PROTEIN-BASED HEREDITY IN BACTERIA

With a primary emphasis on bacterial genetics, our laboratory uses bacteria to study prions and protein-based heredity. Prions are infectious, self-propagating protein aggregates (typically amyloid) that are notorious for causing devastating neurodegenerative diseases in mammals. They have also been described in fungi, where they act as protein-based hereditary elements. Despite the apparent conservation of prion-forming proteins in evolutionarily divergent members of the fungal Kingdom, it was not known whether such proteins exist in bacteria. Our prion work was initiated to investigate this possibility. Having first demonstrated that E. coli cells have the requisite molecular machinery to propagate a model yeast prion, we subsequently uncovered several bacterial prion-forming proteins. At the same time, we have developed a set of genetic tools for detecting the conformational transitions that are diagnostic of prion formation. The identification of bacterial prion-forming proteins points to a previously unrecognized source of phenotypic heterogeneity in bacteria. Ongoing work is directed at investigating the physiological impacts of bacterial prions, the cellular determinants of prion formation and propagation, the sequence and structural determinants of heritable amyloid, and the scope of prion-like phenomena in bacteria.

TRANSLATIONAL FRAMESHIFTING

A second set of projects in the lab centers on translational fidelity and non-programmed ribosomal frameshifting. More specifically, having uncovered instances of an unexpectedly high basal level of ribosomal frameshifting in bacteria, we are investigating the mechanistic underpinnings of these events and their physiological implications.