Studying enhancer function to understand human disease

Enhancers play an important role in determining how genes are expressed in different cells in the body. The goal of the ENHPATHY consortium is to identify these enhancers and how they regulate gene expression. Knowledge about enhancer function may eventually lead to new treatments against diseases associated with enhancer dysfunction. 

 
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Please cite if you share this article : Spicuglia, S., Ferrer, J. (2023). ‘Studying enhancer function to understand human disease’, EU Research, Winter 2023 vol. (37), pp. 10 – 12.

 

On June 15th, our 15 students will face the challenge of presenting their Enhancer in art project to a lay audience. One condition: not to exceed 90 seconds!

 
About Enhancer in art: Enhancer in art is a science/art program that offers an artist the unique opportunity to become an actor in a European scientific program by creating an original artwork in collaboration with one of our PhD students.
 
We would like to thank all the artists who have agreed to take part in this programme:

Tejeswini Padma Iwan Vaandrager ( https://lnkd.in/evWv3aDe ) Dr Dimple Devadas FRSA Annelie Mollbrink PhD Alyona Buglakova ( https://lnkd.in/ezQEetVy ) Laura K. Holm Alessandro Ventura Kochamon Manprasatkul Anastasia Stankevich ( https://lnkd.in/e86jf7mJ ) Ondrej Mistrik ( https://lnkd.in/egT63x6D ) Minh Hoang ( https://lnkd.in/evyMMdWk ) Zijun Feng ( https://lnkd.in/evv5xdhS ) Ekaterina Onufrienko ( https://lnkd.in/ePa76buV )
 
About Enhpathy:
Enhpathy is a multidisciplinary scientific consortium created in the framework of the Marie Sklodowska-Curie Actions (MSCA-Doctoral Networks), bringing together 15 academic and 9 non-academic European organizations in the continuum of basic, translational and clinical research on enhancers and related diseases.
 
To view our PhD students’ profiles and to contact them: https://www.enhpathy.eu/team/
 
Follow Enhpathy on Twitter: https://twitter.com/enhpathy_H2020

 

Enhancers play a central role in the spatiotemporal control of gene expression and tend to work in a cell-type-specific manner. In addition, they are suggested to be major contributors to phenotypic variation, evolution and disease. There is growing evidence that enhancer dysfunction due to genetic, structural or epigenetic mechanisms contributes to a broad range of human diseases referred to as enhanceropathies. Such mechanisms often underlie the susceptibility to common diseases, but can also play a direct causal role in cancer or Mendelian diseases. Despite the recent gain of insights into enhancer biology and function, we still have a limited ability to predict how enhancer dysfunction impacts gene expression.

In this Perspective review published in the Nature Structural & Molecular Biology journal, the ENHPATHY researchers discuss the major challenges that need to be overcome when studying the role of enhancers in disease etiology and highlight opportunities and directions for future studies, aiming to disentangle the molecular basis of enhanceropathies.

Read more

 

New publication by Alberich-Jorda M and Sladana Kosanovic in EMBO reports.

Chronic inflammation represents a major threat to human health since long-term systemic inflammation is known to affect distinct tissues and organs. Recently, solid evidence demonstrated that chronic inflammation affects hematopoiesis; however, how chronic inflammation affects hematopoietic stem cells (HSCs) on the mechanistic level is poorly understood. Here, we employ a mouse model of chronic multifocal osteomyelitis (CMO) to assess the effects of a spontaneously developed inflammatory condition on HSCs. We demonstrate that hematopoietic and nonhematopoietic compartments in CMO BM contribute to HSC expansion and impair their function. Remarkably, our results suggest that the typical features of murine multifocal osteomyelitis and the HSC phenotype are mechanistically decoupled. We show that the CMO environment imprints a myeloid gene signature and imposes a pro-inflammatory profile on HSCs. We identify IL-6 and the Jak/Stat3 signaling pathway as critical mediators. However, while IL-6 and Stat3 blockage reduce HSC numbers in CMO mice, only inhibition of Stat3 activity significantly rescues their fitness. Our data emphasize the detrimental effects of chronic inflammation on stem cell function, opening new venues for treatment.

Link on the publication

 

 

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In all mammals, the cellular operation responsible for the maintenance of homeostasis, specifically of all the physiological balances ensuring the vital functions of an organism, is dictated by the reading of information carefully preserved in the genetic heritage or DNA. The expression of a gene that will code for one or more proteins of interest is therefore a strategic step, controlled by the presence on this DNA of regulatory sequences, which in the event of malfunction, can cause the occurrence of serious genetic pathologies, such as inflammation or auto-immune diseases.

 

Listed in two distinct families according to their locations near or far from the genes that they regulate, researchers speak of promoters or enhancers, respectively. These sequences are scrutinized by the scientific community in an attempt to arrive at a better understanding of the complexity of their modes of action. The latest work from a research team within the TAGC laboratory (Theories and Approaches to Genomic Complexity, Inserm/AMU), led by Dr. Spicuglia and published in the journal Nature Communications have recently shed new light on the role of a particular family of promoters called Epromoter that are involved in gene regulation, but this time, without particular location criteria.

Read more

 

The new  EMBO workshop co-organized by Álvaro Rada-IglesiasSalvatore Spicuglia and Susanne Mandrup and involving 6 Enhpathy’s students starts today. Please find more information about this event on the EMBO Workshop’s website.

About the Workshop

Due to the current COVID-19 emergency this workshop might need to be cancelled depending on national and local recommendations. In order to give both organizers and participants more time before making any decision, the registration and payment deadlines have been extended. In case of cancellation, registration fees will be reimbursed. We also recommend all invited speakers and participants to purchase their flight tickets with a cancellation insurance

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 represent major etiological factors in numerous human diseases (i.e. enhanceropathies), ranging from rare congenital disorders to common diseases associated with ageing and lifestyle (e.g. cancer, diabetes). Although changes in enhancer activity are predicted to have broad pathological and therapeutic implications, we currently have a limited understanding of human enhanceropathies. This reflects, at least partly, our still primitive and partial understanding of the mechanisms whereby enhancers can control gene expression. To overcome these limitations, this workshop will bring together experts in enhancer biology, gene regulation and medical genetics that, during three days, will present their latest work. Our invited speakers and participants will discuss the multidisciplinary approaches required to investigate enhancer function as well as debate about the role of enhancers in fundamental biological processes (e.g. embryonic development, evolution) and in the etiology of human disorders. Ultimately, the goal of this EMBO Workshop will be to provide a complete view of how a deep and systems-level understanding of enhancer function can facilitate elucidating the molecular basis of human enhanceropathies.

 

One position is available for a 2-year PhD program funded by the Marie Sklodowska-Curie Innovative Training Network (ITN) ENHPATHY.

Candidates with bioinformatics, genomics and/or molecular and cellular biology backgrounds are encouraged to apply. The host lab offers opportunities to extend this period for one or two years to complete a full PhD thesis in the Centre for Genomics Regulation and Universitat Pompeu Fabra.

Application deadline: September 30th

Organization: Centre for genomic regulation

More information on this link 

Download the full description

 

 

The new  EMBO workshop co-organized by Álvaro Rada-IglesiasSalvatore Spicuglia and Susanne Mandrup is now open for registration –> register here. 

About the Workshop

Due to the current COVID-19 emergency this workshop might need to be cancelled depending on national and local recommendations. In order to give both organizers and participants more time before making any decision, the registration and payment deadlines have been extended. In case of cancellation, registration fees will be reimbursed. We also recommend all invited speakers and participants to purchase their flight tickets with a cancellation insurance

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 represent major etiological factors in numerous human diseases (i.e. enhanceropathies), ranging from rare congenital disorders to common diseases associated with ageing and lifestyle (e.g. cancer, diabetes). Although changes in enhancer activity are predicted to have broad pathological and therapeutic implications, we currently have a limited understanding of human enhanceropathies. This reflects, at least partly, our still primitive and partial understanding of the mechanisms whereby enhancers can control gene expression. To overcome these limitations, this workshop will bring together experts in enhancer biology, gene regulation and medical genetics that, during three days, will present their latest work. Our invited speakers and participants will discuss the multidisciplinary approaches required to investigate enhancer function as well as debate about the role of enhancers in fundamental biological processes (e.g. embryonic development, evolution) and in the etiology of human disorders. Ultimately, the goal of this EMBO Workshop will be to provide a complete view of how a deep and systems-level understanding of enhancer function can facilitate elucidating the molecular basis of human enhanceropathies.

 

ENHPATHY is a multidisciplinary science consortium created in the frame of the Marie Sklodowska-Curie actions (MSCA)-ITN-ETN European Training Networks call and regrouping 12 academic and 3 non-academic European organisations in the continuum of basic, translational and clinical research on enhancers and associated diseases.

ESR applications to ENHPATHY ‘s training program : all applications should be made using the recruitment form to be published from March 15 to April 16, 2020 (https://www.enhpathy.eu/recruitment/).

Candidates with bioinformatics, genomics and/or molecular and cellular biology backgrounds are encouraged to apply.

We are pleased to announce that the EnhPathy ITN H2020 PhD call will open on March 15th 2020. EnhPathy will be recruiting 15 PhD students to start their training program within the September-December 2020 period.

Please check the Nature careers ad on this link

ENHPATHY is a multidisciplinary science consortium created in the frame of the Marie Sklodowska-Curie actions (MSCA)-ITN-ETN European Training Networks call and regrouping 12 academic and 3 non-academic European organisations in the continuum of basic, translational and clinical research on enhancers and associated diseases.

All applications should be made using the recruitment form to be published from March 15 to April 16, 2020 (https://www.enhpathy.eu/recruitment/).

Candidates with bioinformatics, genomics and/or molecular and cellular biology backgrounds are encouraged to apply.

Read full press release

The new  EMBO workshop co-organized by Álvaro Rada-IglesiasSalvatore Spicuglia and Susanne Mandrup is now open for registration –> https://bit.ly/2qoO4yC 

About the workshop : 
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 represent major etiological factors in numerous human diseases (i.e. enhanceropathies), ranging from rare congenital disorders to common diseases associated with ageing and lifestyle (e.g. cancer, diabetes). Although changes in enhancer activity are predicted to have broad pathological and therapeutic implications, we currently have a limited understanding of human enhanceropathies. This reflects, at least partly, our still primitive and partial understanding of the mechanisms whereby enhancers can control gene expression. To overcome these limitations, this workshop will bring together experts in enhancer biology, gene regulation and medical genetics that, during three days, will present their latest work. Our invited speakers and participants will discuss the multidisciplinary approaches required to investigate enhancer function as well as debate about the role of enhancers in fundamental biological processes (e.g. embryonic development, evolution) and in the etiology of human disorders. Ultimately, the goal of this EMBO Workshop will be to provide a complete view of how a deep and systems-level understanding of enhancer function can facilitate elucidating the molecular basis of human enhanceropathies.

Brainstorming meeting gathering Enhpathy members – Marseille.

List of beneficiaries :

Salvatore Spicuglia (Coordinator), Institut Nationale pour la Santé et la Recherche Médicale (INSERM), France

Alvaro Rada-Iglesias (Vice Coordinator), University of Cantabria (UNICAN), Spain

Meritxell Alberich-Jorda, Institute of Molecular Genetics of the AS CR (IMG), Czech Republic

Robin Andersson, University of Copenhagen (UCPH), Denmark

Bart Deplancke, Swiss Federal Institute of Technology Lausanne (EPFL), Switzerland

Jorge Ferrer, Centre for Genomic Regulation (CRG), Spain

Wouter de Laat, Royal Netherlands Academy of Arts and Sciences (KNAW), The Netherlands

Susanne Mandrup, University of Southern Denmark (SDU), Denmark

Gioacchino Natoli,  European Institute of Oncology (IEO), Italy

Dariusz Plewczynski, University of Warsaw (UoW), Poland

Pelin Sahlén, Royal Institute of Technology (KTH), Sweden

Judith Zaugg, European Molecular Biology Laboratory (EMBL), Germany

Joris van Arensbergen, Gen-X B.V. (Gen-X), The Netherlands

Julia Sepulveda Diaz, ELVESYS SAS (Elvesys), France

Mileidys Perez Alea, Advances BioDesign (ABD), France

List of partnering organisations :

Christian Thirion (Sirion), Germany

Gonzalo R. Ordóñez (Dreamgenics), Spain

Remi Terranova (Novartis Pharma AG), Switzerland

James B. Meigs, Alisa Manning (TOPMed), United States of America

Thomas Lemberger (GLWF, EMBO Press), Germany

J.C. Fitzsimons (Leadership Sculptor), Germany

Jean M. Grangeon (KOM Agency), France

Jacques van Helden (Institut Français de Bioinformatique)

Alain Arnaudet (La Friche Belle de Mai), France

Jorge Ferrer (UPF, Universitat Pompeu Fabra), Spain

Meritxel Alberich-Jorda (CUNI, Univerzita Karlova, Charles University), Czech Republic

Wouter de Laat (UU, Universiteit Utrecht), Netherlands