In March 2024, the Senate of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) established the Priority Programme “EPIADAPT: Epigenomic adaptations of the developing neural chromatin” (SPP 2502). The programme is designed to run for six years. The present call invites proposals for the first three-year funding period.

Epigenetic chromatin modifications extend the repertoire of gene expression control mediated by a plethora of transcription factors. In development, epigenetic features can be transmitted from stem cells to differentiated progeny, modify cell fate decisions and establish an epigenetic memory of early lifetime experiences. The inheritance of epigenetic modifications emerges as a mechanism for how environmental signals leave traces in the chromatin. In central nervous system (CNS) development, epigenetics mediates adaptive changes in gene expression that accompany or drive cell state conversions. Because they can be stable or dynamic, triggered by environmental factors or genetic mutations/variations, altered epigenetic signatures contribute to human brain diseases with an origin in early life. To advance knowledge of the basic mechanisms of CNS development, the physiological responses during adaptation and their deregulation in developmental diseases and upon environmental insults, it is essential to investigate the molecular repertoire connecting mechanistically cellular features, transcriptional responses, epigenetic processes and environmental signals that together orchestrate CNS development.

Neuroepigenetics in particular advances basic knowledge of epigenetic gene expression control in the context of terminally differentiated neural cells with a long lifespan. It reveals how the neural chromatin integrates continuously changing conditions and exposes molecular mechanisms of brain cell specification and adaptation. It clarifies the setting in which chromatin regulation drives development and in which altered chromatin follows instructive environmental stimuli during cell state transitions. The focused research on the adaptive neural epigenome in the SPP EPIADAPT aims to explore the causalities of epigenomic adaptations during development by gaining an understanding of signalling to and from neural chromatin and by connecting adapted epigenomes to cellular outcomes. 

The objectives of the SPP EPIADAPT are:

1. to identify relevant biological mechanisms that mediate epigenomic adaptation through specific epigenetic writers, readers and erasers or remodellers; 
2. to explore molecular alterations in the different cellular compartments in the environment-epigenome signal transduction cascade active during development; and 
3. to characterise the dynamics of epigenomes in the developing central nervous system (CNS) linked to cellular phenotypes that define epigenetic barriers, permissive epigenomes and target specificity, ideally with single-cell or cell-type resolution.

The insights to be delivered within the funding period of the SPP 2502 concern molecular mechanisms that mediate the environmental contribution to an adapted neuroepigenome and control the plasticity of the neuroepigenome during progression of development. Projects aiming to explore epigenomic adaptations in the developing neural chromatin must imperatively include:

• Multiomic approaches to study epigenetic mechanisms (i.e., DNA methylation, histone modifications, chromatin accessibility, 3D genome organisation) in neural progenitors/stem cells, neurons and/or glia, in at least two different developmental states, to define adapted epigenomes, their cause and/or consequence; and
• Integrative data analyses advancing multiomics and multiscale views, with the aim to resolve mechanistic interdependencies of cell-specific epigenomes during developmental adaptation, ideally at single-cell or cell-type specific resolution; and
• Experimental efforts to understand mechanistically the plasticity of the neuroepigenome, to resolve whether or when the epigenome follows or allows development; and
• Data analysis and/or experimental attempts to resolve the connection between altered epigenomes and activity of signalling pathways; and 
• Relevant model systems restricted to humans or mice (iPSC-, ESC-derived neural progenitors, neurons, or glia, primary cell culture models with at least one CNS-derived cell type, brain organoids, human or mouse brain tissue).

In addition, to advance neuroepigenomic research further, at least one of the following inclusion criteria for participating in the SPP 2502 must be met:

• Exploration of regulatory mechanisms used by or controlling the enzymatic epigenetic machinery;
• Exploration of downstream effects of epigenetic enzymes in adapted or transient cell states in regard to canonical and non-canonical functions;
• Connection of the transmission of extracellular signals (classical signalling ligands; metabolic, synaptic or activity-related stimuli) to the developing neural epigenome;
• Crosstalk between different epigenetic processes;
• A strong but not exclusive methodological focus using and developing bioinformatics tools or precision genomic/epigenomic editing approaches with a high potential for overarching usage in different SPP 2502 projects.

We also encourage that proposed project proposals emphasise:

• Their collaborative character and potential as an added value of participating in a structured research programme; and
• their attempts and implementations to standardise and share datasets in the SPP 2502 consortium.

We discourage project proposals which:

• Focus on single epigenetic modifications or transcription factor binding without a clear reference to studying multimodal crosstalks to (further) epigenetic processes and addressing whether neural epigenetics is cause or consequence; 
• Are descriptive in nature, including characterisation of patient cohorts or large-scale sequencing studies, without mechanistic focus on deciphering and exploiting the adaptive epigenome of neural cells; 
• Focus exclusively on long non-coding RNAs, microRNAs or circular RNAs;
• Have a clinical focus (for example neurooncology) other than neurodevelopmental diseases, of which intellectual disability, autism spectrum disorders or schizophrenia fit the SPP´s layout;
• Include other model systems than human or mouse, and other cell types than those found mainly represented in the CNS.

Proposals must be written in English and submitted to the DFG by 11 December 2024. Please note that proposals can only be submitted via elan, the DFG’s electronic proposal processing system. To enter a new project within the existing Priority Programme, go to Proposal Submission – New Project/Draft Proposal – Priority Programmes and select “SPP 2502” from the current list of calls. 

When preparing your proposal, please review the programme guidelines (DFG form 50.05, section B) and follow the proposal preparation instructions (DFG form 54.01). These forms can either be downloaded from our website or accessed through the elan portal.

Applicants must be registered in elan prior to submitting a proposal to the DFG. If you have not yet registered, please note that you must do so by 27 November 2024 to submit a proposal under this call; registration requests received after this time cannot be considered. You will normally receive confirmation of your registration by the next working day. Note that you will be asked to select the appropriate Priority Programme call during both the registration and the proposal process.

Proposals will be reviewed by an international expert panel on the basis of the written documents. The envisaged start of funding is July 2025. 

The DFG strongly welcomes proposals from researchers of all genders and sexual identities, from different ethnic, cultural, religious, ideological or social backgrounds, from different career stages, types of universities and research institutions, and with disabilities or chronic illness. With regard to the subject-specific focus of this call, the DFG encourages female researchers in particular to submit proposals.

Further Information

More information on the Priority Programme is available at:

• https://uni-freiburg.de/spp2502

Online EPIADAPT symposium:
Interested applicants are invited to participate and discuss their project ideas at the online EPIADAPT symposium on 1 October 2024. Please register by sending an email until 25 September 2024 with a title and abstract of your 10-minute presentation to:

• spp2502@mail.uni-freiburg.de

The elan system can be accessed at:

• https://elan.dfg.de/en

DFG forms 50.05 and 54.01 can be downloaded at:

• www.dfg.de/formulare/50_05
• www.dfg.de/formulare/54_01

For scientific enquiries, please contact the Priority Programme coordinator:

• Professor Dr. Tanja Vogel, Albert-Ludwigs-Universität Freiburg, Institut für Anatomie und Zellbiologie, Anatomie II: Abteilung für Molekulare Embryologie, phone +49 761 203 5086, spp2502@mail.uni-freiburg.de

Questions on the DFG proposal process can be directed to:

• Programme contact: Dr. Thomas Baumgarten, phone +49 228 885-2456, thomas.baumgarten@dfg.de
• Administrative contact: Alexandra Schäpe, phone +49 228 885-3087, alexandra.schaepe@dfg.de