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Dissecting inclusion biogenesis – the specialised intracellular replicative compartment of Chlamydia trachomatis

Supervisor: Dr Richard Hayward
Based at the Division of Microbiology & Parasitology, Tennis Court Road

 Chlamydia trachomatis is the principal bacterial cause of sexually transmitted infections worldwide and ocular infections cause ‘trachoma’ a form of blindness in Developing nations, designated as a neglected tropical disease. Chlamydiae replicate within a specialised intracellular compartment termed an inclusion, which selectively engages host organelles but remains segregated from the endo-lysosomal system. Chlamydial virulence effector proteins are translocated into the host cell, but in most cases how they promote inclusion biogenesis remains poorly understood. This project will apply a multidisciplinary approach spanning biochemistry, cell biology, bioimaging and emerging genetic techniques in Chlamydia to further understand effector structure and function.

Confocal immunofluorescence micrograph showing a C.trachomatis inclusion within an infected cell surrounded by a ‘scaffold and nest’ of microtubules reorganised by the effector IPAM (see Dumoux et al, 2015).
C.trachomatis elementary body (EB) captured in contact with the host cell plasma membrane during invasion (see Nans et al, 2014).

Recent Publications

Pickering H, Teng A, Faal N, Joot H, Makalo P, Cassama E, Nabicassa M, Last A, Burr S, Rowland-Jones S, Thomson NR, Roberts C, Mabey DCW, Bailey R, Hayward RD, de la Maza L, Holland MJ (2017) Genome-wide profiling of humoral immunity and pathogen genes under selection identifies immune evasion tactics of Chlamydia trachomatis during ocular infection. Nature Scientific Reports 7:9634

Nans A, Kudryashev M, Saibil HR, Hayward RD (2015) Structure of a bacterial type III secretion system in contact with a host membrane in situ. Nature Communications 6:10114

Dumoux M, Menny A, Delacour D, Hayward RD (2015) A Chlamydia effector recruits CEP170 to reprogram host microtubule organization. Journal of Cell Science 128:3420-3434

Nans A, Saibil HR, Hayward RD (2014) Pathogen-host reorganization during Chlamydia invasion revealed by cryo-electron tomography.
Cellular Microbiology 16: 1457-1472

Dumoux M, Clare DK, Saibil HR, Hayward RD (2012) Chlamydiae assemble a pathogen synapseto hijack the host endoplasmic reticulum. Traffic 13:1612-1627