Imperial College London
Alternate

DrMatthewChild

Faculty of Natural Sciences, Department of Life Sciences

Research Fellow (Sir Henry Dale Fellow)
 
 
 
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Contact

 

+44 (0)20 7594 5402m.child Website

 
 
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Location

 

603Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Child:2013:10.1038/nchembio.1315,
author = {Child, MA and Hall, CI and Beck, JR and Ofori, LO and Albrow, VE and Garland, M and Bowyer, PW and Bradley, PJ and Powers, JC and Boothroyd, JC and Weerapana, E and Bogyo, M},
doi = {10.1038/nchembio.1315},
journal = {Nat Chem Biol},
pages = {651--656},
title = {Small-molecule inhibition of a depalmitoylase enhances Toxoplasma host-cell invasion.},
url = {http://dx.doi.org/10.1038/nchembio.1315},
volume = {9},
year = {2013}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Although there have been numerous advances in our understanding of how apicomplexan parasites such as Toxoplasma gondii enter host cells, many of the signaling pathways and enzymes involved in the organization of invasion mediators remain poorly defined. We recently performed a forward chemical-genetic screen in T. gondii and identified compounds that markedly enhanced infectivity. Although molecular dissection of invasion has benefited from the use of small-molecule inhibitors, the mechanisms underlying induction of invasion by small-molecule enhancers have never been described. Here we identify the Toxoplasma ortholog of human APT1, palmitoyl protein thioesterase-1 (TgPPT1), as the target of one class of small-molecule enhancers. Inhibition of this uncharacterized thioesterase triggered secretion of invasion-associated organelles, increased motility and enhanced the invasive capacity of tachyzoites. We demonstrate that TgPPT1 is a bona fide depalmitoylase, thereby establishing an important role for dynamic and reversible palmitoylation in host-cell invasion by T. gondii.
AU  - Child,MA
AU  - Hall,CI
AU  - Beck,JR
AU  - Ofori,LO
AU  - Albrow,VE
AU  - Garland,M
AU  - Bowyer,PW
AU  - Bradley,PJ
AU  - Powers,JC
AU  - Boothroyd,JC
AU  - Weerapana,E
AU  - Bogyo,M
DO  - 10.1038/nchembio.1315
EP  - 656
PY  - 2013///
SP  - 651
TI  - Small-molecule inhibition of a depalmitoylase enhances Toxoplasma host-cell invasion.
T2  - Nat Chem Biol
UR  - http://dx.doi.org/10.1038/nchembio.1315
UR  - https://www.ncbi.nlm.nih.gov/pubmed/23934245
VL  - 9
ER  -
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