laboratory and present a poster to showcase their results. In addition, the PI will make presentations at meetings of the school's science academy to inform students about the exciting advancements that result from scientific research. Further, the Best group will partner with local middle school teachers such that graduate students will participate in laboratory courses to enhance these sessions. Through these efforts, they will extend their research to the local community to cultivate a greater understanding of scientific research.
