Molecular regulation of social life

2 PhD project proposals in the IPP summer call 2019

PhD project 1: Gene Regulation and Division of labour

Social insects are models for the evolution of phenotypic plasticity as variation in gene expression chiefly controls caste development. Social insect workers specialise in specific tasks and this division of labour contributes to the ecological success of insect societies. Task specialisation is mostly neither genetically determined nor rigid, but changes with age and in response to colony needs. Typically, young workers takeover brood care, whereas older workers focus on risky tasks such as foraging. Indeed the expression of behavioural genes shifts with the tasks of workers (Feldmeyer et al. 2014; Kohlmeier et al. 2019) and (ii) histone acetylation can regulate task-specific gene expression (Simola et al. 2016).

Our hypothesis is that additional gene regulatory mechanisms, such as histone or DNA methylation are involved and may interact in regulating division of labour. We aim to understand how all of these regulatory processes respond to external cues, the expression of which genes they alter and how fast they can change gene expression. We analysed division of labour, the expression and functions of task-specific genes, and the importance of histone acetylation for their expression in the ant Temnothorax longispinosus. Theory posits that task switching requires shifts in responsiveness to task related cues and indeed, we identified a gene, vitellogenin-like A that regulates task allocation and social cue responsiveness (Kohlmeier et al. 2018): Once knocked down via RNAi, young workers reduce brood- but increase nestmate care, a behaviour usually exhibited by older workers. This behavioural change was accompanied by a vg-like A dependent shift in worker responsiveness from brood to adult worker cues. An experimental set-up allowed us to disentangle task from age and the following transcriptome analysis resulted in four times more genes linked to task than to age (Kohlmeier et al. 2019). Finally, the administration of the histone acetyltransferase (HAT) inhibitor C646 impeded the switch of foragers back to brood care, but promoted the reversed change from brood care to foraging. HAT inhibition did not affect workers continuing to execute the same tasks, pointing to the role of histone acetyltransferase in altering gene expression. HAT activity keeps young workers in a “brood caring mode”, possibly to prevent them from leaving the nest prematurely.

We will use ChipSeq analyses to identify genes associated with de-acetylated histones due to inhibition of C646 and we are analysing the associated changes in gene expression. In this project we will a) experimentally influence gene regulation using various epigenetic inhibitors, followed up by a behavioural readout and Chip-, RNA and ATAC Seq-analyses, to link the behavioural phenotype to gene expression and regulatory mechanisms e.g. splicing, b) study RNA and DNA methylation in the brain by reduced representation bisulfite sequencing, c) investigate which brain neuropils are responsible for behavioural changes (e.g. mushroom body, antennal lobes). We will collaborate with Peter Baumann and Susanne Gerber on Chip Seq and ATAC seq analyses. This project will deepen our understanding of the molecular regulation of division of labour in social insects.

Publications relevant to this project

Feldmeyer B, Elsner D and Foitzik S. (2014). Gene expression patterns associated with caste and reproductive status in ants: Worker-specific genes are more derived than queen-specific ones. Mol Ecol, 23: 151−161.

Kohlmeier P, Alleman A, Libbrecht R, Foitzik S* and Feldmeyer B.* (2019). Gene expression is more strongly associated with behavioural specialisation than with age or fertility in ant workers. Mol Ecol, 28: 658−670. (*indicates joint contribution)

Kohlmeier P, Feldmeyer B* and Foitzik S.* (2018). Vitellogenin-like A - associated shifts in social cue responsiveness regulate behavioral task specialization in an ant. Plos Biol, 16: e2005747. (*indicates joint contribution)

Simola DF, Graham RJ, Brady CM, Enzmann BL, Desplan C, Ray A, Zwiebel LJ, Bonasio R, Reinberg D, Liebig J and Berger SL. (2016). Epigenetic (re)programming of caste-specific behavior in the ant Camponotus floridanus. Science, 351: aac6633

PhD project 2: Parasite interference with gene regulation of a social host

The Extended phenotype concept (Dawkins, 1982) states that genes do not only affect the phenotype of their carrier, but also alter the latter’s biotic and abiotic environment. Especially parasites with complex life cycles manipulate the behaviour of their intermediate hosts to increase transmission to the definite host, ranging from alterations in pre-existing traits to the display of novel behaviours. Alterations in host gene expression are often associated with parasite-induced phenotypic changes.

We hypothesise that parasites manipulate host phenotypes to increase transmission by interfering with host gene regulation and are interested in which gene regulatory processes are affected. Infection of Temnothorax nylanderi ant larvae with the parasitic cestode Anomotaenia brevis strongly alters the adult phenotype. Parasitised workers exhibit altered behaviour, morphology, chemical profile and a lifespan extension (Scharf et al. 2012, Beros et al. 2015). We could show associated changes in gene expression e.g. the upregulation of longevity genes (Feldmeyer et al. 2016). This pointed to an improved ability of infected workers to deal with oxidative stress, which was supported by experiments with paraquat. The cestode, residing in its cysticercoid stage in the ants’ gaster is transcriptionally active and releases many proteins into the host. In collaboration with Falk Butter, we compared the proteome of the haemolymph of healthy workers and infected workers and contrasted it with that of the cestode. The vast majority of proteins that were only found in infected workers originated from the cestode. Bioinformatic analyses are on going to identify protein functions and to elucidate their role in gene expression interference.

To demonstrate that parasite-induced changes in host phenotype are actively promoted by the parasite, we will investigate how the cestode parasite 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) further investigating the cestode transcriptome to identify manipulative transcription modifiers (transcription factors, epigenetic regulators) and to test whether they are released into the host, b) Conduct an in-depth bioinformatic analysis of the proteome of the parasite and the haemolymph of infected / uninfected workers to identify released proteins and thereafter inject them in healthy workers to investigate their function, c) Study histone modifications and DNA methylation associated with parasite infection and link them to observed gene expression changes d) Contrasting the transcriptome during different developmental stages / body parts of infected / uninfected ants as infection occurs during the larval stage, d) Clear infection using antihelminthics and analyse changes in the phenotype, including gene expression and regulation and e) Phenotype host and cestode candidate genes using RNAi. We will collaborate with Falk Butter and Peter Baumann on proteomic and Chip Seq Analytical part of this project. This project will provide insights into the genetic and epigenetic underpinnings of behaviour and longevity in social insects shed light on across-species interference in gene regulation.

Publications relevant to this project

Beros S, Enders C, Menzel F and Foitzik S. (2019). Parasitism and queen presence interactively shape worker behaviour and fertility in an ant host. Anim Behav, 148:  63-70.

Beros S, Jongepier E, Hagemeier F and Foitzik S. (2015). A parasite’s long arm: A tapeworm parasite induces behavioural changes in uninfected group members of its social host. P Royal Soc B-Biol Sci, 282: 1819.

Dawkins R. (1982). The extended phenotype: The gene as the unit of selection. Oxford University Press, Oxford.

Feldmeyer B, Mazur J, Beros S, Lerp H, Binder H and Foitzik S. (2016). Gene expression patterns underlying parasite-induced alterations in host behaviour and life history. Mol Ecol, 25: 648–660.

Scharf I, Modlmeier AP, Beros S and Foitzik S. (2012). Ant societies buffer individual-level effects of parasite infections. Am Nat, 180: 671–683.

Contact Details

Prof. Susanne Foitzik