Speaker: Dr Ariel Blocker, University of Bristol, will present a seminar entitled: Function and structure of bacterial type III secretion systems

Date: 28^th June 2017
Time: 11:00am
Venue: QIB Lecture Theatre
Host: Lindsay Hall

Abstract:
Type III secretion systems (T3SSs) are essential devices in the virulence of many Gram-negative bacterial pathogens. They translocate bacterial virulence proteins into eukaryotic host cells to manipulate them during infection. T3SSs involved in virulence (vT3SSs) are related to bacterial flagella assembly apparatuses (fT3SS).

The importance of vT3SSs to human disease lead to their intensive study by many laboratories over the last two decades. In the last fifteen years, my laboratory provided insights into the vT3SS “base” that spans both bacterial membranes and the periplasm, the external and hollow “injection needle” embedded in the base and its distal tip complex which transforms itself into the translocation pore in the host cell membrane. We also helped work out the regulatory cascade within the bacterial cytoplasm that allows hierarchical substrate protein secretion. We thus illuminated how vT3SSs become activated for protein translocation by physical contact of the needle tip with host cells, a key step in infection initiation.

However, the mechanism of protein export through T3SSs remains unclear. During this talk, I will discuss our most recent studies of the cytoplasmic and inner membrane export apparatus (CEA and IMEA) of T3SSs using the fT3SS of Salmonella enterica sv. Typhimurium and the vT3SS of Shigella flexneri as models. These studies include electron cryotomography and subtomogram averaging for both systems, efforts to overexpress and purify the fT3SS IMEA and work to model and experimentally characterize the biochemical activities of its CEA, including its ATPase and the interaction of CEA components with IMEA ones.

Biography:
As a postdoctoral fellow at the Pasteur Institute in Paris, Dr Blocker visually identified and purified the type III secretion system (T3SS) of Shigella, the agent of bacillary dysentery in humans. She found they are composed of an external and hollow needle, a “base” region spanning both bacterial membranes and a cytoplasmic “bulb”. She performed some of the first studies of theT3SS translocon, the bacterial pore inserted by the T3SS into the host cell membrane to allow effector translocation.

As Senior Research Fellow at the Dunn School of Pathology Oxford, she demonstrated that the external “injection needle” subunit of the Shigella T3SS packs with the same helical symmetry as that of the bacterial flagellar hook and filament, to which it is evolutionarily but not sequence related. Her team found mutations within the needle component of the apparatus that lock the T3SS into secretion different “on” or “off” states, indicating that it is directly involved in transducing the host cell sensing signal. They discovered that these mutant needles also carry distal “tip complexes” of differing composition and functionality.

Upon arriving at the University of Bristol in 2008, her group performed a detailed structural and functional analysis of the tip complex, which showed it is the T3SS’s host-cell sensor. They also established that the host cell activation signal travels downwards from the tip complex via the needle to a conserved intrabacterial regulator. In the last two years, funded by a Wellcome Trust Investigator Award, they have focused their attention on the T3SS’s cytoplasmic and inner membrane export apparatus, trying to understand how it functions given its intriguing structure.

All staff from organisations on the Research Park are welcome to attend.