Grants and Contributions:

Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023)

Phosphorylation is a fundamental mechanism of cellular signalling. The reaction involves a protein kinase (an enzyme that adds a phosphate group to certain amino acids) and a target (substrate) protein. One way to study protein kinases in a high-throughput manner is with kinome microarrays, which consist of hundreds or thousands of probes affixed to a glass slide. After exposure to a prepared sample, all the probes on the microarray are simultaneously measured for evidence of phosphorylation by kinases in the sample, providing a "snapshot" of (potential) cellular phosphorylation activity. Over the past several years, our group has developed various bioinformatics tools to support this technology. We have devised software to help determine the peptides to be used as probes for species-specific or pathway-specific arrays, and software to filter, adjust, visualize, and interrogate the resulting measurements. We have also developed tools for assisting with the evaluation of software for kinome data analysis. With collaborators, we have demonstrated the utility of the technology and software in organisms ranging from plants to insects to humans, with applications ranging from determining an individual's "kinotype" to studying pathogenic mechanisms of Ebola infection. However, the field is still far from mature, with many open questions remaining. The focus of the proposed research program is to address shortcomings of current software supporting kinome microarray technology, to find solutions to known problems, and to develop new, improved algorithms and software tools. Specifically, we will develop improved data normalization techniques, utilize special calibration probes to extract more and better information from the microarrays, and exploit our unique, wide-ranging collection of data to improve kinome microarray technology and to develop software that leads to the discovery of previously unknown signalling pathways.

This research is important to researchers in a broad range of biological sciences, from virology to crop science since cellular signalling is such a fundamental mechanism in cells. Better tools to identify and study signalling networks will facilitate more rapid basic and applied research, and lead to greater biological knowledge. Kinome microarrays are an extremely valuable research tool because they can be employed to study a wide range of biological problems, from human health to agriculture to basic research into cellular physiology. The proposed research will make kinome arrays even more useful for all of these purposes. Another benefit of the proposed program is that it will provide training for undergraduate and graduate students in a highly desirable, inter-disciplinary field (bioinformatics) in which there is a under-supply of HQP (highly-qualified personnel).