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H2020Doctoral network2020–2024

ENHPATHY · Molecular basis of human enhanceropathies

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2020-03-01 → 2024-02-29
EU contribution
€3,992,397
Participants
17
Scheme
MSCA-ITN

Lines connect the coordinator with its partners. CORDIS does not always give exact coordinates for projects before 2014. These points are placed at city or country level.

Results in brief

Molecular basis of human enhanceropathies

The primary goal of ENHPATHY was to provide ESRs with a multidisciplinary training program in which cutting-edge genomics approaches are combined with in vitro and in vivo disease models to enable understanding of the molecular basis of human enhanceropathies. Together with our private partners, we explored the translation of our molecular findings into new diagnostic and therapeutic avenues for patients. We divided our research program into 3 complementary scientific work packages (WP) to address the following key questions: WP1: How do genetic and epigenetic features control enhancer activity? We studied how transcription factor binding and genetic/epigenetic variation impact on enhancer activity. WP2: How do enhancers function within complex regulatory landscapes? We studied the mechanisms by which enhancers control gene regulation. WP3: How does enhancer deregulation impact human diseases? We identified disease-causing enhancer alterations and studied their pathological consequences. In parallel, we implemented an interdisciplinary and intersectoral program to train a future generation of highly skilled scientists in state-of-the-art research (WP4) and transferable skills (WP5), along with streamlined communication and outreach strategies through our specific STED and EnhancerInArt programs (WP6).

Data: CORDIS, © European Union

Project objective

Mutations within coding genes have traditionally been considered the major genetic cause of human disease. However, it is becoming increasingly clear that the genetic, structural and/or epigenetic disruption of enhancers and enhancer landscapes represent major etiological factors in numerous human diseases (i.e. enhanceropathies), ranging from rare congenital disorders to common diseases associated with ageing (e.g. cancer, diabetes). Although changes in enhancer activity are predicted to have broad pathological and therapeutic implications, we currently have a limited mechanistic understanding of human enhanceropathies. This reflects, at least partly, our still primitive and partial understanding of the mechanisms whereby enhancers can control gene expression. We hypothesize that enhancers are a diverse group of regulatory sequences that can utilize different mechanisms to control gene expression at the transcriptional and/or post-transcriptional level. Consequently, human enhanceropathies are likely to display an equally diverse molecular basis that, we believe, can only be uncovered using highly multidisciplinary systems biology approaches. Chiefly, elucidating the molecular basis of human enhanceropathies has far reaching translational implications, especially considering the pandemic proportions that some of these disorders are acquiring in recent years. Therefore, the major goal of the ENHPATHY network is to provide early-stage researchers with a multidisciplinary training in which cutting-edge genomic and genetic engineering approaches are ombined with various in vitro and in vivo disease models. Moreover, together with our private partners we aim at translating our molecular findings into new diagnostic and therapeutic strategies.

Original text from CORDIS.

Participants

  • INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · ParisCoordinatorFrance
  • ADVANCED BIODESIGN · Saint-PriestFrance
  • Annogen B.V. · AmsterdamNetherlands
  • ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE · LausanneSwitzerland
  • ELVESYS · PARISFrance
  • EUROPEAN MOLECULAR BIOLOGY LABORATORY · HeidelbergGermany
  • FUNDACIO CENTRE DE REGULACIO GENOMICA · BarcelonaSpain
  • GEN-X BV · AmsterdamCity levelNetherlands
  • ISTITUTO EUROPEO DI ONCOLOGIA SRL · MilanoItaly
  • KOBENHAVNS UNIVERSITET · KOBENHAVNDenmark
  • KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW · AMSTERDAMNetherlands
  • KUNGLIGA TEKNISKA HOEGSKOLAN · StockholmSweden
  • SYDDANSK UNIVERSITET · Odense MDenmark
  • UNIVERSIDAD DE CANTABRIA · SANTANDERSpain
  • UNIVERSITA HUMANITAS · PIEVE EMANUELEItaly
  • UNIWERSYTET WARSZAWSKI · WarszawaPoland
  • USTAV MOLEKULARNI GENETIKY AV CR V.V.I. · Praha 4Czechia

Links

Data: CORDIS, © European Union