The overall project goal is to achieve system-level intelligence of the sulfotransferase (SULT) 1A gene family that has expanded in primates and been linked to drug metabolism, cancer, hormone regulation, and neurotransmitter biology. The goal will be accomplished by applying bioinformatic and experimental methods in studying the evolutionary history, transcriptional regulation, and protein network of the family. These studies will immediately benefit efforts to exploit inter-individual genetic variation in offering genetically tailored medicine. This project will also enable higher-level modeling of the system in the future that should yield practical therapeutic solutions for repressing the ill-effects of sulfonation, which is currently a paralyzing issue in the field.
The specific aims of this work are 1) to examine the family's evolutionary model in a phylogenomics context and detect episodes of functional change and conservation with statistical tests, 2) to model the regulatory controls of human SULT 1A gene expression, and 3) to determine novel protein interactions involving the human SULT 1A enzymes. While pursuing these aims the applicant will engage in laboratory meetings and attend seminars and selected course lectures on areas related to his training at the University of Florida. ? ?
