Project Reference: TRG27-ZOO-ML1

Project title: Epigenetic regulation of critical period-plasticity during nervous system development

Project outline

Critical periods are important tuning phases during late stages of brain, marked by heighted plasticity. These are also vulnerable to disturbances, which can cause permanent maladjustment; in humans, thought to be responsible for several psychiatric conditions and forms of epilepsy. How it is that critical period-induced errors cannot be corrected later on has remained a mystery.

Having developed an insect model for studying critical periods, the fruit fly (Drosophila) embryo, we recently discovered a new perspective, which points to metabolic signals and metabolic reprogramming as central to critical periods (Sobrido-Cameán et al., 2025). This project will follow up on preliminary findings that implicate epigenetic modifiers as instrumental in turning transient signals during the critical period into permanent changes in gene expression.

Specifically, you will use novel genetic tools for cell type-specific Chromatin-DamID-seq that we created in collaboration with the Jelle van den Ameele lab, who are experts in mitochondrial biology and Chromatin-DamID-seq. The aim is to identify signatures of normal critical periods vs those caused by perturbation; then to study how these epigenetic modifications lead to lasting changes in the expression of metabolic genes. This would open the door to developing approaches for re-opening critical periods, so that mal-adjusted brains are given the opportunity to re-adjust toward more optimal configurations. 

References:

Sobrido-Cameán D et al. (2025). Mitochondrial ROS and HIF-1α signaling mediate synaptic plasticity in the critical period. PLoS Biol. 2025 Aug 13;23(8):e3003338. doi: 10.1371/journal.pbio.3003338. 

van den Ameele J et al. (2024).  Targeted DamID detects cell-type specific histone modifications in vivo. bioRxiv (pre-print);  doi: https://doi.org/10.1101/2024.04.11.589050

Principal Supervisor

Professor Matthias Landgraf

Email address: ml10006@cam.ac.uk

Department / Partner Institute: Zoology

Website: https://www.zoo.cam.ac.uk/people/matthias-landgraf

BBSRC strategic theme

Understanding the rules of life