Susanne Franssen - Evolutionary and Pathogen Genomics
We are interested in the genetic basis of evolutionary change from short time scales within populations up to divergence on the between species level. We study these using a combination of genomics, population genetics, phylogenetics and simulation approaches to understand evolution of natural as well as experimentally evolved populations.
Parasite Population genomics
Our focal parasite genus is the protist parasite Leishmania. It is a eukaryotic unicellular parasite that is transmitted by sand flies and infects humans and other mammalian hosts causing the neglected tropical disease leishmaniasis in humans. Disease phenotypes can be cutaneous causing localised, diffuse or mucosal lesions or visceral disease with the latter being fatal without treatment. Leishmania hotspot regions include the Indian Subcontinent, Africa and South America, however, Leishmania infantum is also endemic in Southern Europe, where it is now better known for causing leishmaniosis in dogs.
A few characteristics of Leishmania make its population genetics very unusual. This includes its complex life cycle alternating between the sand fly vector and the human host. While in the vector it is present as extracellular promastigotes, in the mammalian host it becomes intracellular infecting macrophages. In the intracellular stage it is so far only known to reproduce clonally, but in the sand fly vector hybridisation was also shown to occur. An additional characteristic of Leishmania is its mosaic aneuploidy. Here, the different chromosomes can not only been present in different chromosome copy numbers (aneuploidy) between strains, but copy numbers even quickly vary between individual cells in a clonal population grown from a single cell.
To address questions in Leishmania population genomics, we work with samples from natural populations including data from clinical and veterinary isolates and collaborate with scientists from different backgrounds including immunology, epidemiolgy and clinical expertise.
Experimental evolution is a tool to study adaptation in real time, while confounding factors such as geography or multiple environmental differences can be controlled for. Experiments can either actively select for specific phenotypes of interest or have the populations evolve to defined laboratory environments. In so called Evolve & resequence studies, populations are then whole-genome sequenced at particular time intervals to identify genomic changes that are repeatedly associated with either the selected phenotype or Darwinian fitness in the defined lab environment.
In Leishmania, we are particularly interested in using experimental evolution to understand mosaic aneuploidy in Leishmania and its role during adaptation as opposed to single nucleotide changes. Additionally, we are also studying selection of signatures in more classical systems of sexually reproducing diploid organisms and computational and analytical methods to identify and characterise them.
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Background information on leishmaniasis: