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Mechanisms of host cell subversion by the human pathogen 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 disease worldwide and ocular infections cause a form of blindness (trachoma) in Developing nations, designated as a neglected tropical disease. Chlamydiae replicate within eukaryotic host cells by building a specialised intracellular compartment termed an inclusion, which selectively engages host organelles but remains segregated from the endo-lysosomal system. Chlamydial ‘effector’ proteins, which are delivered into the host cell, direct the biogenesis of this remarkable pseudo-organelle but in most cases their functions remain poorly characterised. This project will apply a multidisciplinary approach spanning biochemistry, cell biology, bioimaging and emerging genetic techniques in Chlamydia to understand effector structure and function.

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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).
 
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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