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Investigating Parasite interference in regulation of host gene expression

Supervisor: Susanne Foitzik

Co-Supervisor: Peter Baumann, Joan Barau

 

Scientific Background:
Many parasites, especially those with complex life cycles, manipulate life history traits and behaviour of their hosts to increase transmission. Alterations in host gene expression are often linked to these parasite-induced phenotypic changes - termed the parasites’ extended phenotype by Dawkins. We hypothesise that parasites manipulate host phenotypes by interfering with host gene regulation and test whether and how they do this on a molecular level. In particular, we want to elucidate which gene regulatory processes they interfere with. Infection of Temnothorax nylanderi ant larvae with the parasitic cestode Anomotaenia brevis strongly transforms the adult phenotype of these ants. Infected workers exhibit altered behaviour, morphology, chemical profile and an extreme lifespan extension (Beros et al. 2015, Beros et al. 2021). In a three-year study, the survival rates of infected workers matched those of queens, which can reach 20 years in this species (Beros et al. 2021). We could show associated changes in gene expression e.g. the upregulation of immunity and longevity genes (Feldmeyer et al. 2016, Stoldt et al. 2021), such as the silver gene carboxypeptidase Blike, linked to postponed senescence in D. melanogaster. Recent results show that infection intensity strongly affects fat body transcriptomes, with genes with telomerase maintenance, apoptosis and transposon activity functionalities being differentially expressed between highly infected ants (over 18 cestodes) and lowly infected (1 cestode) or uninfected ants. The cestode, residing in its cysticercoid stage in the haemolymph of the ants’ abdomen is transcriptionally active (Stoldt et al. 2021). In collaboration with Falk Butter, we compared the proteomes of the haemolymph of healthy workers + queens and infected workers and contrasted them with that of the cestode (N = 22 pooled samples from 8 colonies). The majority of proteins only found in infected workers originated from the cestode. Bioinformatic analyses reveal that the cestode is releasing proteins affecting lifespan (antioxidants e.g. superoxide dismutases or thioredoxin) and gene regulatory processes including histone acetylation and the piwi-pathway. The next steps are to investigate how epigenetic processes are altered in infected ants.

 

PhD project: Investigating Parasite interference in regulation of host gene expression
To demonstrate to which extent and how parasite-induced changes in host phenotype are actively promoted by the parasite, we will investigate how the cestode interferes with the hosts’ gene regulation, which gene-regulatory mechanisms are utilised and whether these alterations are permanent or have to be actively maintained. We will do this by
a) studying histone modifications (using ChIP-seq and CUT&RUN), DNA methylation (Bisulfite-Seq), miRNA and lncRNAs associated with parasite infection and link them to observed transcriptomic changes,
b) altering the infection status by clearing the infection (using antihelminthics) or infecting ants experimentally and analysing changes in the phenotype, including gene expression and regulation and
c) Phenotyping host and cestode candidate genes using RNAi.

Peter Baumann and Joan Barau will contribute their expertise ChIP-Seq and CUT&RUN analyses. This project is linked to others within GenEvo providing insights into the genetic and epigenetic underpinnings of behaviour and longevity and across-species interference in gene regulation.

 

Publications relevant to this project
Beros S, Jongepier E, Hagemeier F and Foitzik S. (2015). The parasite’s long arm: A tapeworm parasite induces behavioural changes in uninfected group members of its social host. Proc R Soc B Biol Sci, 282: 20151473.
Beros, S., Lenhart, A., Scharf, I., Negroni, M.N., Menzel, F., Foitzik, S. (2021) Extreme lifespan extension in tapeworminfected ant workers. Royal Society Open Science, 8(5):202118.
Feldmeyer B, Mazur J, Beros S, Lerp H, Binder H and Foitzik S. (2016). Gene expression patterns underlying parasiteinduced alterations in host behaviour and life history. Mol Ecol, 25: 648–660.
Stoldt, M., Klein, L., Beros S., Butter, F., Jongepier, E., Feldmeyer B., Foitzik, S. (2021) Parasite presence induces gene expression changes in an ant host and their function in immunity and longevity. Genes, 12: 95.