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Research Focus
Evolution
Host-parasite interactions
 Parasites sensu lato
Eukaryotic parasites + pathogens + viruses
Ecology
Genetics
High evolutionary dynamics
 Parasites ubiquitous
 Parasites with high evolutionary potential
Large population size
Comparatively shorter generation time
Often haploid genome
Hinrich Schulenburg
AG Evolutionsökologie + Genetik
[Intro]
[Exp Evolution]
Host-Parasite Interactions
Influenza
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
Parasite-Host Interactions
Red Queen Hypothesis
...it takes all the running you can do to keep in the same place...
Influenza Virus
John Tenniel in Through a Looking Glass von Lewis Carroll
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
Parasite-Host Interactions
Red Queen Hypothesis
Very
high
...it takes
all theevolutionary
running you can dodynamics
to keep in the same place...
 extremely high selection pressure
 effect on diversity of traits
Model host Caenorhabditis elegans
Short generation time
Transparent
Cryopreservation
Easy manipulation
Molecular methods
Whole genome sequence
© JJ Ewbank
250µm
Ideal model system
Reproductive biology
 mechanisms of evolution
 genetics  ecology
 selfing hermaphrodite
 rare males
John Tenniel in Through a Looking Glass von Lewis Carroll
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
Artwork from Stuart Kim‘s group
(http://cmgm.stanford.edu/~kimlab/)
[Switch]
[Teaching]
[Intro]
[Exp Evolution]
Signal Cross-Talk + Signal Integration
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
3 Types of Behavioural Defence
G protein chemoreceptors
 physical avoidance
Serotonin signalling
 aversive learning
Insulin-like signalling
 physical avoidance
 reduced feeding
Schulenburg et al. (2008) Immunobiology
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
Schulenburg & Ewbank (2007) Mol Microbiol
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
Model microparasite Bacillus thuringiensis (BT)
Evolution
Soil bacterium
High specificity
Persistent infection
Defence/Virulence evolution
Life-history trade-offs
Genetic + Biodiversity
Co-evolutionary adaptations
S l ti dynamics
Selection
d
i
 spores + BT toxin
accumulate in gut
 germination of spores
 replication + infection
of whole worm
Ecology
C. elegans infected with BT
[Intro]
[Exp Evolution]
[Natural Ecology]
Topics
[Duplication]
[Switch]
[Teaching]
Genetics
Natural variation
Genetic architecture of evolution
Population biology
Genetics of trade-offs
Genotype * environment effects
Evolution by gene duplication
Multiple hosts + parasites
Generation of genetic diversity
Food, microbiota,
predators
Inducible
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication] defence/epigenetics
[Switch]
[Teaching]
Approaches
Evolution
Evolution
Experimental evolution
Phenotypic analysis
(Survival, infection, reproduction,
avoidance + choice behaviours)
Ecology
Genetics
Natural populations
QTL SNP analysis
Phenotypic assays
Genetic analysis (KO, RNAi)
(Survival,infection,reproduction, Population genetics+phylogenies
avoidance + choice behaviours)
Gene expression analysis
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
Ecology
Genetics
Host-Parasite Interactions
Host-Parasite Coevolution
Resistance/
Pathogenicity
Reciprocal
genetic change
Many theoretical models
Interpretation of empirical data often difficult
Life-history
trade-offs
Genetic diversity
Outcrossing
Recombination
Mutation
I
Important
t t problem
bl
in
i natural
t l populations
l ti
Host-Parasite
Interactions
 Multitude of factors affect outcome
underlying genetics
costs of immunity + virulence
multiple parasites + multiple hosts
migration rates
general environmental conditions
Specificity +
Local adaptation
Mechanistic diversity
Pathogenicity mechanisms
Resistance mechanisms
Trade-offs
[Intro]
[Exp Evolution]
Temporal fluctuations
Negative frequency-dependence
Repeated selective sweeps
Overdominant selection
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
[Intro]
[Exp Evolution]
Experimental Evolution
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
Experimental Coevolution
20 replicates
20 replicates
10 replicates
Coevolution
Parasite
Control
Experimental evolution = artificial selection
non-pathogenic BT
 Well known from agriculture
 Observation of evolution in real time
Previous coevolution experiments
 Microbe hosts: Pseudomonas, Paramecium
 Invertebrate hosts: snails, bumble bees, daphnia, flies
Host
Control
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
Non-pathogenic BT
48 host generations
Experimental evolution
Host Coevolution Parasite
Control
Control
Phenotypes
at end
4
8
12
16
36
40
44
48
Genetics
over time
Phenotypic consequences
1 pooled DNA
sample/replicat
e
Reciprocal changes
resistance + pathogenicity
life history trade-offs
Genetics
at end
20 lines/replicate
paired set-up
10 clones/replicate
Life-history trade-off
Genetic changes
Host resistance
Rapid genetic changes across time
Increased genetic diversity
Host population size
Host body size
Parasite pathogenicity
Parasite growth rate
-2
-1
0
1
2
Difference (coevolution - control)
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
Material
Catching the Red Queen…
Average change in alllele frequency
Locus X004
Host microsatellites
9 loci
distributed across genome
Parasite toxin genes
3 genes
specific for original strains
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
0.3
C. elegans All loci
Control
Coevolution
HostCoevolution
control
0.2
0.1
0.0
4
8
12
16
20
24
28
32
36
40
44
48
Host generation
[Intro]
[Exp Evolution]
Fast changes + Genetic diversity
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
Locus-by-Locus Analysis
Genetic differentiation in host
Genetic changes
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
Genetic Changes in B. thuringiensis
Catching the Red Queen...
Average change in gene prevalence
B. thuringiensis toxin genes
Cry genes (toxin)
on plasmids
Bacillus cell
Control
Coevolution
0.5
0.4
0.3
0.2
0.1
0.0
4
Coevolved parasite
Control parasite
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
8
12
16
20
24
28
32
36
40
44
48
Host generations
[Intro]
Gene exchange at the end
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
Current experimental evolution projects
Experimental coevolution
 Coevolution  One-sided adaptation
Genetics of evolution
 Genome sequencing
 SNP mapping + QTL analysis
 Microarray analysis
Evolution of virulence
 Immuno-compromised hosts = entry card
Enhanced parasite adaptation
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
Worms in nature
Evolution
Compost, soil
 mainly Dauer stages
Rotting fruits
 All developmental stages
Ecology
Genetics
Associations with invertebrates
 Isopods
 Millipedes
 Snails
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
Rotting fruits
[Switch]
[Teaching]
Rotting fruits
Chemotaxis
De Bono & Maricq (2005) Annu Rev Neurosci
 Very detailed lab work
 Attractive volatile substances
alcohols, ketones, aldehydes, pyrazines,
ester, aromatic compounds
 So far: no direct connection to ecology!
Kurs Terrestrische Ökologie
[Intro]
[Exp Evolution]
Kurs Terrestrische Ökologie
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
Microbiota
Associated microbes of C. elegans
Associated Microbes
 Extremely widespread
 Important effect  host fitness
 Effect on immune system of host
Microbial diversity
Various Acinetobacter spec.
Bacillus fusiformis
Verschiedene Bacillus spec.
C ll l
Cellulomonas
spec.
Comamonas spec.
Klebsiella terrigena
Pseudomonas monteili
Pseudomonas putida
Pseudomonas spec.
Sphingomonas spec.
Uncultured -proteobacterium
O‘Hara & Shanahan (2006) EMBO Rep
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
Ley et al (2006) Cell
[Switch]
[Teaching]
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
New projects in Kiel
Evolution
Natural habitat of C. elegans
 Where does the worm live when?
Associated microorganisms
 Food microbes  pathogens
 Consideration of bacteria, fungi, protists
Other interactors
Ecology
 Vectors for transport?
 Predators?
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
Genetics
Resistance  Behavioural Defence
Life-history switch
Relationship: Resistance  Behaviour
1.0
-value for natural C. elegans strains
Proportion
survival
Survival rate
per strain
.8
.6
.4
Optimal defence strategy
.2
 general stress response
n
 common
genetic basis: insulin signalling?
0.0
Simone Riß
0.0
.2
.4
.6
.8
1.0
Avoidance rate per strain
[Intro]
[Exp Evolution]
[Natural Ecology]
Ageing in C. elegans
[Duplication]
[Switch]
[Teaching]
Ageing in C. elegans
Cynthia Kenyon
 first paper on ageing in 1993
 mutant animals  double life-span
 responsible gene: insulin receptor DAF-2




[Intro]
Baumeister et al. (2006) J. Endocrinol.
Since then…
downstream of DAF-2  transcription factor DAF-16
several other mechanisms discovered in C. elegans
similar mechanisms in flies + mice + humans
foundation of ageing companies
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
Ageing in C. elegans
Insulin-like Signalling
Apparent principle of longevity
 increased expression of stress response genes
 general stress resistance
Example: Transcription factor
f
DAF-16
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
Baumeister et al. (2006) J. Endocrinol.
 regulation of many stress response genes
[Teaching]
 development
 reproductive rate
[Intro]
[Exp Evolution]
[Natural Ecology]
Insulin-like Signalling
[Duplication]
[Switch]
[Teaching]
Insulin-like Signalling
wildtype N2
daf-2 reducedfunction mutant
daf 2;daf 16
daf-2;daf-16
double mutant
 resistance
 longevity
reproductive rate
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
daf-16 knock-out
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
Insulin Signaling  Immunity
Exposure to pathogenic BT
Insulin signalling  Behavioural defence
Avoidance behaviours
 physical evasion
 reduced feeding
Daniela Tonn
Martin Hasshoff
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
[Intro]
[Exp Evolution]
[Natural Ecology]
Insulin + Defence
Insulin
Signalling
[Duplication]
[Switch]
[Teaching]
Homologies with Humans?
Insulin signalling
First evidence





 role in behavioural defence
 link: physiology  behaviour
G
General
l stress
t
response
 all or nothing
 ideal for r-strategy?
sugar metabolism
ageing
stress resistance
i
immune
system?
t ?
avoidance behaviour?
Main life history switch
 reproduction  defence
 evolution of optimal life-history
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
Philosophy
Evolution
Good science




Teaching
Ecology
Genetics
Background knowledge
Scientific experiment (Basis: Hypothesis)
Diversity of methods
C iti l analysis
Critical
l i + statistics
t ti ti
Enjoyable + interactive environment
 Science is fun!
 Creativity
 Interactive discussion
[Intro]
[Exp Evolution]
[Natural Ecology]
Bachelor Courses
biol105: Bestimmungsübungen + Exkursionen
 Übersicht über Invertebraten
 Übersicht über Tierwelt im Freien
 Experimental design + basic statistics
biol 227 (FSV): Evolution, ecology, genetics
 Specific topics of group work
 Varying focus topics; usually more ecological
biol165: Evolutionsökologie + Genetik
biol 250 (FSV): Ecological immunology +
infection biology
 Einführung in spezielle Themen
Wirt-Parasit Koevolution
Genetik von Abwehrverhalten
[Natural Ecology]
[Duplication]
[Teaching]
biol 226 (FSV): Bio-statistics
 Prinzipien der Evolutionsökologie
[Exp Evolution]
[Switch]
Master Courses
biol106: Ökologie
[Intro]
[Duplication]
 Specific topics of group work
 Varying focus topics; usually more genetic
[Switch]
[Teaching]
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
Master courses
biol263 (LFP) Symbiosis
Last but not least…
Mögliche Prüfungsfragen für biol 101
 Lab practical
 Ecological topics
 C. elegans - microbe interactions
 Warum eignen sich Wirt-Parasit Interaktionen als
Modell zur Untersuchung der Evolution?
 Was besagt die Rote-Königin Hypothese und warum
dient es als Metapher für Wirt-Parasit
Wirt Parasit Koevolution?
 Warum haben "trade-offs" einen wichtigen Einfluss
auf die Evolution?
biol280 (LFP) Ecological genetics + genomics




[Intro]
Lab practical
More genetic topics
Genetics of evolutionary change
Different molecular + analytical techniques
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
[Intro]
[Exp Evolution]
[Natural Ecology]
[Duplication]
[Switch]
[Teaching]
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