Bioinformatics Tools for the Analysis of the Spatiotemporal Organization of Protein Expression in Neural Functional Units
Eduardo Macagno, P.I.
NSF Proposal 0852081

Knowledge of the tissue distribution of essential molecules is necessary for understanding how biological systems function, how they grow, and how they repair themselves following trauma or disease. Proteins and peptides are essential structural and functional elements of the cells and tissues of an organism. During normal development, genetic programs are expressed to provide appropriate levels of thousands of proteins and peptides. These genetic programs shift in order to maintain stable functions in the adult, and some programs are modified or re-expressed if an injury elicits a repair response by the affected tissues. In this project, a multidisciplinary team of investigators will design, test and implement new tools to analyze data obtained by means of the recently developed technique of mass spectrometry imaging applied to the mapping of peptides and proteins in biological tissues. The data sets obtained with this powerful biochemical technique are extremely large. Their analysis and interpretation require novel computational and bioinformatic methods. Application of these new methods will yield detailed maps of the temporal and spatial distributions of thousands of individual molecules and the capacity to examine patterns of expression as well as correlations in expression within ensembles of molecules.

These new methods will be developed and tested first in simple model organisms, to characterize and compare the molecular components in the embryonic, adult and regenerating nervous system. Later, they will be applied in studies of mammalian nervous system slices in order to answer, among other questions, how stem cells are intercalated into and how they mature in adult nervous systems, during normal replacement or artificial replacement following cell loss due to disease or aging. All computational and bioinformatic tools developed in the course of this project will be made available openly to other scientists. It is expected that these tools will be of great interest and will be used by many groups as mass spectrometry imaging becomes more widely adopted. All information acquired through the use of these new tools to analyze nervous system structure and function will be made available through peer-reviewed publication in scientific journals. The project will train a group of scientists at multiple levels, from undergraduates to postdoctoral fellows, in this exciting new area of basic and applied research.

PI: Dr. Eduardo Macagno
coPI: Dr. Vineet Bafna
coPI: Dr. Terry Gaasterland

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