gene-environment interplay: biological embedding of … conference presentations/keynotes... ·...

Gene-Environment Interplay:

Biological Embedding of Experience

University Professor Marla B. Sokolowski, Ph.D., F.R.S.C.Department of Ecology & Evolutionary Biology,

University of Toronto

CIFAR Child & Brain Development Program (CBD)

Co directorsUniversity Professor Marla B. Sokolowski, Ph.D., F.R.S.C.

Weston Senior Fellow of CIFAR, Ecology & Evolutionary Biology, University of Toronto

Professor W. Thomas Boyce, M.D., I.O.M, Pediatrics and Psychiatry,

University of California, San Francisco

How can we think about gene-environment

interplay?

Why are we all different?

Nature or nurture?

Gene-environment interactions prevail

Our genes are listening to our environment (epigenetics)

Biological embedding of early experience has life long effects on our well being

Poor children have

substantially higher

rates of chronic,

disabling diseases,

most of which are

poorly understood.

Some children are more vulnerable than others!

Individual differencesin neural and endocrine responses to stress, brain development and later functioning, Immune system, gut microbiome

Prevention

Developmental Paths: Health Risks Associated with Early Adversity and Low SES

Early Experience

AbuseFamily strifeEmotional neglectHarsh discipline

Health Risks

DepressionDrug abuseAnxietyDiabetesHeart diseaseObesity

Differential susceptibility to the social context

dandelion child

orchid child

Tom Boyce

Brain Development

86 billion neurons

1014 connections

Your brain is sculpted by a

lifetime of experiences,

especially in the first few years

of life and during adolescence.

Brain Development: An engineering marvel

Critical Periods of Development as Windows of Opportunity

0 6 93 2 6 10 14 20 40

months years Age

Higher Cognitive Function

Charles A. Nelson, From Neurons to Neighborhoods, 2000.

Seeing / HearingLanguage

Bra

in P

lasti

cit

y

Research on Critical Period Timing in Child DevelopmentProfs Takao Hensch (Harvard), Janet Werker (UBC), Chuck Nelson (Harvard)

DNA is like books packed in boxesand stacked in a library

CIFAR

Limitless potential to inform and inspire...but they need to be unpacked and read.

CIFAR

Early adversity makes some genes difficult to read. Thoseinvolved in: 1) how we cope with stress, 2) how our braindevelops and works and, 3) how we fight disease.

hard to read

easier to read

epigenetics

Our experience becomes embedded in our genes!

Social interactions and inheritance of parenting style. Natural Variations in Mothering in the Rat: High and Low Lickers and Groomers.

CBD Researcher Prof Michael Meaney (McGill, Singapore)

Low licking and grooming High licking and grooming

Cross fostering

Meaney Lab

Associations between Epigenetics and Early Life Trauma

Famine (Heijmans et al., 2008)

Rwandan genocide(Vukojevic et al., 2014)

Holocaust (Yehuda et al.,2014)Transgenerational

effects

Child abuse/neglect (Suderman et al., 2014, Mehta et al., 2013

Klengel et al., 2013, McGowan et al. 2009)

Epigenetic Changes

Epigenetics and Early Life Experience: Meaney, Kobor, Sokolowski, Kolb, Boyce, Szyf, Hertzman, Suomi, Hensch, Werker, Binder, Robinson,

Sokolowski Lab

Molecular mechanisms:How does gene-environment interplay actually work?

Funding for my research

SOKOLOWSKI LAB

DNA methylation

Histone modifications (G9a)

development

Behavioural epigenetics?

Epigenetic factors can regulate gene expression

Sokolowski Lab: Ina Anreiter

Anreiter, Kramer, Sokolowski (2017) Proc. Natl. Acad. Science

Genetic predisposition (DNA sequence variation) affects whether a gene is epigenetically modified

Adult Fly Foraging Arena

Anreiter, Kramer, Sokolowski 2017 Proc. Nat.l Acad. Science

Rover sitter

The foraging gene and its rover and sitter genetic variants

The foraging gene encodes an enzyme called PKGfound in the brain of flies and other organisms including humans.

Rover

Anreiter, Kramer, Sokolowski 2017 Proc. Nat.l Acad. Science

www.chickencrap.com

Cost of Exploration

Behaviour: G9a regulates the rover-sitter difference in adult foraging

Anreiter, Kramer, Sokolowski (2017) Proc. Natl. Acad. Science

foraging has four methylated promoters

Anreiter, Kramer, Sokolowski (2017) Proc. Natl. Acad. Science

pr4: methylation RNA expression Rover more less Sitter less more

EHMT mediates rover-sitter differences in methylation, expression, and behaviour

0

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Promoter 4 (pr4:) G9a mediates Rover-sitter differences in methylation and expression

Anreiter, Kramer, Sokolowski (2017) Proc. Natl. Acad. Science

Anreiter, Kramer, Sokolowski (2017) Proc. Nalt. Acad. Science

A candidate foraging gene genetic variant for the rover/sitter differences in adult

foraging behaviour that is epigenetically regulated by G9a.

Anreiter, Kramer, Sokolowski (2017) Proc. Nalt. Acad. Science

Epigenetics by DNA variant interactions.

Are they common?

Are the epigenetic marks reversible.

Are they inherited through the generations?

Early adversity sets developmental trajectories for health, learning and behaviour across the life-time.

How: mechanisms?

When: sensitive periods?

What: early adversities?

(individual differences, societal outcomes)

Child development is a critical foundation for community and economic development, and positive development is built from positive relationships. Capable children become the foundation of a prosperous and sustainable society.

Thank you!