Frontiers Seminar: Herman Sintim, Purdue University
This event is in the past.
Frontiers Seminar: Herman Sintim, Purdue University (Host: Nguyen)
“Interrupting Cyclic Dinucleotide Signaling in Bacteria and immune Cells with Small Molecules”
The ability of cells to sense and respond to environmental cues is critical for survival. Cells integrate environmental cues to regulate the synthesis and degradation of second messengers, which mediate many essential processes in archaea, eubacteria, and eukaryotes. Cyclic dinucleotides, such as c-di-GMP, c-di-AMP and cGAMP, are newly discovered second messengers in all the three domains of life. In Gram-negative, Gram-positive bacteria and mycobacteria, cyclic dinucleotides orchestrate a dizzying array of processes that include biofilm formation, virulence factors production, cell wall remodeling and antibiotic resistance. Cyclic dinucleotides also affect mammalian cells, particularly immune cells, and play important roles related to inflammation, T-cell maturation and antigen presentation. Due to the essential roles played by these fascinating second molecules, there are now intense research efforts to identify macromolecular targets in the cell that sense these molecules. In the drug discovery arena, efforts have been focused on the identification of small molecules that can perturb cyclic dinucleotide signaling for the potential treatment of various disease states, including viral and bacterial infections as well as cancer. In this talk, I will provide an overview of my group’s contributions to the cyclic dinucleotide field, mainly via a chemical biology approach, and our recent efforts to develop small molecules, which intercept cyclic dinucleotide signaling in bacteria and immune cells.