Jo Stevens

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Current Research Interests

Studies intracellular bacterial pathogens, with specific interest in the bacterial genes required for intracellular survival and evasion of innate immune responses.

Research Interests

The melioidosis pathogen Burkholderia pseudomallei is a facultative intracellular pathogen of humans and animals that enters non-phagocytic cells, escapes from endosomes and propels itself within and between cells by continuous polymerisation of actin at one bacterial pole (known as actin based motility). Actin-based motility is also a feature of infection by the closely related glanders pathogen B. mallei and the avirulent saprophyte B. thailandensis.

With previous BBSRC support, I have unravelled how B. pseudomallei stimulates actin assembly to propel itself within and between eukaryotic cells. I characterised a factor required for intracellular actin-based motility (BimA), surveyed its diversity in natural populations and identified functional orthologues in other Burkholderia species . BimA is required for intracellular survival, intercellular spread and virulence and acts in a manner distinct from most other pathogen-associated factors required for actin-based motility. Moreover, I recently found that BimA from closely-related Burkholderia species use distinct strategies to nucleate actin. B. thailandensis BimA recruits and activates a cellular complex that assembles actin (Arp2/3) via a unique central acidic domain, whereas B. pseudomallei BimA exhibits an intrinsic Arp2/3-independent ability to nucleate actin in a manner akin to eukaryotic formin- and spire-family proteins.

My ongoing research is aimed at further understanding the mechanisms by which BimA proteins from related Burkholderia species function as actin nucleators. Towards this aim I am trying to understand how posttranslational modifications of the proteins affect function as well as define any differences in the host cell proteins they may interact with. I am also investigating the role of BimA and actin-based motility in the evasion of intracellular recognition and killing mechanisms in host cells.

 

Qualifications

BSc. (Hons) Microbiology, Class 2(I), University of Reading, 1996.

PhD Molecular Virology, Thesis Title: Assembly of Influenza Viruses, University of Reading, 2000.

Biography

Since obtaining my PhD on the subject of ‘Influenza Virus Assembly Mechanisms’ in 2000, I have worked on cell signalling mechanisms of human platelets and host: pathogen interactions of bacterial intracellular pathogens. As Group Leader at The Roslin Institute, my group focuses on the study of bacterial pathogens of both clinical and veterinary importance. We are interested in identifying novel virulence factors and understand how these microbes evade cell-autonomous immunity mechanisms. Common approaches include bacterial genetic manipulation, quantitative proteomics, protein-protein interaction techniques (i.e. Y2H), siRNA knockdown and CRISPR-Cas9 gene editing. Our goal is to carry out basic science that will ultimately inform the design of diagnostic assays, novel vaccines and treatments.

In addition to my scientific research interests, I am also Postgraduate Convenor for the Division of Infection and Immunity, manage the Containment Level 3 laboratory at Roslin and perform the role of GM Biological Safety Officer for the Easter Bush Campus.

Education/Academic qualification

Assembly of Influenza Viruses, Doctor of Philosophy (PhD), University of Reading

1999

Award Date: 1 Jan 2000

Microbiology, Bachelor of Science, University of Reading

1996

Award Date: 1 Jan 1996

External positions

BBSRC-funded postdoctoral scientist, 'Molecular analysis of actin-based motility of Burkholderia spp', Division of Microbiology, Institute for Animal Health, Compton

Oct 2007Oct 2010

BBSRC-funded postdoctoral scientist, 'Exploitation of host cells by Burkholderia pseudomallei', Division of Microbiology, Institute for Animal Health, Compton

Feb 2004Sep 2007

BHF-funded post-doctoral scientist, 'Generation and use of knockout mice to investigate the role of integrin-linked kinase in platelets', University of Reading

Oct 2002Jan 2004

BBSRC-funded post-doctoral scientist, 'The role of integrin-linked kinase in platelet cell signalling', University of Reading

Oct 1999Sep 2002

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