Imperial College London
Alternate

DrMatthewChild

Faculty of Natural Sciences, Department of Life Sciences

Research Fellow (Sir Henry Dale Fellow)
 
 
 
//

Contact

 

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

 
 
//

Location

 

603Sir Alexander Fleming BuildingSouth Kensington Campus

//

Summary

 

Publications

Citation

BibTex format

@unpublished{Wincott:2020:10.1101/2020.08.06.239822,
author = {Wincott, CJ and Sritharan, G and Benns, HJ and Liakath, FB and Gilabert-Carbajo, C and Bunyan, M and Fairweather, AR and Alves, E and Andrew, I and Game, L and Frickel, EM and Tiengwe, C and Ewald, SE and Child, MA},
doi = {10.1101/2020.08.06.239822},
title = {Cellular barcoding of protozoan pathogens reveals the within-host population dynamics of <i>Toxoplasma gondii</i> host colonization},
url = {http://dx.doi.org/10.1101/2020.08.06.239822},
year = {2020}
}
Download

RIS format (EndNote, RefMan)

TY  - UNPB
AB  - <jats:title>Abstract</jats:title><jats:p>Molecular barcoding techniques have emerged as powerful tools to understand microbial pathogenesis. However, barcoding strategies have not been extended to protozoan parasites, which have unique genomic structures and virulence strategies compared to viral and bacterial pathogens. Here, we present a versatile CRISPR-based method to barcode protozoa, which we successfully apply to <jats:italic>Toxoplasma gondii</jats:italic> and <jats:italic>Trypanosoma brucei</jats:italic>. The murine brain is an important transmission niche for <jats:italic>T. gondii</jats:italic>, and brain persistence is a clinically untreatable feature of infection. The blood-brain barrier is expected to physically restrict parasite colonization of this niche, resulting in a selection bottleneck. Using libraries of barcoded <jats:italic>T. gondii</jats:italic> we evaluate shifts in the population structure from acute to chronic infection of mice. Contrary to expectation, most barcodes were present in the brain one-month post-intraperitoneal infection in both inbred CBA/J and outbred Swiss mice. Although parasite cyst number and barcode diversity declined over time, barcodes that represented a minor fraction of the inoculum could become a dominant population in the brain by three months post-infection. Together, these data establish the first, robust molecular barcoding approach for protozoa and evidence that the blood-brain barrier does not represent a major bottleneck to colonization by <jats:italic>T. gondii</jats:italic>.</jats:p>
AU  - Wincott,CJ
AU  - Sritharan,G
AU  - Benns,HJ
AU  - Liakath,FB
AU  - Gilabert-Carbajo,C
AU  - Bunyan,M
AU  - Fairweather,AR
AU  - Alves,E
AU  - Andrew,I
AU  - Game,L
AU  - Frickel,EM
AU  - Tiengwe,C
AU  - Ewald,SE
AU  - Child,MA
DO  - 10.1101/2020.08.06.239822
PY  - 2020///
TI  - Cellular barcoding of protozoan pathogens reveals the within-host population dynamics of <i>Toxoplasma gondii</i> host colonization
UR  - http://dx.doi.org/10.1101/2020.08.06.239822
ER  -
Download