Research
Our research addresses the molecular basis of the interactions between disease-causing bacteria and their mammalian hosts. In particular, we study the intracellular biology of the obligate intracellular bacterium Chlamydia trachomatis. C.trachomatis is the leading bacterial agent of sexually transmitted disease worldwide and in developing nations causes blindness (trachoma), a neglected tropical disease.
Chlamydia forces its own entry into eukaryotic cells and forges a replicative niche within a specialised membrane-bound compartment (an ‘inclusion’), reprogrammed by the bacteria to mimic a host organelle. The inclusion remains segregated from the cellular endocytic pathway but is able to selectively engage with the secretory pathway.
Like some other Gram-negative bacteria including Salmonella and enteropathogenic E.coli, Chlamydia encodes a type III secretion system (T3SS), a sophisticated macromolecular assembly that spans the bacterial envelope and translocates virulence ‘effector’ proteins into mammalian cells. Remarkably, these effectors are often structurally distinct yet exquisitely mimic eukaryotic functions. Deciphering their subversive activities can provide critical insights into the mechanisms of infectious diseases and reveal potential new targets for therapeutics, diagnostics and vaccines. It also uncovers new assays and reagents to dissect the fundamental biology of cellular processes, including signal transduction, cytoskeletal dynamics, intracellular trafficking and cytokinesis.
Chlamydial effectors promote bacterial entry and replication, and the bacteria might translocate >50 effectors into cells. Some ‘inclusion proteins’ are characterised by a signature bi-lobed hydrophobic motif, whereas others remain anonymous within the genome in which a remarkable ~35% of open reading frames share no significant homology to either prokaryotic or eukaryotic proteins. Despite the importance of these events, comparatively little is know about the structure, function or targets of chlamydial effectors or the molecular mechanisms that underlie inclusion biogenesis. We are applying a combination of biochemical, cell biology and bio-imaging approaches to decipher these processes, in addition to applying recently emerging genetic techniques.
Publications
Andrew SC, Dumoux M, Hayward RD (2021)
Chlamydia uses K+ electrical signalling to orchestrate host sensing, inter-bacterial communication and differentiation
Microorganisms 9(1):173
Jarsch IK, Gadsby JR, Nuccitelli A, Mason J, Shimo H, Pilloux L, Marzook B, Mulvey CM, Dobramysl U, Bradshaw CR, Killey KS, Hayward RD, Vaughan TJ, Dobson CL, Gallop JL (2020)
A direct role for SNX9 in the biogenesis of filopodia.
Journal of Cell Biology 219(4):e201909178
Ford C, Nans A, Boucrot E, Hayward RD (2018)
Chlamydia exploits filopodial capture and a macropinocytosis-like pathway for host cell entry.
PLoS Pathogens 14:e1007051
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.
Scientific Reports 7: 9634
Cosse MM, Hayward RD, Subtil A (2016) [REVIEW]
One face of Chlamydia trachomatis: The Infectious Elementary Body.
Current Topics in Microbiology and Immunology
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
Dumoux M*, Nans A*, Saibil HR, Hayward RD (2015) [REVIEW]
Making connections: snapshots of chlamydial type III secretion systems in contact with host membranes.
Current Opinion in Microbiology 23: 1-7
Nans A, Saibil HR, Hayward RD (2014)
Pathogen-host reorganisation 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 synapse to hijack the host endoplasmic reticulum
Traffic 13:1612-1627
Brinkworth AJ, Malcolm DS, Pedrosa AT, Roguska K, Shahbazian S, Graham JE, Hayward RD, Carabeo RA (2011)
Chlamydia trachomatis Slc1 is a type III secretion chaperone that enhances the translocation of its invasion effector substrate TARP.
Molecular Microbiology 82: 131-144
Cain RJ*, Hayward RD*, Koronakis V (2008)
Deciphering interplay between Salmonella invasion effectors.
PLoS Pathogens 4: e1000037
Brawn LC, Hayward RD, Koronakis V (2007)
Salmonella SPI1 effector SipA persists after entry and cooperates with a SPI2 effector to regulate phagosome maturation and intracellular replication.
Cell Host & Microbe 1: 63-75
Hayward RD, Leong JM, Koronakis V, Campellone KG (2006) [REVIEW]
Exploiting pathogenic Escherichia coli to model transmembrane receptor signalling.
Nature Reviews Microbiology 4: 358-370
Phillips N, Hayward RD, Koronakis V (2004)
Phosphorylation of the enteropathogenic E.coli receptor by the Src-family kinase c-Fyn triggers actin pedestal formation.
Nature Cell Biology 6: 618-625
McGhie EJ, Hayward RD, Koronakis V (2004)
Control of actin turnover by a Salmonella invasion protein.
Molecular Cell 13: 497-510
McGhie EJ*, Hayward RD*, Koronakis V (2001)
Cooperation between actin-binding proteins of invasive Salmonella: SipA potentiates SipC nucleation and bundling of actin.
EMBO Journal 20: 2131-2139
Hayward RD, Koronakis V (1999)
Direct nucleation and bundling of actin by the SipC protein of invasive Salmonella.
EMBO Journal 18: 4926-4934
Recent collaborative work on other systems:
Wood TE, Howard SA, Forster Am Nolan LM, Manoli E, Bullen NP, Yau HCL, Hachani A, Hayward RD, Whitney JC, Vollmer W, Freemont PS, Filloux A (2019)
The Pseudomonas aeruginosa T6SS delivers a periplasmic toxin that disrupts bacterial cell morphology.
Cell Reports 29:187-201
Redzej A, Ukleja M, Connery S, Trokter M, Felisberto-Rodrigues C, Cryar A, Thalassinos K, Hayward RD, Orlova EV, Waksman G (2017)
Structure of a VirD4 coupling protein bound to a VirB type IV secretion machinery.
EMBO Journal 36:3080-3095
Prevost MS, Pinotsis N, Dumoux M, Hayward RD, Waksman G (2017)
The Legionella effector WipB is a translocated Ser/Thr phosphatase that targets the host lysosomal nutrient sensing machinery.
Scientific Reports 7:9450
Teaching and Supervisions
Part II Pathology (NST & BBS): Microbiology Option Organiser; lecturer in cellular microbiology; journal seminar and research presentation coordinator; supervisions; laboratory hosts NST project students; BBS dissertation supervisor
Part Ib Biology of Disease (NST, MST, VST): Microbiology practical lead; lecturer
Current Group Members
Dr Ludovic Pilloux
Miss Simone Adams
Opportunities - postdoctoral researchers, graduate students and undergraduate placements
We are constantly seeking to recruit enthusiastic and motivated scientists at all levels. Our work is multidisciplinary and currently involves a combination of molecular microbiology, bacterial genetics, protein biochemistry, cell biology and bioimaging (fluorescence, confocal and electron microscopy), although we welcome new skills that compliment these disciplines.
Postdoctoral researchers should make contact informally, explaining their interests and motivations, and attaching a CV. Funded positions will be advertised here, and fellowship applications from suitable candidates are also encouraged.
Prospective postgraduate students are welcome to make informal contact, but usually must apply to the institutional PhD Programmes, although other opportunities may be available.
We have also hosted Masters, international short-term students and undergraduate summer studentships.
