Project Details
Projekt
Effects of nutritional stimuli on the epigenetic regulation of human cortical development
Applicant
Professorin Dr. Mareike Albert
Subject Area
Developmental Neurobiology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 563285578
The neocortex is instrumental for higher cognitive functions in humans. During neocortex development, epigenetic mechanisms regulate developmental gene expression programs, which are key for proper brain function later in life. Human brain development is highly protracted, and during this long period of development and maturation, the brain is sensitive to external environmental stimuli, leading to positive or negative outcomes. Environmental factors that signal to the neural chromatin may have profound impacts on the development of the neocortex, with potentially long-lasting effects on brain function. In this proposal, we aim to investigate the effects of maternal exposure to different nutritional stimuli on neural chromatin and cell fate. Maternal consumption of alcohol during pregnancy may result in foetal alcohol spectrum disorders (FASD), characterized by various impairments, such as microcephaly, developmental delay, intellectual disability and psychiatric problems. On the other hand, peri-conceptual intake of folic acid benefits human development, reducing the risk of neural tube closure defects, affecting the spine and brain. While the mechanisms of the effect of alcohol exposure and folic acid supplementation on cortical development remain largely unknown, there is evidence from animal models that epigenetic regulation is involved. This project aims to systematically investigate a large set of histone modifications with single cell resolution using Epi-CyTOF in human cortical organoids exposed to alcohol and following folic acid supplementation. Moreover, cell type-specific epigenomes will identify the genes that are sensitive to epigenetic adaptations induced by nutritional stimuli. Single cell RNA-sequencing will reveal how alcohol and folic acid affect neurodevelopment at the cellular and molecular level. Functional studies using epigenetic inhibitors and epigenome editing will provide mechanistic insight and will help explore the potential compensation of neurodevelopmental outcomes after neurotoxin exposure. Taken together, this project is expected to shed light on how the neural chromatin integrates environmental stimuli provided by maternal nutrition and on how the altered epigenomes affect neural cell fate in the human developing neocortex.
DFG Programme
Priority Programmes
