Grant: Discovery Grants Program - Individual

Proteomics plays an increasingly important role in bioscience and biomedical research, such as in the discovery of potential protein biomarkers for disease diagnosis or prognosis. However, current analytical techniques only detect a small portion of the proteome from a cell or tissue sample. While the analysis of a partial proteome is sufficient for some biological applications, large scale biological studies, such as systems biology and disease biomarker discovery, require a comprehensive analysis of the proteome. Thus the main objective of our research is to develop advanced mass spectrometric techniques for proteome analysis with an ultimate goal of analyzing the entire proteome of a cell or tissue at high speed, i.e., whole proteome profiling. To achieve our goal, we will develop analytical tools for high resolution protein fractionation, efficient protein digestion, multidimensional liquid chromatography separation of peptides, effective tandem mass spectrometric sequencing of peptides, and high confidence database search for protein identification. We will apply each developing technique to real world samples, such as E. coli, yeast, human cell lines or tissue samples, to gauge its analytical performance and illustrate the practical utility of the method. We will also investigate the operational mechanism of each method so to further optimize its analytical performance. In the end, we will integrate these methods to develop an analytical platform that will enable whole proteome profiling with high efficiency and specificity. The expected significance of this research includes the development of new mass spectrometric techniques and methods for comprehensive proteome profiling and the demonstration of these methods for whole proteome profiling of several types of important biological cells. This research also allows the training of a number of highly skilled and highly sought-after analytical chemists.