With longstanding interests in the chemical etiology of human disease, the current research program in the Dedon Lab emphasizes the chemical biology of RNA and DNA modifications in microbial pathogenesis and human cancer biology, bridged by a common theme of chemical immunology and inflammation. The research group recently discovered phosphorothioate modifications in bacterial genomes, including the human microbiome, with these DNA modifications conferring resistance to oxidative stress and present in bacteria of human gut microbiome. In collaboration with Tom Begley, his group used a systems-level analysis to discover a mechanism of translational control of cell response involving reprogramming of tRNA modifications and selective translation of codon-biased mRNAs for stress response proteins. This second genetic code and translational response mechanism has now been observed in eukaryotes, prokaryotes and even RNA viruses, with the discovery of a novel tumor suppressor mechanism and pathways controlling bacterial dormancy. Collaborations on translational control mechanisms with Julien Lescar and Thomas Dick in Singapore have led to new structure- and screening-based drug development projects. The Dedon Lab currently collaborates with New England Biolabs in DNA modification discovery, Novartis Institute for Tropical Disease in dengue virus biology, Wuhan and Jiao Tong Universities in China in phosphorothioate chemical biology, NUS, Duke-NUS and NTU in Singapore in Pseudomonas, malaria, tuberculosis, dengue biology and drug development, and the Universities of Albany and Florida in mechanisms of translational control of cell response.
The current research program has four broad projects: