The work described in this proposal will help me explore a fundamentally new direction and significantly broaden my intellectual perspectives and my technical repertoire. I propose to shift my intellectual focus from the evolution of animal development to the evolution of human disease. In so doing I will augment my technical expertise in molecular biology (primarily working with DNA) with new approaches rooted in cell biology (primarily working with proteins - another of the fundamental biological macromolecules). The initial case will be to begin to understand the evolutionary and functional origins of the molecules, APP and BACE, underlying Alzheimer's Disease (AD). In order to test my current hypothesis about the functional timing of the origin of these molecules, I first need to learn how to do functional work with normal human APP and BACE proteins. This is the main thrust of the proposal and will be done in collaboration with my colleague Dr. Blaine Moore. In order to continue along this line of research, I also wish to establish longer-term collaborations with mainstream AD researchers by attending a national Cell Biology conference. Successful completion of this project should allow me to solidify this new research direction, produce a publication, provide critical background for a grant to the NIH, and establish new research collaborations.