Structure and Specificity of Restriction-Modification (R-M) Systems

Project Summary/Abstract This application is a request for a Diversity Supplement to train and support a talented PhD student, Mr. Richard Quintana-Feliciano, to complement our parent grant (NIGMS R35-GM131780), titled “Structure and specificity of restriction-modification (R-M) systems”. As a Hispanic first-generation student, and coming from a low socioeconomic status, Richard has strived to excel at every step of his academic preparation, and has shown the ability and motivation to contribute fundamentally to the goals of the parent grant. The theme of the parent grant is the study of R-M systems that comprise the innate immune system in bacteria and archaea. A new paradigm in the in R-M field is the co-option of orphan and R-M methyltransferases in bacteria for epigenomic regulation of genes that are often associated with virulence factors. Richard proposes to study DNA methyltransferases (BCAM09902 and BCAL3494) from B.cenocepacia that regulate the bacterium’s biofilm formation or motility, as an extension of the parent grant. The research training is designed to bring him to a stage where he can take a problem from its infancy to an atomic crystal structure, with an understanding of the underlying thermodynamics and kinetics. The training plan has additional important elements, including specific courses and directed reading, participation in seminars and meetings, and an advisory committee to monitor and guide his progress. The expectation from this comprehensive training plan is that he will be able to successfully defend an outstanding PhD thesis, publish papers in a top tier journal(s), and also write a postdoctoral fellowship application for the next stage of his career in developing as an independent academic investigator.