ICF: Epigenomics Rare Diseases Node

Epigenomics and epigenetics are the studies on how the activity of genes are controlled. The EpiGenRare node will coordinate research in epigenomics of rare diseases. This is important because >100 rare epigenetic diseases are known, and collectively they represent a large number of patients with rare dieases. Epigenetic diseases remain challenging to discover, diagnose, understand and treat. Furthermore, epigenomic studies that have the ability to study changes across all of the DNA in patients are important even for those rare diseases that are not traditionally seen as epigenetic diseases.

This multi-disciplinary node team (investigators, partners and collaborators) includes experts in relevant disciplines, industry, and patient support groups and encompasses institutions across the UK and investigators at different career stages. Our team builds on substantial existing infrastructure, funding and track records that will enable us to tackle the challenges in the area.

In our networking activities we will undertake a scoping survey to generate a list of individuals and institutions relevant for this field, and invite them to be members of EpiGenRare. Between years two and five, we will host two multi-disciplinary EpiGenRare conferences. Over the course of five years, we will arrange at least four EpiRare meetups on the side-lines of other scientific conferences. We will organise research or educational sessions at other conferences where epigenomics is relevant, but traditionally has not been a focus for those meetings. We will prioritise networking with other nodes in the Rare Disease Platform through brainstorming sessions.

For co-ordination we will organise a virtual EpiGenRare (for investigators and partners) kick-off meeting followed by an Introductory EpiGenRare meeting (for all members). Thereafter, we will hold EpiGenRare Operational meetings every 4 months. Individual research project team meetings will be organised at appropriate frequencies, minimum once a month. We will also form the EpiGenRare Advisory Board (including scientific and clinical leaders, industry and patient and public representatives) that will meet annually.

We propose three enabling projects: (1) To generate a resource linking patients' genomic and epigenomic data which can be used by other researchers. (2) To perform preliminary studies in animal models to test if similar treatment approach could be used for multiple epigenetic diseases that share clinical features and biological mechanisms. (3) Generate a resource of well studied human cell models for large scale drug testing in epigenetic diseases. Additionally, we have put in place ideas for future projects with our collaborators and several other nodes in the UK Rare Disease Platform.

As part of our patient and public involvement (PPI) program we will build upon our existing relationships with various relevant patient-family support groups. Patient support groups will be part of the advisory board and will participate in driving the networking activities and the research and collaboration agenda. We will bring together several patient support groups at different stages of development. With patient support groups we will co-develop patient information resources, organise family education days and work together to develop evidence-based management guidelines for epigenetic disorders.

In conclusion, the EpiGenRare node is timely and addresses several unmet needs and will help to enhance the performance of the UK Rare Disease Platform. Our networking activities and PPI program will lead to establishing a national collaborative multi-disciplinary network for epigenomics of rare diseases that would be an international reference on research in rare epigenetic disorders for clinicians, researchers, patient support groups and policy-leaders. Our current and future research projects will allow us to accelarate diagnosis and treatments for epigenetic disorders.

The EpiGenRare node will coordinate research in the domain of epigenomics of rare diseases. Our multi-disciplinary team has expertise in epigenomics, epigenetic mechanisms, human genetics, animal and human pluripotent cell models. We will establish a national collaborative multi-disciplinary network that would be an international reference on research in rare epigenetic disorders for clinicians, researchers, patient support groups and policy-leaders. We will provide training opportunities for early career researchers and deliver networking opportunities by hosting EpiGenRare conferences to bring together fundamental and clinician scientists, clinicians, technical and methodological experts, and patient groups, members of other nodes and international experts.

Our initial research focus will be on rare diseases with mutations in genes encoding chromatin modifiers and multi-locus imprinting disorders (MLID). Collectively, this group of epigenetic disorders are relatively common with major unmet clinical need due to their mechanistic basis being poorly understood, and progress in their management being hampered by the lack of known biomarkers and therapies. To address these challenges, we will (1) create a linked resource of patient samples to decipher the genome-epigenome relationships in imprinting disorders; (2) explore the possibility of therapeutic convergence in chromatinopathies using mouse models of biologically and clinically overlapping diseases, and (3) lay the ground for large-scale high throughput drug screening for therapies using human stem cell models for chromatinopathies.

These projects will enable technology evaluation and complete data integration for the development of diagnostic, prognostic and therapeutic biomarkers from patient samples, provide evidence for convergent mechanisms and preliminary data for translational and pre-clinical projects and generate sharable resources (mouse and human models, technological approaches and data).