While neuronal plasticity is a critical element in cognitive phenomena, the complexity of metazoan models makes it difficult to study these phenomena at the cellular and molecular scales. Also, the exploration of less complex biological models should make it possible not only to lay down molecular bases, but also the primitive mechanisms of cognition. Although a few studies suggest that changes in histones influence neuronal plasticity, the epigenetic mechanisms in cognition are still unclear. However, to improve the diagnosis of certain cognitive disorders, clinical trials are currently underway with molecules that inhibit histone acetylases (HDAC). In view of these data, it is reasonable to think that a rational exploration of histone modifications in a cognitive context should open up new avenues.
Assumptions and questions
The slime mold Physarum polycephalum, also known as Blob, is a model of definite interest in cognitive studies. For our study, we will pay particular attention to the habituation which corresponds to a simple form of learning and which has been described in the literature. Besides the habituation, a similar approach has also shown the Blob’s ability to teach naïve congeners. However, epigenetic analyzes of these phenomena are lacking. Also, the project consists of filling this gap by taking advantage of our long-standing expertise, both on the original biological model, Physarum, and on that of epigenetic studies.
The main steps of the thesis and scientific procedure
The candidate will be trained in Physarum cultures under axenic conditions. First, habituation experiments will be carried out through the use of repellent molecules (sodium chloride, quinine and caffeine). Once habituation is in place, analyzes of the epigenome will be done by Western blot to examine changes in histone post-translational modifications and by genomic approaches (CUT & RUN). In a second step, learning experiments will be carried out using naive cells and cells which have established the habituation. After observing the learning by the naive cells, analyzes of the epigenome will be done as before.
Methodological and technical approaches considered
The envisaged approaches are basic techniques of culture of Physarum in axenic conditions. epigenome studies will be performed by biochemical chromatin analysis approaches such as western blotting and CUT & RUN.
Recent relevant publications of the team
- Physarum polycephalum for studying the function of histone modifications in vivo. V. Menil-Philippot and C. Thiriet (2017) Methods in Molecular Biology, 1528, 245-256.
- Nuclear dynamics at specific cell cycle stages in the slime mold Physarum polycephalum. C. Thiriet (2017) Nuclear Dynamics, 557-567.
- Histones H3 and H4 require their relevant amino-tails for replication-coupled chromatin assembly and efficient nuclear import in vivo.A. Ejlassi, V. Menil-Philippot, A. Galvani and C. Thiriet (2017) Scientific reports,7,3050.
- Complement C3 of the innate immune system secreted by muscle adipogenic cells promotes myogenic differentiation.T. Rouaud, N. Siami, T. Dupas, P. Gervier, M.-F. Gardahaut, G. Auda-Boucher and C. Thiriet (2017) Scientific reports, 7, 171
- Replication-coupled chromatin remodeling: an overview of disassembly and assembly of chromatin during replication. C. Duc and C. Thiriet (2021) Int J Mol Sci, 22(3), 1113
Thesis supervision and contact
Team: Epigenetics and chromatin dynamics.
Thesis Director: Dr Christophe Thiriet
Contact details: . – Tel : +33 2 51 12 57 64