PhD: Pathways to parasitism in the kinetoplastids

United Kingdom
Oct 17, 2016
Jan 06, 2017
Organization Type
University and College
Full Time
The kinetoplastids are a group of single-celled eukaryotic parasites that cause devastating diseases of both animals and plants. In humans, kinetoplastids such as Trypanosoma and Leishmania cause diseases ranging from sleeping sickness and Chagas disease to leishmaniasis, and are a particular concern in the developing world. The virulence of kinetoplastid parasites is underpinned by a suite of cellular and genomic adaptations (Lukes et al. 2014). These include complex parasitic lifecycles that sometimes involve multiple hosts – such as the tsetse fly vector for sleeping sickness – the evolution of new effector proteins for interfering with host cells, and the re-organisation of internal cellular compartments such as the peroxisomes and mitochondria, which contain an unusual DNA-rich structure, the kinetoplast, after which this group of organisms was named. We do not yet know the order in which these structures evolved, nor which were the key evolutionary innovations that catalysed the evolution of parasitism within the clade.

Recent environmental DNA surveys have revealed that close relatives of kinetoplastid parasites are some of the most abundant organisms in the world’s oceans, and monitoring of UK fish and shellfish stocks has identified several novel fish and crustacean parasites that represent early-diverging members of the kinetoplastid clade. These parasites are distantly related to those causing disease in humans, but potentially share some of the same genomic adaptations. The aim of this project is to sequence the genomes of three of these new parasites, and compare them to existing kinetoplastid genomes, in order to address the following questions:

1. What is the environmental diversity of basal kinetoplastids, and how prevalent are they in UK aquaculture stocks?

2. How was the suite of adaptations observed in human-infecting kinetoplastids assembled during the evolution of the group, and which features are shared with the novel aquacultural parasites?

3. Can we identify parasitic genes shared across the kinetoplastids that might represent new drug targets?

This project is an industrial CASE collaboration between Dr. Tom Williams (Earth Sciences, University of Bristol), Prof. Wendy Gibson (Biological Sciences, Bristol) and Dr. David Bass (Cefas), and represents an exciting training opportunity to learn distinct but highly complementary sets of skills: bioinformatics (including genome assembly and analysis) from Dr. Williams, cell biology from Prof. Gibson and parasitological methods (sampling, histopathology, in situ hybridisation, transmission electron microscopy) at Cefas. You will be based at Bristol, but the project will also include a secondment at Cefas in Weymouth. These skills will equip you not only for a career in academic research, but also for a variety of other fields (government laboratory work, science applied to policy, diagnostics) and are valued in and transferable to data science, computing, and finance.