Evolutionary genetics of Leishmania species with a focus on South America

Evolutionary genetics of Leishmania species with a focus on South America

Leishmania protozoans cause significant harm to several regions of the world with large populations, primarily affecting the poor in East Africa, the Middle East, the Indian subcontinent, and South America. Brazil and other regions of South America are affected by both visceral leishmaniasis (VL, caused by Leishmania infantum) and cutaneous leishmaniasis in a variety of forms (CL, caused by Leishmania mexicana, Leishmania braziliensis and multiple other species in the Viannia species complex). Neither case burdens nor treatment outcomes for VL or CL have improved very much in South America over the last decade.

Research in leishmaniasis is neglected, relative to the harm caused. For example, research and development of drugs, vaccines and sand fly vector control is poorly developed. The fundamental knowledge underpinning the applied approaches are also lacking, including an understanding of the evolutionary genetics of Leishmania species. This PhD will address this lack of fundamental knowledge, though analysis of comparative and population analysis of Leishmania species, focusing on species that are endemic in South America, via several related analyses.

Analysis will begin with comparative genomics, by completing high-quality genomes for all Leishmania species that have no, or low-quality genome assemblies, including outgroup/non-pathogenic species where appropriate, using Oxford Nanopore technology (ONT) reads. ONT and Illumina data for eight species are available now. Funds and contacts are available to obtain DNA and sequence up to 20 more species. Comparative genomics analyses of all of 30 Leishmania species will lead to a better understanding of molecular evolution in these parasites.

The second analyses will focus on population-genetic analysis of the VL-causing species L. infantum in Brazil, using an existing data set of ~400 strains distributed throughout Brazil and southern Europe. Our unpublished analysis shows that L. infantum arrived in Brazil with the colonisation by the Portuguese (~1600 CE). The student with utilise this data to produce population genetic models of the genetic diversity, population structure, dispersal, and breeding dynamics of this species in Brazil. There is potential within this PhD, to obtain and sequence further samples from several collaborators, and to contribute to ongoing analysis of the effects of L. infantum mutations on disease severity in dog and human hosts and/or to drug resistance.

The third analyses will focus on the Leishmania Viannia clade of approximately seven species, which cause CL in South America. This analysis will begin with existing data of at least 14 Viannia genomes from the seven species to describe the history of hybrid formation using an exhaustive genome-scale phylogenetic approach with haplotype-resolved ONT assemblies. Again, within this PhD there is there is potential for the student to take part in analysis of existing data (including 78 Leishmania guyanensis), and/or to obtain and sequence further samples from several collaborators. Some field work with collaborators would be possible.

This PhD will produce a highly-trained expert in population and comparative genomics, with considerable expertise in the genomic epidemiology of Leishmania species of South America.