EpiStressNet: A biosocial systems approach to understanding the epigenetic embedding of social stress responses.

Lead Research Organisation: University of Sheffield
Department Name: Biomedical Science

Abstract

The social environments in which we live provide daily challenges that affect how we think and feel, influencing our behaviour and sense of well-being. However, it is far from clear exactly how these experiences affect us at a physical level. Recent research in biology has discovered molecules that are found in all of our cells, which interpret our experiences by switching genes on or off in particular cell types. These molecules, or "epigenetic" mechanisms, bind to DNA and control gene activity, which in turn change the functions of our cells, tissues and organs, and so affect what we think, feel and do. We are beginning to understand that these epigenetic mechanisms are modified by factors that also affect our health, and recent evidence indicates that social stress is one such factor. Societies in which there is a bigger gap between rich and poor, such as the UK, also have bigger, more stressful social and health inequalities. Good evidence suggests that the social stress caused by social inequality leads to ill-health and that this link may involve epigenetic mechanisms. This project aims to build a network of biological and social scientists to explore how social stress causes epigenetic changes which affect biology and behaviour. To address this problem, we will establish a team with wide-ranging expertise in investigating (a) the physical effects of stress on gene activity in the brain and the body, (b) the impacts of social inequality on health, and (c) how we think about the way our experiences get under our skin to shape behaviour and well-being. This team of social science, public health and biology researchers, will develop and carry out novel shared projects. We will hold discussion meetings to consider new biological and sociological ideas together, and share new discoveries that will help to explain how social stresses exert their effects on the brain and the rest of the body, and the roles of epigenetics in these processes. We will also meet with industrial, government and health service professionals, to consider the potential impacts of our research for their work, and engage with the general public more broadly to discuss the wider implications of this research for society.

Planned Impact

Social and Economic Benefits: the huge costs of inequality to good social relations, health, educational attainment and social mobility are well-known. It is less well-understood how best to develop solutions to these problems that will produce measurable, durable improvements. Understanding the biosocial mechanisms that mediate the effects of inequality will help to develop an evidence-base that will be useful in formulating solutions and monitoring their effectiveness. Better knowledge about how social stressors erode health and well-being through modification of epigenetic processes will offer opportunities to create a knowledge-base and toolkit for preventing, ameliorating and/or potentially reversing risks to health. Biotechnology companies with an interest in developing such technologies would directly benefit from the new knowledge produced by this project. The new knowledge would also then be useful to government agencies and health services to either reduce the prevalence of risk factors in the social environment or introduce new experiences that enrich social and environmental quality and offset existing risks. The activities and outputs of the network will therefore be of benefit to government agencies, health services, as well as news media, charities and civil society groups concerned with the adverse social impacts of economic inequality, and the search for social policies that could ameliorate the disadvantages conferred by deprivation. There is extensive evidence showing that gradients of inequality and their corrosive effects on societal and individual well-being are increasing. Better public understanding of the consequences of policy choices for social and health inequalities, together with an appreciation of the evidence base about how social causes produce social consequences via changes to biological processes, will benefit democratically-empowered citizenries wanting to understand the facts of inequality, debate the policy alternatives and collectively determine their future social directions. Thus, in addition to engaging with the types of organizations described above, it will be imperative to engage with the general public to disseminate new knowledge about the types of social stresses that epigenetically embed risks to ill-health, and debate the policy options for achieving behaviour change at the individual and societal levels that could alter the long-term risks of ill-health over the life-course.

Building new capacity for interdisciplinary biosocial research: the broad aim of the proposal is to understand the biological mechanisms through which the social stressors that are characteristic drivers of social inequality become biologically embedded and contribute to health inequalities. We will create an interdisciplinary network with strengths in the analysis of biological mechanisms using both model organisms and human population studies, together with social science expertise in instrumental, empirical evidence-based analysis, and strengths in conceptualization of social phenomena and consideration of their implications for public policy. The network will build capacity for biosocial systems analysis by integrating this wide range of specialist expertise, and involve ECRs in all activities to develop the next generation of interdisciplinary researchers. The research network will carry out small-scale pilot studies and hold interdisciplinary workshops, to test hypotheses and develop new interdisciplinary strategies for understanding how social stress responses become epigenetically embedded. Through facilitating the convergence of relevant biological and social science disciplines, the network will enhance UK capacity to develop a robust evidence-base for effective policy responses to social and health inequalities. We will promote the impact of the network's wide range of capabilities in these areas through a series of Impact Workshops and a programme of Public Engagement activities.

Publications


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Cunliffe VT (2015) Experience-sensitive epigenetic mechanisms, developmental plasticity, and the biological embedding of chronic disease risk. in Wiley interdisciplinary reviews. Systems biology and medicine
Cunliffe VT (2016) Histone modifications in zebrafish development. in Methods in cell biology
Vineis P (2017) Epigenetic memory in response to environmental stressors. in FASEB journal : official publication of the Federation of American Societies for Experimental Biology
 
Description We have identified genomic CpG sites that exhibit differential methylation in the brain of wild-type and nr3c1 mutant zebrafish. These loci are within or nearby genes that are also differentially transcribed in the brain of wild-type and nr3c1 mutant zebrafish. The genes we have identified are likely to be regulated by the stress hormone cortisol via interactions of cortisol-bound Glucocorticoid Receptor with DNA sequences lying near to or that include the differentially methylated CpGs that we have identified.

Non-specialist audience: we have identified regions of the genome whose activity in the zebrafish brain is regulated by the stress hormone cortisol. We think that these sequences are a "signature" of stress in the brain and that similar signatures may exist in humans, particularly people exposed to high levels of social and behavioural stress, and that these changes could affect their thoughts, feelings and behaviour. We would like to see whether we can detect similar changes in human blood cells from poor and socially disadvantaged communities exposed to high levels of stress.
Exploitation Route We would like to see whether we can detect similar changes in the DNA isolated from blood cells of people from poor and socially disadvantaged communities exposed to high levels of stress. These changes might be markers of social stress and disadvantage and their reversal might provide biological markers of the effectiveness of any health/social interventions to improve health or ameliorate social adversity.
Sectors Healthcare
 
Description Medical Research Council Discovery Medicine North Doctoral Training Partnership
Amount £84,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 10/2016 
End 03/2020
 
Description EpiStressNet Glasgow mid-project Research Meeting 
Organisation University of Glasgow
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution I co-organised the mid-term research review and discussion meeting for the EpiStressNet network, held at the University of Glasgow and hosted by Professor Paul Shiels on 1 and 2 December 2016.
Collaborator Contribution A series of structured research discussion and presentations were delivered over the course of 2 days.
Impact Grant applications submitted: 1. Wellcome Trust Seed Award in Science. Principal Applicant:Dr David Lehane, University of Sheffield. Co-Applicant, Dr Vincent Cunliffe, University of Sheffield. Title:Linking the stress of migration to TB reactivation: feasibility of a combined psycho-social and molecular mechanism study within deprived and immigrant communities.
Start Year 2015
 
Description EpiStressNet research network - Kick-Off Meeting 
Organisation Imperial College London (ICL)
Department Faculty of Medicine
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution I am the Principal Investigator on the grant that is funding the EpiStressNet network activities. A PDRA in my lab, Dr Helen Eachus, is carrying out some important pilot studies to validate come of the key concepts underpinning EpiStressNet. The Network Co-ordinator, John Paul Ashton, is also a member of my research team. I organised the inaugural Kick-Off meeting of the EpiStressNet research network, attended by members of my research team, including the Network Co-Ordinator, John Paul Ashton, who helped me to organise the meeting. The meeting was held in Sheffield on 3 March 2016. I will continue in this role for the duration of EpiStressNet's existence.
Collaborator Contribution Network members participated in the meeting by providing talks and contributing to discussions.
Impact The EpiStressNet inaugural research meeting was held on 3 March 2016, in Sheffield. I organised the meeting, which was attended by 20 researchers, most of whom are existing members of EpiStressNet, as well as a small number of invited speakers and other participants with relevant interests, whom I have recruited to the network since it was first established.
Start Year 2015
 
Description EpiStressNet research network - Kick-Off Meeting 
Organisation Imperial College London (ICL)
Department School of Public Health
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution I am the Principal Investigator on the grant that is funding the EpiStressNet network activities. A PDRA in my lab, Dr Helen Eachus, is carrying out some important pilot studies to validate come of the key concepts underpinning EpiStressNet. The Network Co-ordinator, John Paul Ashton, is also a member of my research team. I organised the inaugural Kick-Off meeting of the EpiStressNet research network, attended by members of my research team, including the Network Co-Ordinator, John Paul Ashton, who helped me to organise the meeting. The meeting was held in Sheffield on 3 March 2016. I will continue in this role for the duration of EpiStressNet's existence.
Collaborator Contribution Network members participated in the meeting by providing talks and contributing to discussions.
Impact The EpiStressNet inaugural research meeting was held on 3 March 2016, in Sheffield. I organised the meeting, which was attended by 20 researchers, most of whom are existing members of EpiStressNet, as well as a small number of invited speakers and other participants with relevant interests, whom I have recruited to the network since it was first established.
Start Year 2015
 
Description EpiStressNet research network - Kick-Off Meeting 
Organisation Sheffield Children's NHS Foundation Trust
Department Sheffield Children's Hospital
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Hospitals 
PI Contribution I am the Principal Investigator on the grant that is funding the EpiStressNet network activities. A PDRA in my lab, Dr Helen Eachus, is carrying out some important pilot studies to validate come of the key concepts underpinning EpiStressNet. The Network Co-ordinator, John Paul Ashton, is also a member of my research team. I organised the inaugural Kick-Off meeting of the EpiStressNet research network, attended by members of my research team, including the Network Co-Ordinator, John Paul Ashton, who helped me to organise the meeting. The meeting was held in Sheffield on 3 March 2016. I will continue in this role for the duration of EpiStressNet's existence.
Collaborator Contribution Network members participated in the meeting by providing talks and contributing to discussions.
Impact The EpiStressNet inaugural research meeting was held on 3 March 2016, in Sheffield. I organised the meeting, which was attended by 20 researchers, most of whom are existing members of EpiStressNet, as well as a small number of invited speakers and other participants with relevant interests, whom I have recruited to the network since it was first established.
Start Year 2015
 
Description EpiStressNet research network - Kick-Off Meeting 
Organisation The Johannes Gutenberg University of Mainz
Country Germany, Federal Republic of 
Sector Academic/University 
PI Contribution I am the Principal Investigator on the grant that is funding the EpiStressNet network activities. A PDRA in my lab, Dr Helen Eachus, is carrying out some important pilot studies to validate come of the key concepts underpinning EpiStressNet. The Network Co-ordinator, John Paul Ashton, is also a member of my research team. I organised the inaugural Kick-Off meeting of the EpiStressNet research network, attended by members of my research team, including the Network Co-Ordinator, John Paul Ashton, who helped me to organise the meeting. The meeting was held in Sheffield on 3 March 2016. I will continue in this role for the duration of EpiStressNet's existence.
Collaborator Contribution Network members participated in the meeting by providing talks and contributing to discussions.
Impact The EpiStressNet inaugural research meeting was held on 3 March 2016, in Sheffield. I organised the meeting, which was attended by 20 researchers, most of whom are existing members of EpiStressNet, as well as a small number of invited speakers and other participants with relevant interests, whom I have recruited to the network since it was first established.
Start Year 2015
 
Description EpiStressNet research network - Kick-Off Meeting 
Organisation University of Glasgow
Department Beatson Institute for Cancer Research
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Charity/Non Profit 
PI Contribution I am the Principal Investigator on the grant that is funding the EpiStressNet network activities. A PDRA in my lab, Dr Helen Eachus, is carrying out some important pilot studies to validate come of the key concepts underpinning EpiStressNet. The Network Co-ordinator, John Paul Ashton, is also a member of my research team. I organised the inaugural Kick-Off meeting of the EpiStressNet research network, attended by members of my research team, including the Network Co-Ordinator, John Paul Ashton, who helped me to organise the meeting. The meeting was held in Sheffield on 3 March 2016. I will continue in this role for the duration of EpiStressNet's existence.
Collaborator Contribution Network members participated in the meeting by providing talks and contributing to discussions.
Impact The EpiStressNet inaugural research meeting was held on 3 March 2016, in Sheffield. I organised the meeting, which was attended by 20 researchers, most of whom are existing members of EpiStressNet, as well as a small number of invited speakers and other participants with relevant interests, whom I have recruited to the network since it was first established.
Start Year 2015
 
Description EpiStressNet research network - Kick-Off Meeting 
Organisation University of Glasgow
Department College of Medical, Veterinary and Life Sciences
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution I am the Principal Investigator on the grant that is funding the EpiStressNet network activities. A PDRA in my lab, Dr Helen Eachus, is carrying out some important pilot studies to validate come of the key concepts underpinning EpiStressNet. The Network Co-ordinator, John Paul Ashton, is also a member of my research team. I organised the inaugural Kick-Off meeting of the EpiStressNet research network, attended by members of my research team, including the Network Co-Ordinator, John Paul Ashton, who helped me to organise the meeting. The meeting was held in Sheffield on 3 March 2016. I will continue in this role for the duration of EpiStressNet's existence.
Collaborator Contribution Network members participated in the meeting by providing talks and contributing to discussions.
Impact The EpiStressNet inaugural research meeting was held on 3 March 2016, in Sheffield. I organised the meeting, which was attended by 20 researchers, most of whom are existing members of EpiStressNet, as well as a small number of invited speakers and other participants with relevant interests, whom I have recruited to the network since it was first established.
Start Year 2015
 
Description EpiStressNet research network - Kick-Off Meeting 
Organisation University of Lausanne
Department Institute of Social and Preventive Medicine (IUMSP)
Country Switzerland, Swiss Confederation 
Sector Academic/University 
PI Contribution I am the Principal Investigator on the grant that is funding the EpiStressNet network activities. A PDRA in my lab, Dr Helen Eachus, is carrying out some important pilot studies to validate come of the key concepts underpinning EpiStressNet. The Network Co-ordinator, John Paul Ashton, is also a member of my research team. I organised the inaugural Kick-Off meeting of the EpiStressNet research network, attended by members of my research team, including the Network Co-Ordinator, John Paul Ashton, who helped me to organise the meeting. The meeting was held in Sheffield on 3 March 2016. I will continue in this role for the duration of EpiStressNet's existence.
Collaborator Contribution Network members participated in the meeting by providing talks and contributing to discussions.
Impact The EpiStressNet inaugural research meeting was held on 3 March 2016, in Sheffield. I organised the meeting, which was attended by 20 researchers, most of whom are existing members of EpiStressNet, as well as a small number of invited speakers and other participants with relevant interests, whom I have recruited to the network since it was first established.
Start Year 2015
 
Description EpiStressNet research network - Kick-Off Meeting 
Organisation University of Leicester
Department School of Biology
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution I am the Principal Investigator on the grant that is funding the EpiStressNet network activities. A PDRA in my lab, Dr Helen Eachus, is carrying out some important pilot studies to validate come of the key concepts underpinning EpiStressNet. The Network Co-ordinator, John Paul Ashton, is also a member of my research team. I organised the inaugural Kick-Off meeting of the EpiStressNet research network, attended by members of my research team, including the Network Co-Ordinator, John Paul Ashton, who helped me to organise the meeting. The meeting was held in Sheffield on 3 March 2016. I will continue in this role for the duration of EpiStressNet's existence.
Collaborator Contribution Network members participated in the meeting by providing talks and contributing to discussions.
Impact The EpiStressNet inaugural research meeting was held on 3 March 2016, in Sheffield. I organised the meeting, which was attended by 20 researchers, most of whom are existing members of EpiStressNet, as well as a small number of invited speakers and other participants with relevant interests, whom I have recruited to the network since it was first established.
Start Year 2015
 
Description EpiStressNet research network - Kick-Off Meeting 
Organisation University of Sheffield
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution I am the Principal Investigator on the grant that is funding the EpiStressNet network activities. A PDRA in my lab, Dr Helen Eachus, is carrying out some important pilot studies to validate come of the key concepts underpinning EpiStressNet. The Network Co-ordinator, John Paul Ashton, is also a member of my research team. I organised the inaugural Kick-Off meeting of the EpiStressNet research network, attended by members of my research team, including the Network Co-Ordinator, John Paul Ashton, who helped me to organise the meeting. The meeting was held in Sheffield on 3 March 2016. I will continue in this role for the duration of EpiStressNet's existence.
Collaborator Contribution Network members participated in the meeting by providing talks and contributing to discussions.
Impact The EpiStressNet inaugural research meeting was held on 3 March 2016, in Sheffield. I organised the meeting, which was attended by 20 researchers, most of whom are existing members of EpiStressNet, as well as a small number of invited speakers and other participants with relevant interests, whom I have recruited to the network since it was first established.
Start Year 2015
 
Description EpiStressNet research network - Kick-Off Meeting 
Organisation University of Sheffield
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution I am the Principal Investigator on the grant that is funding the EpiStressNet network activities. A PDRA in my lab, Dr Helen Eachus, is carrying out some important pilot studies to validate come of the key concepts underpinning EpiStressNet. The Network Co-ordinator, John Paul Ashton, is also a member of my research team. I organised the inaugural Kick-Off meeting of the EpiStressNet research network, attended by members of my research team, including the Network Co-Ordinator, John Paul Ashton, who helped me to organise the meeting. The meeting was held in Sheffield on 3 March 2016. I will continue in this role for the duration of EpiStressNet's existence.
Collaborator Contribution Network members participated in the meeting by providing talks and contributing to discussions.
Impact The EpiStressNet inaugural research meeting was held on 3 March 2016, in Sheffield. I organised the meeting, which was attended by 20 researchers, most of whom are existing members of EpiStressNet, as well as a small number of invited speakers and other participants with relevant interests, whom I have recruited to the network since it was first established.
Start Year 2015
 
Description EpiStressNet research network - Kick-Off Meeting 
Organisation University of Sheffield
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution I am the Principal Investigator on the grant that is funding the EpiStressNet network activities. A PDRA in my lab, Dr Helen Eachus, is carrying out some important pilot studies to validate come of the key concepts underpinning EpiStressNet. The Network Co-ordinator, John Paul Ashton, is also a member of my research team. I organised the inaugural Kick-Off meeting of the EpiStressNet research network, attended by members of my research team, including the Network Co-Ordinator, John Paul Ashton, who helped me to organise the meeting. The meeting was held in Sheffield on 3 March 2016. I will continue in this role for the duration of EpiStressNet's existence.
Collaborator Contribution Network members participated in the meeting by providing talks and contributing to discussions.
Impact The EpiStressNet inaugural research meeting was held on 3 March 2016, in Sheffield. I organised the meeting, which was attended by 20 researchers, most of whom are existing members of EpiStressNet, as well as a small number of invited speakers and other participants with relevant interests, whom I have recruited to the network since it was first established.
Start Year 2015
 
Description EpiStressNet research network - Kick-Off Meeting 
Organisation University of Sheffield
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution I am the Principal Investigator on the grant that is funding the EpiStressNet network activities. A PDRA in my lab, Dr Helen Eachus, is carrying out some important pilot studies to validate come of the key concepts underpinning EpiStressNet. The Network Co-ordinator, John Paul Ashton, is also a member of my research team. I organised the inaugural Kick-Off meeting of the EpiStressNet research network, attended by members of my research team, including the Network Co-Ordinator, John Paul Ashton, who helped me to organise the meeting. The meeting was held in Sheffield on 3 March 2016. I will continue in this role for the duration of EpiStressNet's existence.
Collaborator Contribution Network members participated in the meeting by providing talks and contributing to discussions.
Impact The EpiStressNet inaugural research meeting was held on 3 March 2016, in Sheffield. I organised the meeting, which was attended by 20 researchers, most of whom are existing members of EpiStressNet, as well as a small number of invited speakers and other participants with relevant interests, whom I have recruited to the network since it was first established.
Start Year 2015
 
Description EpiStressNet research network - Kick-Off Meeting 
Organisation University of Strathclyde
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Academic/University 
PI Contribution I am the Principal Investigator on the grant that is funding the EpiStressNet network activities. A PDRA in my lab, Dr Helen Eachus, is carrying out some important pilot studies to validate come of the key concepts underpinning EpiStressNet. The Network Co-ordinator, John Paul Ashton, is also a member of my research team. I organised the inaugural Kick-Off meeting of the EpiStressNet research network, attended by members of my research team, including the Network Co-Ordinator, John Paul Ashton, who helped me to organise the meeting. The meeting was held in Sheffield on 3 March 2016. I will continue in this role for the duration of EpiStressNet's existence.
Collaborator Contribution Network members participated in the meeting by providing talks and contributing to discussions.
Impact The EpiStressNet inaugural research meeting was held on 3 March 2016, in Sheffield. I organised the meeting, which was attended by 20 researchers, most of whom are existing members of EpiStressNet, as well as a small number of invited speakers and other participants with relevant interests, whom I have recruited to the network since it was first established.
Start Year 2015