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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. 1 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 2