Scientific Focus – SPP2502 EPIADAPT

Adaptive neural epigenomes

Adaptation processes bearing a temporal component are the foundation of a developing organism and developmental processes often associate with changes in the epigenetic landscape.

It is therefore not surprising that epigenetic mechanisms are involved in different neurodevelopmental processes including control of proliferation and differentiation of neuronal stem cells, neuronal migration, cell survival, morphological maturation, and synapse formation/maturation.

Cell autonomous and non-autonomous communication pathways that impinge on epigenetic chromatin modification are far from being understood mechanistically and will be explored in SPP2502 projects.

Furthermore, recent research crystallizes that CNS diseases have an epigenetic layer, including neurodevelopmental diseases. Epigenetic processes not only affect neurodevelopmental disorders during development. But as a consequence of complex genome-environment interactions they leave traces surfacing in adulthood. A prime example is schizophrenia. The number of such diseases with a recognized epigenetic layer is raising steadily, further selected examples include epilepsy autism and depression.

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Signals mediating epigenetic adaptation in neural genomes

Signals controlling or impacting the epigenetic machinery are likely, but largely unexplored. While signaling cascades stimulated by membrane receptors that interpret the local environment are well studied in CNS development, function and disease, we still face a surprising lack of knowledge about how such signaling events shape and adapt the epigenome.

Research integrating signaling and epigenetic mechanisms, decoding the up- and downstream molecular events of chromatin modification in neuronal development, provides the experimental basis for exploring the adaptive capacity of the brain, and at the same time advancing our understanding of neurodevelopmental diseases.

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Technical advancements for studying epigenetics in neural cell transition and adaptation

To address open mechanistic questions related to cell state transitions and adaptation processes in neuroepigenetics, the SPP2502 will integrate groups that advance and allow bioinformatics analyses. SPP2502 research will profit on recent technological advancements, especially in four different areas: (i) development of high throughput sequencing methods alongside respective bioinformatics tools, (ii) single-cell sequencing technology that combines transcriptomic and epigenomic analyses, (iii) genome-editing approaches conferring local viewpoint on epigenetic adaptation, and (iv) advanced cellular model systems that allow studying the human CNS, interactions in heterologous cellular systems, and employing reprogramming strategies.

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