Reinmar Hager

Reinmar Hager, MSc, PhD

Dr

 https://orcid.org/0000-0002-6692-5669
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Personal profile

Biography

Postdoctoral Appointments
2018 Senior Lecturer, The University of Manchester
2011 Lecturer, The University of Manchester
2008 NERC Research Fellow, The University of Manchester
2005 Postdoctoral Research Associate, The University of Manchester
2004 Postdoctoral Research Assistant, University of Cambridge

Education
2004 PhD, Trinity College, University of Cambridge
1999 MSc (Diplom-Biologe), University of Würzburg
1996-1997 Undergraduate studies in biology, University of Edinburgh
1993-1996 Undergraduate studies in economics, psychology, law and biology, Universities of Kassel, Munich and Stuttgart

Awards & Distinctions
2009-2014 DFG Emmy Noether Group Leader, LMU Munich (declined)
2009         World Health Summit, Berlin, invitation
2008-2011 NERC Research Fellowship
2005-2007 DFG Emmy Noether Research Fellowship
2002-2003 Senior Rouse Ball Scholarship, Trinity College

External Committees
2021-present Commonwealth Scholarship Service - Academic Advisor
2018 External Assessor, University College Dublin, Ireland
2016-present NERC Panel C and IOF panel member
2012-present NERC Peer Review College

Internal Committees and appointments
2021-present University Finance Committee
2021-present Chair, School Board, School of Biological Sciences                                           
2019-present Senior Postgraduate Tutor
2017-present Board of Governors
2017-present Senate
2018-2021 University Staffing Committee
2008-2020 General Assembly
2016-2019 School Lead for International Postgraduate Research
2012-2015 Board of Governors
2012-2015 Senate
2014-2015 University Staffing Committee
2011-2016 Postgraduate Tutor
 
Dissemination
Plenaries: 6 international plenaries
Seminars: 32 invited University seminars, 63 conference contributions
Media: research featured in numerous international media, e.g. Der Standard, Der Tagespiegel, Nature, Noorderlicht, Science, Westdeutsche Rundfunk, BBC News

Editorial Boards
2021-present  BMC Ecology and Evolutionary Biology, Associate Editor
2018-2021     BMC Evolutionary Biology, Associate Editor
2014-2018     BMC Genetics, Associate Editor
2010-2014     Frontiers in Genetics of Complex Traits, Review Editor

Social Responsibility
2012-present  Director: The Portico Library, Manchester
2021-present  Chair, Finance and Resources Committee, The Portico Library, Manchester
2014-2020      Vice Chair: The Portico Trust Charity, Manchester

 

Key Publications

Ashbrook DG, Gini B, Hager R. 2016. Genetic variation in offspring indirectly influences the quality of maternal behaviour in mice. eLife, 10.7554/eLife.11814

Hager R, Lu L, Rosen GD, Williams RW. 2012. Genetic architecture supports mosaic brain evolution and independent brain-body regulation. Nature Communications, 3, 1079.

Nonacs P, Hager R. 2011. The past, present and future of reproductive skew theory and experiments. Biological Reviews, 86, 271-298.

Cheverud JM, Hager R, Roseman C, Fawcett G, Wang B, Wolf JB. 2008. Genomic imprinting effects on adult body composition in mice. PNAS, 105, 4253-4258.

Wolf JB, Cheverud JM, Roseman C, Hager R. 2008. Genome-wide analysis reveals a complex pattern of genomic imprinting in mice. PLoS Genetics, 4, e1000091.

Wolf JB, Hager R. 2006. A maternal-offspring coadaptation theory for the evolution of genomic imprinting. PLoS Biology, 4(12)

Hager R, Johnstone RA. 2003. The genetic basis of family conflict resolution in mice. Nature, 421, 533-535.

Roulin A, Hager R. 2003. Indiscriminate nursing in communal breeders: A role for genomic imprinting. Ecology Letters 6, 165-166

Book Hager R, Jones CB. 2009. Reproductive Skew. Cambridge UP.

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 focuses on both evolutionary and developmental research questions, which we investigate experimentally in insect and 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 (current PhD student)

 

 

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

 

   

Overview

Our research utilizes experimental and bioinformatics approaches to investigate key questions in evolutionary biology, behavioural ecology and complex trait and biomedical research.

We seek to understand how genetic, epigenetic and environmental factors interact and contribute to trait variation. We use different model systems ranging from invertebrate to mammalian models (aphids, daphnia, roaches, mouse, rat, human) and plants, and investigate traits from the molecular level (e.g. expression and epigenetic profiles), tissue level (e.g. brain) through to neuroanatomical and behavioural traits in whole organisms.

 

Teaching

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

My group

Dr Mhd Shadi KhudrMhd Shadi Khudr

icon Postdoctoral researcher

Biography

I obtained my BSc in Biological Sciences from Damascus University, Syria in 2002 followed by my postgraduate diploma in Zoology from the same university in 2003. I then completed my PhD at Manchester in 2012. I worked at The University of Manchester between 2012-2014 as a postdoc. In 2014, I was appointed a two-year visiting postdoctoral fellow at the Freie Universität Berlin, Germany.

I am an evolutionary ecologist working at crossroads of ecology, evolution, genetics and agronomy; with keen interest in the influence of genetic variation on and species interactions across GxG and GxGxE contexts.

A focus research has been on Community Genetics as a platform for ecological interactions, where a significant portion of the environment of a focal species is differentially defined by the expressed genomes of other interacting species. Using a quantitative genetic experimental design I have quantified a differential impact of a genotype on the behaviour of another hetero-specific genotype. As such, I provide some of the clearest evidence on the emergence of shared (extended) phenotypes between natural enemies liable to co-evolutionary arms-race. I am particularly interested in the interplay between ecological forces (such as competition between spatially separated organisms, parasitoidism and predation) and community genetic effects.

I also conducted research on epiphytic bromeliads and their associated faunal communities in the Meso-American tropics. Afterwards, I investigated the influence of varying levels of heavy metal pollution on the fitness and parental care in the burying beetle Nicrophorus vespilloides. Furthermore, I have worked on the co-evolutionary dynamics of intraguild interactions on mono- and multi-varietal backgrounds and in the light of soil-community feedback and ecological disturbance.

My current projects aim to untangle the genetics and epigenetics components of plastic responses to an array of environmental stimuli in terrestrial and aquatic systems. I predict that epigenetic differences induced by composite environmental cues may affect the reproductive success and behaviour of the species clone/s in question. I am also working on a series of interdisciplinary studies on the interface between biology and analytical science with a focus on developing novel means to mitigate pollution and test metabolomic responses of parthenogenetic organisms to environmental stressors. 

Publications

Alfutimie, A., Khudr, MS., Al-Janabi, N., Alkhalaf, F., & Tiddy, G (2019). Palm and olive oils differentially alter phase structure and repulsive interaction between bilayers of gel phase formed by mixed monoglycerides. Colloids And Surfaces A: Physicochemical And Engineering Aspects, 579, 123682. doi: 10.1016/j.colsurfa.2019.123682

Guilbaud, C.*, and Khudr, MS*. (2019). Disturbance and competition drive diversity effects in cabbage-aphid-onion system with intra-specific genetic variation. Cambridge University Press, Bulletin of Entomological Research, 1-13. doi:10.1017/S0007485319000373

Khudr, MS., Purkiss, S. and Hager, R. (2018). Indirect ecological effects interact with community genetic effects in a host–parasite system and dramatically reduce parasite burden. Proceedings of the Royal Society B: Biological Sciences, 285(1886), p.20180891.

Khudr, MS., Purkiss, S., de Sampaio Kalkuhl, A. and Hager, R. (2018). Novel resilience in response to revitalisation after exposure to lethal salinity causes differential reproductive success in an extremely plastic organism. PeerJ, 6, p.e5277.

Khudr, M., Buzhdygan, O., Petermann, J. and Wurst, S. (2017). Fear of predation alters clone-specific performance in phloem-feeding prey. Scientific Reports, 7(1). https://www.nature.com/articles/s41598-017-07723-6.

Khudr M.S., Guilbaud, C. S. E. and Preziosi, R. F. 2017. Host plant and competitor identity matter in genotype × genotype × environment interactions between vetch and pea aphids. Ecol Entomol. doi:10.1111/een.12418

Khudr, M.S., Potter, T., Rowntree, J.K., Preziosi, R.F. 2014. Intraspecific genetic effects versus competition effects in an agro-model pea aphid system. In Moya-Laraño, J., Rowntree, J.K., Woodward, G (Ed.), Advances in Ecological Research. 50:243-266.

Khudr, M. S., Oldekop, J., Shuker, D., R. F. Preziosi. 2013. Parasitoid wasps influence where aphids die via an inter-specific indirect genetic effect. Biology Letters. DOI: 10.1098/rsbl.2012.1151

Zytynska, S. E., Khudr, M. S., Harris, E., and R. F. Preziosi. 2012. Genetic effects of tank-forming bromeliads on the associated invertebrate community in a tropical forest ecosystem. Oecologia, DOI: 10.1007/s00442-012-2310-3

 

 

 

Rebecca WoodsRebecca Woods

icon PhD student

 

Biography

I obtained my BSc in Biomedical Genetics from Newcastle University in 2018, developing an interest in epigenetics and its role in disease development. I have also worked for 14 months as an R&D scientist in the Molecular Biology department at Allergan Biologics Ltd, working in protein and viral-gene therapies, with experience in various molecular analytical techniques. My BBSRC-funded PhD aims to investigate how maternal infection influences offspring neurodevelopment. Maternal immune activation is a risk factor for several neurodevelopmental disorders such as schizophrenia. I plan to focus on possible epigenetic mechanisms which may act as an intervening mechanism by which offspring neurodevelopment is disrupted following maternal infection during pregnancy.

 

 

 

Stephanie CahillStephanie Cahill

icon PhD student

Biography

I completed my undergraduate degree in Psychology and Zoology at the University of Bristol, followed by a Masters in Human Evolution and Behaviour at University College London. My main research interests are in pre and postnatal environment interaction, the effect of parental care on developmental trajectories, stress reactivity, sensitivity to context and the ecological relevance of resilience.

I am part of the BioSocial Centre for Doctoral Training, funded by the BBSRC and ESRC. My PhD project aims to investigate epigenetic mechanisms in the development of resilience, specifically focusing on differential susceptibility. Using longitudinal data genetic, genomic and biosocial environmental data I seek to compare multiple stressors that occur at distinct life stages, focusing on factors that confer resilience using continuous behavioural stress response measures as outcomes of interest. Specifically, I will investigate the mechanisms behind the epigenetic plasticity to stress, while also examining the experience-dependent intergenerational transmission of DNA methylation patterns and behaviour in human and mammalian models.

Publications

Penton-Voak, I. S., Cahill, S., Pound, N., Kempe, V., Schaeffler, S., & Schaeffler, F. (2007). Male facial attractiveness, perceived personality, and child-directed speech. Evolution and human behavior, 28(4), 253-259.

 

Ashbrook DG, Cahill S, Hager R. 2019. A cross-species systems genetics analysis links APBB1IP as a candidate for schizophrenia and prepulse inhibition. Front Behav Neurosci 13:266.

 

 
 

 

 

 

Zhe Yang (Scott) YimZhe Yang (Scott) Yim

icon PhD student

Biography

I graduated from the University of Leicester in 2017 with an undergraduate degree in Biology (Genetics). The aim of my PhD research is to investigate the epigenetic mechanism of plasticity in invertebrate systems and their interactions with the surrounding environment and other organisms. In insects and crustaceans, such as aphids and daphnia, polyphenisms can be induced by environmental conditions, and the same genotype can result in different phenotypes. This multi-disciplinary project combines techniques from different areas such as molecular biology, ecology, evolutionary biology, and epigenetics to determine if epigenetic mechanisms are involved in polyphenisms, and its indirect effects on other organisms.

 

 

 

 

 

Hawa Jahan 

icon PhD student

Biography

I completed my BSc in Zoology in 2012 from the University of Dhaka, Bangladesh followed by a Masters in Genetics and Molecular Biology from the same university. My particular research interest is in evolutionary biology, phenotypic plasticity and molecular epigenetics. My PhD research project, funded by the Commonwealth Scholarship Commission, aims to focus on how environmental change affects the epigenotype in invertebrate systems especially in Aphids and Daphnia. Using different epigenomic and other molecular techniques, this multi-disciplinary project will investigate the effect of changing environmental conditions on life history traits and the underlying epigenetic mechanisms.

 

 

 

 

Jessica Brown 

icon PhD student (co-supervised)

Biography

I graduated from the University of Bath in 2019 with a Bsc in Biology before moving to Manchester to commence my postgraduate research. My interest in neuroscience was sparked by a 12-month undergraduate research placement at Eli Lilly, during which I used organotypic slice cultures to investigate the role of neuroinflammation in the pathology of Alzheimer’s disease. The long-term aim of my MRC-funded PhD in Pharmacology is to develop mGluR5 PAM compounds able to restore cognitive function (and negative symptoms) in patients with schizophrenia. Cognitive impairment associated with schizophrenia (CIAS) represents an unmet clinical need, with no existing pharmacological therapy. Specifically, I plan to evaluate the therapeutic efficacy of mGluR5 PAMs in scPCP and mIA rodent models of schizophrenia through behavioural testing and ex vivo tissue analyses. Using in vitro calcium imaging and ex vivo/in vivo electrophysiologyfacilities provided by collaborative partners at the Universities of Lincoln and Warwick, respectively, Ialso seek to identify the mGluR5-associated neurobiological pathways underlying cognitive deficits. Through elucidating these mechanistic underpinnings, the project ultimately aims to generate a library of mGluR5 PAMs for CIAS which have brain region-/cell-specific signalling profiles and thus fewer adverse side effects.

 

 

 

 

 
 

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.

 

Jarred Lorusso

I obtained my BSc in Psychology with a Professional Placement from Cardiff University in 2019. My placement was based at McLean Hospital in Belmont, MA, focusing on mammalian models of schizophrenia using prepulse inhibition of startle and novel behavioral tasks. My PhD focuses on how maternal infection in pregnancy can interact with a stressful postnatal environment to affect offspring neurodevelopment. Specifically, my project aims to characterize the altered susceptibility (or resilience) of infection-exposed offspring to the long-term behavioral effects of the stress. Beyond immediate behavioural effects, I aim to identify any biological indicators of risk through altered gene or protein expression.

 

 

 

 Alumni (postgraduate research)

  • 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 vice chair of the Portico Library Trust, both based in Manchester.

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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