Doyle Group

Helminth Genomics 

The Helminth Genomics team, led by Dr. Stephen Doyle, uses multidisciplinary approaches to understand genetic and phenotypic variation in parasitic worms that infect humans and animals. We generate and analyse population-wide to single-cell resolution genomic datasets to understand the genetic basis for parasitic worms' evolutionary success and future potential and to identify evolutionary constraints that may be exploited to control them.

Genomics increasingly plays a critical role in understanding parasite worm biology. At the foundation of many wet and dry lab studies is the reference genome, which can provide great insights into the form and function of parasites and the evolutionary processes that make them successful. We have led and contributed to generating high-quality reference genomes for several parasitic worm species, supporting ongoing curation of genome annotations and resources that are shared openly for our work and the parasitology community. These resources are primarily shared via WormBase ParaSite, an invaluable resource for helminth biology that we contribute to and make use of constantly. We have led the generation of rich datasets to understand parasite biology, including developmental transcriptional timecourses and are currently working on single-nuclei RNAseq and spatial transcriptomic atlases to both better understand the developmental biology of these parasites and reveal greater knowledge of the expression characteristics of many genes of unknown function.

A strong theme in the group is focused on understanding parasite responses to drug treatment. We use natural host-parasite systems such as Haemonchus contortus in sheep and field isolates of parasites such as Teladorsagia circumcincta and Dirofilaria immitis collected from around the world to map genetic variation associated with drug resistance to the vital drug classes used to control parasitic worms. In humans, we have contributed to the understanding of the genetics of praziquantel resistance in Schistosoma mansoni and are currently focused on understanding treatment response variation in large cohorts of soil-transmitted parasites collected as part of clinical trials to evaluate new approaches for control.

The ability to accurately and sensitively diagnose parasite infections is at the forefront of efforts to control parasites as a public health problem and their elimination. We have surveyed soil-transmitted helminth diversity to understand the impact of genetic variation on the success of molecular diagnostics and are currently developing scaleable and portable amplicon sequencing approaches to detect mixed parasite infections. We aim to use these tools to measure the impact of treatment approaches and interactions with other variables, such as environmental and health outcomes, on parasite community diversity.

Collectively, the Helminth Genomics team aims to build foundational knowledge of parasites that infect humans and animals and to use this knowledge to improve the control of parasites as a human and animal health burden worldwide.