WHAT W E STUDY

Our research is directed at three major areas:

METAEFFECTORS

Effect the unexpected.

A central pillar of molecular pathogenesis is that translocated bacterial effectors modulate host proteins. We have recently uncovered a functionally heretical class of translocated proteins in Legionella pneumophila: "metaeffectors" that target other effectors rather than host proteins. How common are "metaeffectors" across pathogens and how do they shape host-pathogen interactions? To answer these questions, we are using advanced, high-throughput approaches to map hundreds of thousands of genetic and physical interactions across a variety of intracellular pathogens.

CRISPR-CAS

A diary of near misses.

Environmental surveys and laboratory models rarely capture the complexity encountered by pathogens in dynamic real world environments such as municipal water systems, making it difficult to assess risk and develop strategies to mitigate it. Many bacteria, including L. pneumophila, maintain in their CRISPR-Cas arrays a diary of sorts - recording the struggles that they and their ancestors have had to overcome in order to survive. These defences point to frequent encounters with an integrative phage-like element, LME-1, and a class of small phages, gokushoviruses. Together, these studies have led us to identify the best candidates to-date for the ever-elusive Legionella phage.

PATHOGEN EVOLUTION

From pond to patient.

Among all bacterial pathogens studied to date,  L. pneumophila maintains the largest arsenal of effectors, with over 330 effector proteins translocated by the Dot/Icm type IVB translocation system.  The existence of such a large number of translocated effectors in L. pneumophila is an enigma that transcends the specific role of individual effectors. How was L. pneumophila able to acquire and maintain such a large arsenal of effectors? We answer these and other questions using comparative genomics and experimental evolution.