Dr Daniel Humphreys
Room: C 08 Florey building
Manipulation of mammalian host cell biology by bacterial toxins and virulence effectors.
Manipulation of mammalian host cell biology by bacterial toxins and virulence effectors
To establish infections within mammalian hosts, bacterial pathogens have evolved sophisticated strategies to exploit host cell biology. They deploy toxins and virulence effector proteins into our cells that hijack cellular processes to promote pathogen survival, replication and dissemination, and interfere with the host immune response.
We are interested in the cell biology subverted by bacterial pathogens and how this ultimately contributes to diseases that can have devastating consequences to the health of humans and animals. Understanding host-pathogen interactions is especially important when considering the human health threat posed by many bacterial pathogens that continue to develop multidrug resistance.
Bacterial pathogens are known to inject virulence effectors that hijack the actin cytoskeleton. For example, enteropathogenic and enterohaemorrhagic Escherichia coli generate ‘actin pedestals’ to colonise the host cell surface whilst Salmonella and Shigella invade cells by generating ‘membrane ruffles’.
Once inside cells, Salmonella survives within a vacuole and ‘evades destruction within lysosomes’. Shigella on the other hand uses ‘actin-based propulsion to ‘’rocket’ through the cell and even propel itself into uninfected neighbouring cells for dissemination. Salmonella, E.coli and Shigella also secrete cytolethal distending toxins that cause DNA damage to induce ‘cell cycle arrest’ and interfere with immune cell signalling.
There are currently no positions available in the lab. However, we always welcome speculative applications.
To express interest, please feel free to email me your CV and research interests.
- Brooks ABE, Humphreys D, Singh V, Davidson AC, Arden SD, Buss F & Koronakis V (2017) MYO6 is targeted by Salmonella virulence effectors to trigger PI3-kinase signaling and pathogen invasion into host cells. Proceedings of the National Academy of Sciences. View this article in WRRO
- Humphreys D, Singh V & Koronakis V (2016) Inhibition of WAVE Regulatory Complex Activation by a Bacterial Virulence Effector Counteracts Pathogen Article Inhibition of WAVE Regulatory Complex Activation by a Bacterial Virulence Effector Counteracts Pathogen Phagocytosis. Cell Reports, 17, 697-707. View this article in WRRO
- Humphreys D, Davidson AC, Hume PJ, Makin LE & Koronakis V (2013) Arf6 coordinates actin assembly through the WAVE complex, a mechanism usurped by Salmonella to invade host cells.. Proceedings of the National Academy of Sciences of the United States of America, 110, 16880-16885.
- Humphreys D, Davidson A, Hume PJ & Koronakis V (2012) Salmonella Virulence Effector SopE and Host GEF ARNO Cooperate to Recruit and Activate WAVE to Trigger Bacterial Invasion. Cell Host and Microbe, 11, 129-139.
- Humphreys D, Liu T, Davidson AC, Hume PJ & Koronakis V (2012) Drosophila Arf1 homologue Arf79F is essential for lamellipodia formation. Journal of Cell Science, 1, 5630-5635.
- Humphreys D, Hume PJ & Koronakis V (2009) Article The Salmonella Effector SptP Dephosphorylates Host AAA + ATPase VCP to Promote Development of its Intracellular Replicative Niche. Cell Host and Microbe, 225-233.