BICE · Behavioural Individuality in C. elegans
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2020-09-01 → 2023-05-14
- EU contribution
- €172,932
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Behavioural Individuality in C. elegans
Epigenetic marks such as histone methylation help to define how the DNA code is read. Alterations in this process can result in altered gene expression, a loss of cellular identity and cancer. To preserve expression patterns, epigenetic information must be correctly maintained. Thus, during the copying of the DNA strands that occurs before cell division, epigenetic marks must be transmitted to the new DNA strands. There are indications from cellular models that the machinery which duplicates DNA also participates in the transmission of epigenetic information. However, the replisome, the ensemble of proteins that participate in DNA replication, has not been characterised in a higher organism such as the roundworm C. elegans. In this project, we probed whether mutations in C. elegans replication components alter the transmission of epigenetic information. First, we used a fluorescent reporter assay to characterise interactions between replisome components in collaboration with another lab. Secondly, we tested the replisome mutants for fertility defects over generations, a phenotype that is associated with alterations in epigenetic transmission. Both approaches yielded novel insights into the function of the replisome, such as new genetic interactions that have not been reported to date. In addition, we found that combined loss of two non-essential factors increases gene expression, in regions that are normally repressed. We have indications that this increased expression in the double mutant is due to a loss of repressive histone marks. Furthermore, the double mutant exhibits a loss of fertility over generation which is reversible, and which can be repressed by downregulation of a histone demethylase. Our work describes for the first time the interplay of these two DNA replication factors and its effects on the transmission of epigenetic information.
Data: CORDIS, © European Union
Project objective
Animal behaviour is shaped by genetic traits, memories of past experiences and current internal states. Even in isogenic animal populations in a controlled environment, individual behaviour can be found. I obtained evidence that unexpectedly, the behaviour of adult C. elegans nematodes is influenced by the age of their mother. Progeny from young mothers explore less and dwell more in the same spot. I will exploit the model to characterise how the physiology of one generation determines the behaviour of the next generation. Second, I will determine additional environmental factors that imprint on C. elegans during development and thus modulate behaviour later in life. To examine the mechanism of maternal-age induced and environmentally induced behavioural variation, I will combine innovative genetic and pharmacological tools with state-of-the animal tracking and quantitative behavioural data analysis. I aim to determine the molecules and cells that sense and transmit the signals during development, and characterise the changes in neuronal wiring affecting behaviour in adult animals. Funding for this project will allow me to describe how 1) transgenerational effects such as maternal age and 2) environmental stimuli modulate behaviour later in life, in an amenable model organism such as C. elegans. Both parts of the project will partially overlap in time to complete the action within a 2-year time frame. As components of the nervous system are largely conserved between the nematodes and mammals, findings are likely to be extrapolated to higher animals.
Original text from CORDIS.
Participants
- FUNDACIO CENTRE DE REGULACIO GENOMICA · BarcelonaCoordinatorSpain
Links
Data: CORDIS, © European Union