Elucidating the mechanisms of outer membrane biogenesis in Gram-negative bacteria

"Antibiotic resistance a driving force in a persistent and rising global heath crisis. Of particular note are the Gram-negative bacterial species, which have an extra in-built level of protection against antibiotics in the form of their outer membrane. This outer membrane acts as a barrier against toxins including antibiotics and is asymmetric in nature with an outer leaflet composed of lipopolysaccharides and an inner leaflet made up of phospholipids. This asymmetry is tightly regulated, however the mechanisms which facilitate this have yet to be fully determined. Characterisation of these mechanisms is of critical importance, as disrupting these systems would be a major step forward in the fight against the increasing threat of antibiotic resistance.
In recent years, Mammalian cell entry (MCE) domain containing proteins have come to light as possible phospholipid transport systems within several Gram-negative bacterial species. This project therefore aims to study this diverse family of MCE domain containing proteins using techniques such as Förster resonance energy transfer-based functional assays, cryo-electron microscopy and neutron reflectometry to further determine their structure, interaction, and function within the context of phospholipid transport."