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Impact of Early life MetaBolic and psychosocial strEss on susceptibility to mental Disorders; from converging epigenetic signatures to novel targets for therapeutic intervention

Impact of Early life MetaBolic and psychosocial strEss on susceptibility to mental Disorders; from converging epigenetic signatures to novel targets for therapeutic intervention 2019-2022
Acronym: EMBED
Project director: Robi Tacutu
External website: full link

Starting 01.06.2019, the Institute of Biochemistry of the Romanian Academy is implementing the EMBED project, funded by UEFISCDI (contract 103, from 01.06.2019), through the ERA-NET COFUND-NEURON III grant call. The project aims to assess the shared molecular links between pre- and post-natal, metabolic and psychosocial stress, and the risks of depression later in life, and its duration will be 36 months.

Project summary

Nearly 40% of the EU population each year suffers from a mental disorder. Adverse experiences early in life can produce important physiological changes, which become embedded biological traces leading to increased vulnerability for later depression. There is now robust evidence indicating that early metabolic challenges impinge upon energy balance regulatory systems, which, in many cases, overlap with stress-response systems. EMBED will identify informative DNA methylation differences associated with prenatal psychological and metabolic stressors in genes that are relevant for mood disorders. These will be related to shared biomarkers to define common biological substrates between early life stress and maternal obesity for prevention and treatment. We will also determine whether intervention strategies can reverse such epigenetic marks and related biomarkers. The relationship between DNA methylation pattern in human peripheral samples (cord blood) and brain will be studied in animal models and brain post-mortem samples from depressive patients. EMBED brings together leading researchers with complementary expertise to exploit existing clinical data sets, including biomaterial collections from previous collaborative proposals, that will be analyzed in an original and innovative way to study the role of different, but often co-occurring, adverse prenatal conditions on individual risk/resilience to develop mental disorders in adulthood. This research may lead not only to a better understanding of the risk architecture of major psychiatric disorders, but could also enable preventive measures in risk populations, new diagnostics and, potentially, therapeutic approaches since, in contrast to genetic variations, epigenetic effects on the transcriptome may be reversed, also in adulthood.

 

Obejctives

The primary objectives of this work are to:

  1. Assess shared epigenetic mechanisms of maternal stress and maternal obesity through DNA methylation analysis and discovery in children born to stressed or obese mothers as well as adult post-mortem brains from people whose mothers were stressed or obese;
  2. Test shared biological mechanisms mediating psychological stress and metabolic stress through metabolome and transcriptome analysis in two mother/infant cohorts;
  3. Define the epigenetic signature of disease reversibility;
  4. Delineate epigenetic signatures predicting high risk of depression for early prevention; and
  5. Discover novel genes that respond both to maternal stress and maternal obesity.

As secondary objectives, the project aims to also:

  1. Characterize the stability of methylation profiles of candidate genes between birth and later points in life; and
  2. Establish the level of correspondence in methylation profiles of genes between brain and peripheral white blood cells at birth and later in life.

 

Funding

This project is funded by UEFISCDI (contract 103, from 01.06.2019), through the ERA-NET COFUND-NEURON III (2018) grant call. For more details, please visit: https://uefiscdi.gov.ro/neuron-cofund

Robi Tacutu, Ph.D.
Robi Tacutu, Ph.D.

Group leader

A thorough, analytical and curiosity-driven scientist, with a multidisciplinary background in biology and computer science, Robi received his BSc in computer science from the University Politehnica Bucharest, and his MSc in biochemistry and molecular biology from the University of Bucharest. He has a long-term commitment and interest in the field of biogerontology (since 2005) and received his PhD in 2013 from the Ben-Gurion University of the Negev, in the lab of Prof. Vadim Fraifeld. His thesis was on an ageing-related topic: studying the relationships between aging and age-related diseases with the use of bioinformatics and network biology approaches, and More...

Anton Yurievich Kulaga, M.Phil.
Anton Yurievich Kulaga, M.Phil.

Bioinformatics research assistant

Anton has a formal background in international management and economics (Kyiv National Economic University, 2003 - 2008, M.A. with honors). Being passionate about programming since high school, he worked for many years as More...

Catalin-Florentin Ion
Catalin-Florentin Ion

Technician, Front-end developer

With a B.Sc. in Communication Sciences, biochim joined the Computational Biology of Aging Group in order to aesthetically shape all of our web resources and interactions with the outside work. Aside from his formal educati More...

Dan Mihaila, Mr.
Dan Mihaila, Mr.

Research assistant, Web developer

Dan Mihaila is a researcher in the Institute of Biochemistry of the Romanian Academy. Dan is currently working in Systems Biology of Aging in the Bioinformatics & Structural Biochemistry.

Gabriela Bunu, Mrs.
Gabriela Bunu, Mrs.

PhD student, Bioinformatics research assistant

Gabriela is a bioinformatics researcher at the Institute of Biochemistry, focussing on curation for aging-related data, analysis of large screen datasets and network-based analyses. She has a multidisciplinary background, More...

Project Coordinator

Francesca Cirulli

Francesca Cirulli

Center for Behavioral Sciences and Mental Health, Istituto Superiore di Sanità ISS

Viale Regina Elena 299, 00161, Rome, Italy

francesca.cirulli@iss.it

 

Consortium partners

Marcella Rietschel

Marcella Rietschel

Department of Genetic Epidemiology in Psychiatry. Central Institute of Mental Health CIMH

J 5, 68159, Mannheim, Germany

marcella.rietschel@zi-mannheim.de

 
Moshe Szyf

Moshe Szyf

Department of Pharmacology and Therapeutics, McGill University McGU

McIntyre Medical Building 3655 Prom. Sir William Osle, QC H3G 0B1, Montreal, Canada

moshe.szyf@mcgill.ca

 
Robi Tacutu

Robi Tacutu

Department of Bioinformatics and Structural Biochemistry, Institute of Biochemistry, Romanian Academy RomAcad

Splaiul Independentei 296, 060031 Bucharest, Romania

robi.tacutu@gmail.com

Up to this moment there have been no publications resulting from this project.