SYSCID - A Systems medicine approach to chronic inflammatory diseases
The international consortium of the European research project SYSCID (“A systems medicine approach to chronic inflammatory disease“) aims to develop a personalised medicine approach for inflammatory bowel disease, rheumatoid arthritis and systemic lupus erythematosus. The project coordinated by Kiel University in Germany (CAU) receives a total funding of 14.4 million Euros for a period of five years. Academic and industry partners from nine different countries join forces to achieve the ambitious goals of the project which has started at the beginning of 2017.
With a lifetime prevalence of over ten percent in the EU, chronic inflammatory disease (CID) poses a major health care burden to modern society. SYSCID will focus on three major CID (inflammatory bowel disease, systemic lupus erythematodes and rheumatoid arthritis) to identify a common set of unifying mechanisms that contribute to their pathogenesis.
The SYSCID consortium aims to develop a systems medicine approach for predictions in chronic inflammatory diseases (CID). The overall goal is to create a prediction framework for disease outcome to guide therapy decisions on an individual patient level enabling the choice of the right therapy at the right time. Furthermore, the consortium targets new therapy approaches by “reprogramming” disease through epigenome editing.
In summary, SYSCID pursues the following strategic goals:
- To identify shared and unique “core disease signatures” of the CIDs inflammatory bowel disease (IBD), rheumatoid arthritis (RA) and systemic lupus, which are associated with the disease state and independent of temporal variation to help fast and unequivocal diagnosis
- To understand mechanisms of response/non-response to specific treatments using multidimensional, dynamic molecular data from CID patients
- To generate predictive models of disease outcome to guide therapy decisions on an individual patient basis
- To foster the development of solid biomarkers and models as stratification in future long-term clinical trials
- To investigate new causative therapies by editing the epigenome code in specific immune cells
SYSCID will use dense clinical sampling and molecular phenotyping to analyse longitudinal patient cohorts and obtain a deeper understanding of the immunological network changes associated with response and non-response to current treatment regimes. Unlike current therapeutic interventions which mainly alleviate the symptoms, SYSCID aims to develop a therapeutic strategy that will eventually offer a first causal therapy. The consortium targets new therapy approaches by ‘reprogramming’ disease through epigenome editing. Assuming that the development and course of a disease are related to long-term epigenetic alterations, it makes sense to target the very root of the disease.
The SYSCID approach combines several biomarker layers from the epigenome to the microbiome, but also aims to investigate more sophisticated tools, such as single cell analysis. New epigenetic markers could be more significant than inflammation markers in the blood which have been used so far. As these ‘traditional’ markers also increase in patients with a common cold or elevated temperature, they cannot always be allocated clearly.
SYSCID will build on previous and ongoing research activities by partners and international initiatives such as IHEC with the aim of exploiting already collected and established patient data and enabling their utilisation for the development of new clinical applications.
For further information, please visit: http://syscid.eu/
Launched in January 2017, the EU-funded project MultipleMS brings together universities and companies across 11 European countries and the US to tailor the development and application of therapies to the individual Multiple Sclerosis (MS) patient. Following this mission, the project will build on the large amount of datasets already generated within IHEC.
MS is an immune-mediated disease and a leading cause of non-traumatic disability in young adults in Europe, affecting over 2 million persons worldwide. MS is a highly heterogeneous disease and a cure for MS is not yet available. As the result of current treatments varies strongly from patient to patient, predicting the specific beneficial treatment for each patient would improve disease management.
The main objective of MultipleMS is to develop novel personalised medicine approaches for MS patients. This goal is timely, not only because there is an urgent need for precision management of MS but also because necessary knowledge, methodologies and vast multi-layer data resources are now available.
MultipleMS will identify a combination of evidence-based selection of clinical, biological, and lifestyle features that can predict the clinical course, stratify patients based on their risk and the therapeutic response to the existing drugs in a real-world setting, and to gain in-depth knowledge of distinct pathogenic pathways to allow identification of targets for novel treatments.
Moreover, stratified patient populations will be identified utilizing unprecedented large cohorts rich in genetic, lifestyle, clinical, imaging and DMT response data. Publically available large scale ‘multi- omics’ data, in particular high-resolution maps of immune cells, in combination with ‘multi-omics’ data from MS patients, will empower identification of biological pathways underlying stratified patient populations. MultipleMS will further validate these pathways in a prospective observational study, prioritize novel therapeutic targets and initiate a drug development program.
For further information, please visit: http://www.multiplems.eu/
BLUEPRINT - A BLUEPRINT of Haematopoietic Epigenomes
The project proposal from the BLUEPRINT consortium, consisting of 41 leading European universities, research institutes and industry entrepreneurs, was selected for funding early 2011. The project officially started on October 1, 2011 and will run for 4,5 year. BLUEPRINT has an overall budget of 39.4 M€ for which it receives 30 M€ funding from the European Commission.
Overall project goal
Blueprint aims to generate at least 100 reference epigenomes and studying them to advance and exploit knowledge of the underlying biological processes and mechanisms in health and disease. BLUEPRINT will focus on distinct types of haematopoietic cells from healthy individuals and on their malignant leukaemic counterparts.
The BLUEPRINT reference epigenome will entail analysis of 19 ‘marks’. A IHEC CORE set (DNAme, H3K4me3, H3K4me1, H3K9me3, H3K27me3, H3K27ac, H3K36me3, RNA-seq, DNaseI hypersensitivity) and a ‘BLUEPRINT set’ (H3K79me3, H3K9/14ac, H4K20me3, H4pan/H4K16ac, H2AZ-ac, H2AZ, p300 and RNA PolII).
- Mature blood cells from cord blood and adult blood
- Cord blood precursor cells
- CD14+CD16-monocytes derived cells from both Cord Blood and Adult
- Cord cells derived cells
- Normal B-cells
- Normal T-cells
- B-cell neoplasms
- T-cell neoplasms
- Myeloid leukaemias
- Autoimmune disease
- Mouse C57BL6J, C3H/HeJ, CAST/EiJ (CD14+CD16- monocytes and CD4 (naïve) T cells)
For further details see: www.blueprint-epigenome.eu/index.cfm?p=7BCEDA45-EC73-3496-2C823D929DD423DB
The core activity (Research Area 1) of BLUEPRINT will be to generate the 100 reference epigenomes.
Other activities include:
- Identification and validation of epigenetic markers and exploration of the epigenome interplay with genetic variation: address the causes and consequences of epigenetic variation and utilize this knowledge for improved diagnostics of human diseases. Where appropriate, this will be complemented by studies involving relevant animal models.
- Development and validation of novel technology for high throughput epigenome mapping: improve epigenome analysis, resolution and efficiency with a focus on DNA methylation and miniaturizing Chromatin Immunoprecipitation (ChIP).
- Identification of new compounds interfering with the regulators of epigenetic profiles: definition of epigenome relevant drug targets involved in cancer and development of small molecule approaches for their inhibition.
- Training, networking, communication and outreach: topical workshops will be organized and a lab exchange program will be set up. Furthermore, collaboration will be established with related networks in Europe and worldwide.
The involvement of innovative companies is expected to energize epigenomic research in the private sector by the development of smart technologies for better diagnostic tests and by identifying new targets for compounds. Thus the results of the BLUEPRINT project may lead to targeted diagnostics, new treatments and preventive measures for specific diseases in individual patients, an approach known as 'personalised medicine'.