The Signaling Dynamics of Host and Pathogen Interactions
Cell signaling research is challenged with the question of how specificity is achieved when different pathways share the same fundamental components. From a microbiology point of view, we are interested in understanding how bacteria can overcome the spatial and temporal dynamics of host signaling to mount an appropriate pathogenic response.
Our goal is to track the signaling dynamics of individual effectors and toxins in living cells, using a combination of fluorescent genetic reporters, microinjection of labeled bacterial proteins, and live cell imaging techniques.
From these studies, we learn about the kinetics of signaling between a pathogen and its host, findings that reveal fundamental causes of human infectious disease.
Enzymatic Properties Employed by Bacterial Effector Proteins
The bacterial Type III Secretion System (TTSS) is a concerted molecular machine that injects ‘effector’ proteins directly into the host cells. These effector proteins are evolutionarily tuned to hijack cellular signaling pathways that limit anti-microbial challenges and provide safe havens for bacteria in the host intracellular environment.
In recent years, molecular genetic approaches have led to the identification of numerous type III effector gene families, inspiring the search for their enzymatic activities and host substrates. We are continuously working on these problems by employing techniques such as yeast genetics, proteomics, and bioinformatics.
Our ultimate goal is to compare the mechanisms of type III effectors across species, thus providing invaluable information about how new bacterial pathogens emerge and how existing bacteria can be targeted by next generation antibiotic inhibitors.
Structure and Function of Bacterial Effector Proteins
Our laboratory collaborates extensively with the Structural Biology Laboratory (SBL) to solve the X-ray crystal structures of effectors in complex with host enzymes. The SBL provides facilities, reagents, and technical expertise to assist our efforts in the crystallization, optimization, and structural determination of co-complex structures of pathogenic molecules.
UT Southwestern houses a state of the art facility partially supported by Howard Hughes Medical Institute and run by world renowned X-ray crystallographers and structural biologists.
The structural determination of host-pathogen interactions are critical to our research as it uncovers fundamentally new principles in signal transduction.