gene-environment interplay: biological embedding of … conference presentations/keynotes... ·...
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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
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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
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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
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Poor children have
substantially higher
rates of chronic,
disabling diseases,
most of which are
poorly understood.
Some children are more vulnerable than others!
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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
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Differential susceptibility to the social context
dandelion child
orchid child
Tom Boyce
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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
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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
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Research on Critical Period Timing in Child DevelopmentProfs Takao Hensch (Harvard), Janet Werker (UBC), Chuck Nelson (Harvard)
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DNA is like books packed in boxesand stacked in a library
CIFAR
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Limitless potential to inform and inspire...but they need to be unpacked and read.
CIFAR
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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!
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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)
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Low licking and grooming High licking and grooming
Cross fostering
Meaney Lab
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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,
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Sokolowski Lab
Molecular mechanisms:How does gene-environment interplay actually work?
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Funding for my research
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SOKOLOWSKI LAB
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DNA methylation
Histone modifications (G9a)
development
Behavioural epigenetics?
Epigenetic factors can regulate gene expression
Sokolowski Lab: Ina Anreiter
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Anreiter, Kramer, Sokolowski (2017) Proc. Natl. Acad. Science
Genetic predisposition (DNA sequence variation) affects whether a gene is epigenetically modified
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Adult Fly Foraging Arena
Anreiter, Kramer, Sokolowski 2017 Proc. Nat.l Acad. Science
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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
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www.chickencrap.com
Cost of Exploration
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Behaviour: G9a regulates the rover-sitter difference in adult foraging
Anreiter, Kramer, Sokolowski (2017) Proc. Natl. Acad. Science
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foraging has four methylated promoters
Anreiter, Kramer, Sokolowski (2017) Proc. Natl. Acad. Science
pr4: methylation RNA expression Rover more less Sitter less more
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EHMT mediates rover-sitter differences in methylation, expression, and behaviour
0
20
40
60
80
100
120
140
160
Rela
tiv
e E
xp
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ion
(%
)
for pr4 expression
***
0
5
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20
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% i
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for pr4 methylation
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Promoter 4 (pr4:) G9a mediates Rover-sitter differences in methylation and expression
Anreiter, Kramer, Sokolowski (2017) Proc. Natl. Acad. Science
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Anreiter, Kramer, Sokolowski (2017) Proc. Nalt. Acad. Science
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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
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Epigenetics by DNA variant interactions.
Are they common?
Are the epigenetic marks reversible.
Are they inherited through the generations?
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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)
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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.
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Thank you!