Download Using whole genome sequence data to develop

SGUL/LSHTM MRC London Intercollegiate Doctoral Training Partnership – 2017/18 Potential PhD Projects
Title of PhD project
Using whole genome sequence data to develop
molecular barcodes to profile Plasmodium malaria
parasites
Supervisor
Dr Susana Campino
LSHTM
Co-Supervisor
Prof Taane Clark
LSHTM
Brief description of project
Plasmodium falciparum malaria is a major threat to human
health causing over 300 million clinical cases per year and an
estimated ~1 million deaths. Malaria eliminating countries are
increasingly concerned with identifying pockets of
transmission and outbreaks arising from imported cases, and
there is a need to establish molecular barcodes for
implementation in the field. The genetic diversity and nonrecombining properties of mitochondrial and apicoplast
sequence can be powerfully exploited for geographic genetic
profiling of P. falciparum malaria at an inter-continent level
[1]. However, this approach would be limited for assessing
transmission intensity [2] and drug resistance [3], intraregional geographical differentiation, and ignores malaria
caused by other plasmodia (P. knowlesi, P. ovale, P.
malariae, P. vivax). To overcome these limitations, this
project proposes to develop barcodes using nuclear,
apicoplast and mitochondria genomes for all human malaria
species. In particular, it will involve: (1) the construction of a
library of genomic sequence variants across Plasmodium
species using bioinformatic approaches [4], and an
assessment of genetic diversity; (2) the development of
molecular barcodes to profile and differentiate species and
geographical regions by identifying informative markers using
statistical, population genetic and machine learning methods
[5]; (3) the testing of the barcodes using prospectively
collected datasets, particularly from endemic settings with
complex mixed infections and regions with drug resistance.
A growing collection of P. falciparum, P. knowlesi, and P.
vivax public raw sequences (n>2,200) with meta data are
available immediately for analysis [4,6,7]. The identification of
markers could inform future rapid diagnostics, and promote
the application of field-based portable sequencing devices
(e.g. MinIon) linked to an informative database and profiling
tool using mobile phone technology; thereby assisting malaria
control programmes and clinical management.
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SGUL/LSHTM MRC London Intercollegiate Doctoral Training Partnership – 2017/18 Potential PhD Projects
References
[1] www.who.int
[2] Preston MD, Campino S,…, Clark TG (2014a). Nature
Commun. 2014; 5:4052.
[3] Assefa S, …., Clark TG (2014). Bioinformatics 30(9):12924.
[4] Borrmann S, …, Campino S,..., Clark TG (2013). Scientific
Reports 25;3:3318.
[5] Preston MD, …, Clark TG (2014b). J Infect Dis 209:180815.
[6] Samad H, …, Clark TG (2015). PLoS Genet
11(4):e1005131
[7] Ravenhall M, .., Campino S & Clark TG (2016). Malaria J
(in press).
Particular prior educational
requirements for a student
undertaking this project
Standard School research degree entry requirements
Skills we expect a student
to develop/acquire whilst
pursuing this project
Bioinformatics, pathogen genomics, malaria genetics,
statistical and population genetics, malaria, plasmodium and
molecular biology, epidemiology
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