Personal profile

Biography

 

After studying biology at five universities in Germany and the UK, I completed my Masters degree in primatology at Wuerzburg University and then moved to Cambridge to study behavioural epigenetics for my PhD, which I obtained in 2004. I held a Senior Rouse Ball Scholarship at Trinity College, Cambridge and then moved to Manchester to work with Jason Wolf on quantitative genetics and genomic imprinting in rodent models for a 3-year BBSRC postdoc. I was awarded two Emmy Noether Fellowships by the German Science Foundation as well as a NERC fellowship to work on indirect genetic and maternal effects in rodent models at Manchester before becoming a lecturer in 2011.

Over the years I have held several external and internal roles. I am grant panel member for NERC and academic advisor for the Commonwealth Scholarship Service, and have acted as external assessor for UCD, Ireland. I have been Associate Editor for Frontiers in Genetics, BMC Genetics, BMC Evolution, and BMC Ecology and Evolution. I also organized symposia for ISBE at Cornell and Tuebingen, and organized the 18th International meeting of the Complex Trait Consortium in Manchester in 2021.

I am the longest-serving Senate member of the University's Board of Governors (since 2012), and presently member of the University's Finance Committee, Examination Board, and the Staffing Committee in the past. I am also a member of the FBMH Faculty Committee, and Chair of the School Board for the School of Biological Sciences. I am also Senior Postgraduate Tutor.

As part of social responsibility, I have been a Director and Trustee of the Portico Library in Manchester since 2012, and am Chair of its Finance Committee. I was also Vice-Chair of the Portico Trust until 2020. Occasionally, I give public lectures on evolutionary biology and human evolution.

Research interests

What are the mechanisms by which environmental factors experienced during early development lead to altered developmental trajectories and adult phenotypes? To answer this fundamental question, we are investigating the role of epigenetic mechanisms as a mediator of environmental effects experienced during early development, and associated effects at the gene expression and protein level that lead to changes in adult phenotypes. 

Our research uses rodent model systems, but we are also using data from human populations. In our laboratory, we utilize both genome-wide and targeted approaches, which are complemented by bioinformatics and statistical modelling. 

Epigenetic mechanisms of responses to maternal immune activation during early development on neurodevelopment and adult behaviour

One of the fundamental questions in basic disease research is how stressors experienced during critical periods influence the development of adult disease. In particular, stressors experienced during pregnancy have been shown to impact on the propensity to develop cognitive disorders in offspring. What are the mechanisms underlying such effects? To answer this fundamental question, we are linking placental morphological development to offspring traits, achieved by combining experimental studies in a rodent model system with evaluation of placental morphological development, parent-offspring behavioural interactions, cognitive and behavioural analyses. This comprehensive phenotype profiling is combined with histological analyses of relevant brain parts (such as the prefrontal cortex) and molecular array and epigenomic studies. Here, we use both genome-wide approaches such as RRBS, ChIP-seq and RNA-seq and targeted approaches such as qPCR, ChIP-qPCR, but also a variety of protein assays. This is complemented by a bioinformatics component to unravel the biological pathways and genetic networks of known candidates for placental function and associated behavioural impairments to establish a comprehensive picture of how the exposure to maternal inflammation during early development causes altered neurodevelopment and behaviour.

Collaborators: Joanna Neill, Jocelyn Glazier, Michael Harte, John Gigg, Christopher Murgatroyd

 

Epigenetic mechanisms of phenotypic plasticity and predictive adaptive responses

Phenotypic plasticity is the ability of a given genotype to produce different phenotypes depending on the environmental conditions experienced (during development). What are the underlying mechanisms of such plasticity? For example, we seek to establish fitness and developmental consequences of experiencing changes from early to late environment, and the underlying mechanisms of these changes reflected in differences in the epigenome and associated changes at the gene expression and protein level. We are using both genome-wide assays such as RRBS and RNAseq as well as targeted approaches focussing on specific candidate genes, e.g. pyrosequencing and qPCR. Pathway and other bioinformatics analyses help us to understand the functional consequences of expression or epigenetic changes. Our experimental designs are specific to our questions and range from aphid-plant systems to manipulation of developmental conditions in live-bearing cockroaches.

Collaborators: Christopher Murgatroyd

 

 

Genetic, epigenetic and environmental predictors of adverse adult outcomes

How do genetic predisposition and environmental factors interact to determine trajectories of development and adverse adult behavioural and cognitive outcomes? Our group has worked on linking genetic variants identified in a genetic model to human populations thus establishing novel candidates underlying cognitive disorders. We are also interested in human population data from longitudinal studies such as ALSPAC and identifying genetic and epigenetic variants associated with adverse behavioural outcomes in adolescence and adulthood.

Collaborators: David Ashbrook, Tarani Chandola, Stephanie Cahill

 

 

Indirect genetic effects, family conflicts and coadaptation

Our group has worked on complex trait genetics and indirect genetic effects with a focus on establishing the genetic variants and associated functional pathways underlying parent offspring and sibling interactions. We used the recombinant inbred mouse population BXD as a model in cross-fostering designs and investigated indirect genetic effects that impact on development and behaviour, in the context of parent-offspring conflict over resource allocation. For example, our studies have identified several allelic variants in the offspring genome that affect the quality of maternal behaviour, and thus indirectly offspring fitness. This occurs most likely through affecting specific offspring behaviours that elicit a maternal response.

Collaborators: David Ashbrook, Robert Williams

 

 

Systems genetics, genomic imprinting and maternal effects

Using quantitative genetic mapping approaches, we have worked with James Cheverud (Chicago) and Jason Wolf (Bath) on separating epigenetic and genetic effects on developmental traits in rodent models. We were also interested in maternal genetic effects that may cause phenotypic patterns similar to those caused by genomic imprinting (parent-of-origin dependent gene expression).   

Collaborators: James Cheverud, Jason Wolf

 

   

Teaching

BIOL10642 Africa Field Course in Animal Behaviour
BIOL30471 Advances in Behavioural Ecology

My group

 

 

 

Isabel Faulkner

I am a current PhD student here at the University of Manchester in the Hager lab. I started my academic journey at Newcastle University, where I studied for a BSc in Pharmacology. I found the course fascinating and was particularly interested in studying how drugs are being repurposed to treat a wide variety of psychiatric diseases, for which current treatments are largely ineffective. This led me to study for a Masters degree in Neuroscience, at the University of Bristol. Here I utilised in vivo approaches to investigate the neural mechanisms of psychedelic drugs used to treat addiction.

 

My project here at Manchester aims to expand upon the work carried out in the lab. I will use the well validated model of neurodevelopmental disease in order to further investigate how stressors experienced prenatally can predispose to neurodevelopmental disorders such as schizophrenia later in life. Along this developmental timeline I will investigate and profile novel treatments for their efficacy in this model, and to try and elucidate their molecular mechanisms. I hope that this research will help contribute to our understanding of neurodevelopmental disease, and will address the lack of effective treatments.

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Francesca McEwan

For my undergraduate degree, I studied Neuroscience with Industrial Experience at The University of Manchester, during which, I undertook my placement year working as a research trainee at Stockholm University, where my work was focused on researching the actions of the neuropeptide, ion transport peptide (ITP), in the Drosophila melanogaster nervous system.  Following the obtainment of my BSc, I worked as a research technician for two years at The University of Manchester, where I gained further molecular and in vivo research skills.

My PhD project is funded by the BBSRC and aims to establish how epigenetic mechanisms may contribute to the aetiology of neurodevelopmental disorders (NDDs). I am specifically interested in how maternal immune activation contributes to an increased risk of developing NDDs, such as schizophrenia, in the offspring. I therefore plan to use a multidisciplinary approach in order to map how epigenetic changes across the developmental timeline impact brain and behavioural phenotype.

Publications

Gigg, J., McEwan, F., Smausz, R., Neill, J., Harte, M. (2019). Synaptic biomarker reduction and impaired cognition in the sub-chronic PCP mouse model for schizophrenia. Journal of Psychopharmacology. 34: 115-124.

Rachael Pajak

 

Khairiah Almushri

 

 

 

 

 Alumni (postgraduate research)

  • Stephanie Cahil, PhD 2024
  • Jarred Lorusso, PhD 2023
  • Rebecca Woods, PhD, 2023
  • Jessica Brown, PhD, 2023
  • Mhd Shadi Khudr, Postdoc (2018-2023)
  • Zhe Yang (Scott) Yim, PhD, 2023
  • Heidi Eltaher, visiting researcher 2022-23
  • Hawa Jahan, PhD, 2023
  • Harry Potter, PhD, 2021
  • Amy Grime, MNeuro, 2020
  • Mariana Villalba de La Pena, PhD, 2020
  • Hager Kowash, PhD, 2020
  • Grace Revill, MNeuro, 2019
  • Veysi Pikobulu, MPhil 2019
  • Samuel Purkiss, MPhil, 2019
  • Christopher Cook, PhD, 2017
  • Megan McLaughlin, MNeuro, 2016
  • Christina Stanley, PhD, 2015
  • Naorin Sharmin, PhD, 2015
  • David Ashbrook, PhD, 2015
  • David Pettifer, MRes, 2015
  • Beatrice Gini, PhD, 2014
  • Barbora Trubenova, PhD, 2013
  • Charlotte Cox, MPhil, 2012
  • Madoka Satoh, Japan Exchange student, 2012
  • Gareth Muirhead, MRes, 2012
  • Michael Crompton, MRes, 2011
  • Erasmia Konstantinou, MRes 2011
  • Sophie Lyst, MSc, 2011
  • Ali Rezaee, MRes, 2011

 

 

Social responsibility

I am a Director of the Portico Library, and Chair of its Finance Committee.

The Portico Library is a 214-year-old independent subscription library in Manchester City Centre. Still housed in its original Georgian building on Mosley Street, it is now open free to the public six days a week for an eclectic calendar of exhibitions and events, complementing the unique collection of books, archives and illustrations spanning over 450 years. Previously a members’ only institution with associates including John Dalton, Peter Mark Roget, Elizabeth Gaskell, Emmeline Pankhurst, Robert Peel, and Richard Cobden, all visitors can now enjoy a meal or drink in the cafe from Monday to Saturday and participate in diverse outreach and engagement programmes including the prestigious Portico Prize.

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being
  • SDG 5 - Gender Equality
  • SDG 11 - Sustainable Cities and Communities
  • SDG 15 - Life on Land

Research Beacons, Institutes and Platforms

  • Christabel Pankhurst Institute

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