Developmental genetics, genomes and evolution of helminth parasites

A microscopic image of a tapeworm. Parts of the insides of the worm are showing up in blue.

Parasitic worms are principal agents of Neglected Tropical Diseases and a major economic burden on livestock and farming across all regions of the globe.

Efforts to control helminth parasitism in ourselves and the animals we rely on for food, work and companionship require contemporary approaches and tools for understanding the genetic basis of their growth and form. This is what we have been helping to develop.

Tapeworms are common parasitic flatworms well known for their propensity for proliferative growth. The adult tapeworm body enables the production of a continuous chain of segments, each with the ability to produce thousands of eggs and represents a novel, adaptive feature of the group that underpins their transmission in the wild.

Understanding the genetic pathways that orchestrate their growth is key to understanding the evolution of parasitism in the group and provides inroads to new targets for intervention.

Project aims

We aim to elucidate the gene regulatory systems that pattern tapeworm bodies throughout their complex life cycle, regulate sexual development and maintain their unique stem cell system.

The segments of a worm lit up in purple

Methods

We use a classical mouse/beetle-hosted model tapeworm system, Hymenolepis microstoma, in which we have developed tools for visualising gene expression alongside extensive genomic resources that underpin the ability to investigate their developmental genetics, including the first fully characterised genome of a flatworm. We have used this system to investigate the dynamic and regionalised expression of Wnt genes which are universal regulators of axial patterning in animals, as well as having roles in cell proliferation, differentiation and migration.

We aim to advance this work and laboratory platform by employing new technologies in sequencing that allow for the circumscription of the genes that define different cell types, including their unique somatic stem cells; through investigation of the implications of their unusual chromosome architecture; and through broader, comparative genomic studies that can provide an evolutionary perspective on the tapeworm’s unique form and function among the parasitic flatworms.

Who is involved?

Genomic studies are conducted in collaboration with Professor Matt Berriman from the University of Glasgow and the Sanger Institute. Developmental studies are in collaboration with Professor Uriel Koziol from the University de la Republica in Uruguay.

The meiosis gene boule expressed in the testes and ovaries of tapeworm segments

Jarero et al. 2024. Muscular remodelling and anteroposterior patterning during tapeworm segmentation. Developmental Dynamics   DOI:10.1002/dvdy.712

Olson et al. 2020. Complete representation of a tapeworm genome reveals chromosomes capped by centromeres, necessitating a dual role in segregation and protection. BMC Biology 18:165   DOI:10.1186/s12915-020-00899-w

Int. Helminth Genomes Consortium. 2019. Comparative genomics of the major parasitic flatworms. Nature Genetics 51:163-174   DOI:10.1038/s41588-018-0262-1

Olson et al. 2018. Genome-wide transcriptome profiling and spatial expression analyses identify signals and switches of development in tapeworms. BMC Evo Devo 9:1-29   DOI:10.1186/s13227-018-0110-5

Koziol et al. 2016. Comparative analysis of Wnt expression identifies a highly conserved developmental transition in flatworm. BMC Biology 14:1-17  DOI:10.1186/s12915-016-0233-x

Muehlenbachs et al. 2015. Malignant transformation of Hymenolepis nana in a human host. New England Journal of Medicine 373:1845-52   DOI:10.1056/NEJMoa1505892

Tsai et al. 2013. The genomes of four tapeworms reveals adaptations to parasitism. Nature 496:57-63   DOI: 10.1038/nature12031

Focus: Understanding the genetic basis of development in helminth parasites, especially tapeworms.

Dates: Ongoing

Funding: Biotechnology and Biological Sciences Research Council (BBSRC), Natural Environment Research Council (NERC) and the Wellcome Trust Sanger Institute.