Developmental & Comparative Immunology,
Journal Year:
2024,
Volume and Issue:
161, P. 105258 - 105258
Published: Aug. 29, 2024
What
are
the
future
directions
of
fields
developmental
and
comparative
immunology?
In
thinking
through
this
question
as
I
write,
find
myself
marvelling
at
very
long
ways
that
we
have
come
since
began
a
PhD
student
some
50
years
ago.
think
cannot
know
what
technical
theoretical
advances
will
emerge
in
future,
nor
our
initial
aims
survive
realities
appears
sights,
often
from
unexpected
directions.
feel
should
not
allow
already
about
well-studied
systems
to
blind
us
wide
range
possibilities,
remaining
humble
seeker
helps
uptake
new
realities.
Finally,
it
would
be
good
try
answering
whole
questions
immunology,
how
why.
Science Advances,
Journal Year:
2025,
Volume and Issue:
11(17)
Published: April 23, 2025
In
its
natural
habitat,
Caenorhabditis
elegans
must
distinguish
friend
from
foe.
Pseudomonas
are
abundant
in
the
worm’s
environment
and
can
be
nutritious
or
pathogenic.
Previously,
we
found
that
worms
learn
to
avoid
aeruginosa
vranovensis
through
a
small
RNA
(sRNA)–mediated
pathway
targeting
C.
gene
maco-1
,
this
behavior
is
inherited
for
four
generations.
Here,
show
learns
transgenerationally
another
pathogenic
bacteria
fluorescens
15
(PF15).
The
PF15
sRNA,
Pfs1,
targets
VAB-1
ephrin
receptor
16
nt
of
perfect
match,
suggesting
evolution
distinct
bacterial
sRNA/
target
pair.
Knockdown
both
vab-1
induce
avoidance,
loss
reduces
expression,
placing
genes
sRNA-targeted
avoidance
pathway.
Thus,
multiple
act
as
sRNAs,
expanding
possibilities
trans-kingdom
regulation
behavior.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: June 3, 2024
Abstract
Here
we
report
our
attempt
to
replicate
reports
of
transgenerational
epigenetic
inheritance
in
Caenorhabditis
elegans
.
Published
results
from
multiple
laboratories
show
that
C.
adults
and
their
F1
embryos
exposed
the
pathogen
Pseudomonas
aeruginosa
aversion
behavior
a
exposure-dependent
increase
daf-7/TGFβ
reporter
gene
expression.
However,
one
group
persistence
elevated
daf-7
expression
F2,
F3,
F4
generations.
In
contrast,
failed
consistently
detect
either
avoidance
response
or
beyond
generation.
We
did
confirm
dsRNA
transport
proteins
SID-1
SID-2
are
required
for
intergenerational
(F1)
avoidance,
but
not
Furthermore,
reanalysis
RNA
seq
data
provides
additional
evidence
this
inherited
PA14
may
be
mediated
by
small
RNAs.
The
experimental
methods
well-described,
source
materials
readily
available,
including
samples
reporting
laboratory,
explored
variety
environmental
conditions
likely
account
lab-to-lab
variability.
None
these
adjustments
altered
results.
conclude
example
lacks
robustness,
response,
daf-7p::gfp
progeny,
requires
sid-1
sid-2
,
identify
candidate
siRNAs
target
genes
mediate
response.
eLife,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 1, 2025
C.
elegans’
major
food
source
is
bacteria,
and
worms
are
naturally
attracted
to
many
bacterial
species,
including
pathogenic
Pseudomonas
;
in
fact,
prefer
PA14
as
well
wild
bacteria
over
the
lab
E.
coli
strain
(OP50)
standardly
used
laboratory
setting.
Many
labs
have
shown
that
despite
this
natural
attraction
PA14,
prior
exposure
causes
instead
avoid
PA14.
This
behavioral
switch
can
happen
on
a
relatively
fast
time
scale,
even
within
duration
of
choice
assay.
Here
we
show
accurate
assessment
animals’
true
first
requires
use
paralytic
(azide)
trap
at
their
initial
choice,
prevent
from
avoidance
assay
period.
We
previously
discovered
elegans
25°C
plate-grown
20°C
for
24hrs
not
only
leads
these
animals
switching
but
also
progeny
avoiding
naïve
state,
persists
through
F4
generation.
Other
types
training
cause
P0
and/or
F1
avoidance,
do
induce
transgenerational
(F2
beyond)
inheritance.
showed
(P0-F4)
learned
mediated
by
P11,
small
RNA
produced
P11
both
necessary
sufficient
epigenetic
inheritance
behavior.
highly
expressed
our
standard
growth
conditions
(25°C
surfaces),
other
conditions,
suggesting
reported
failure
observe
F2-F4
most
likely
due
absence
expression
experimenters’
conditions.
Through
mutant
analyses,
tested
genes
–
germline
regulators,
uptake,
interference/processing,
chromatin
modifiers,
neuronal
-
involvement
pathogen
allowing
us
better
understand
molecular
requirements
process.
found
strains
TEI
least
two
P.
vranovensis
fluorescens
15,
avoidance.
The
induced
each
species
functions
specific,
distinct
(Pv1
Pfs1
15
,
respectively)
either
directly
or
indirectly
reduce
levels
gene
maco-1
which
turn
regulates
daf-7
ASI
neuron
subsequent
conservation
multiple
components
mechanism
across
suggests
behavior
be
functional
physiologically
important
Journal of Neurogenetics,
Journal Year:
2025,
Volume and Issue:
unknown, P. 1 - 15
Published: May 1, 2025
Forgetting
behavior
is
a
common
phenomenon
that
has
been
widely
studied
in
various
model
organisms,
including
Caenorhabditis
elegans
(C.
elegans),
Drosophila,
and
mammals
such
as
mice
humans.
Understanding
the
mechanisms
underlying
forgetting
can
provide
valuable
insights
into
potential
treatments
for
memory-related
disorders.
In
this
study,
C.
was
used
organism
to
establish
based
on
PA14
pathogen.
A
proteomic
analysis
of
signaling
pathways
involved
revealed
role
Arp2/3
complex
regulating
pathogen-induced
forgetting.
Manipulation
genes
encoding
components
(arx-1,
arx-2,
arx-3,
arx-5,
arx-7)
led
reduction
duration
Additionally,
one
hour
after
pathogen
removal,
significant
decrease
mRNA
levels
arx-5
arx-7
observed,
along
with
arx-2::mCherry
fluorescence
specific
tissues
elegans.
This
study
demonstrates
exhibits
towards
PA14,
approximately
2
hours.
Pathogen-induced
associated
an
increase
heterogeneous
proteins
localized
cytoskeleton.
Moreover,
expression
related
are
reduced,
inhibiting
cytoskeleton
nucleation
cells.
inhibition
may
contribute
observed
response
PA14.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: June 7, 2024
Abstract
After
examining
the
data
and
methods
presented
in
Gainey,
et
al.,
bioRxiv
,
2024
1
we
conclude
that
authors
did
not
use
an
experimental
paradigm
would
have
allowed
them
to
replicate
our
results
on
transgenerational
epigenetic
inheritance
(TEI)
of
learned
avoidance
regularly
observe
2–5
.
That
is,
agree
with
their
experiments
show
no
evidence
TEI.
However,
there
are
substantial
differences
execution
every
step
work
also
make
it
impossible
for
claim
they
replicating
or
protocols.
Based
these
differences,
do
believe
is
issue
“robustness”
“reliability”
TEI
findings,
but
rather
Hunter
colleagues
fact
tested
central
condition
-
small
RNA
production
by
bacteria
subsequent
uptake
C.
elegans
nor
carried
out
proper
behavioral
imaging
assays
assess
this
behavior.
Our
shows
indeed
example
just
observed
laboratory
settings
PA14,
induced
wild
strains
Pseudomonas
exhibiting
its
robustness.
Just
as
offered
advice
training
colleagues,
happy
advise
anyone
who
wishes
learn
assay.
We
now
performed
absence
azide,
a
deviation
from
protocol
deliberately
made,
found
omission
may
account
most
if
all
results.
It
disingenuous
used
protocol,
given
chose
same
conditions
basic
assay
work,
chemotaxis
assay,
which
been
necessary
order
reproduce
work.
Therefore,
Gainey
al.’s
claims
“irreproducible”
supported
evidence.
Here
we
report
our
attempt
to
replicate
reports
of
transgenerational
epigenetic
inheritance
in
Caenorhabditis
elegans
.
Published
results
from
multiple
laboratories
show
that
C.
adults
and
their
F1
embryos
exposed
the
pathogen
Pseudomonas
aeruginosa
aversion
behavior
a
exposure-dependent
increase
daf-7/TGFβ
reporter
gene
expression.
However,
one
group
persistence
elevated
daf-7
expression
F2,
F3,
F4
generations.
In
contrast,
failed
consistently
detect
either
avoidance
response
or
beyond
generation.
We
did
confirm
dsRNA
transport
proteins
SID-1
SID-2
are
required
for
intergenerational
(F1)
avoidance,
but
not
Furthermore,
reanalysis
RNA
seq
data
provides
additional
evidence
this
inherited
PA14
may
be
mediated
by
small
RNAs.
The
experimental
methods
well-described,
source
materials
readily
available,
including
samples
reporting
laboratory,
explored
variety
environmental
conditions
likely
account
lab-to-lab
variability.
None
these
adjustments
altered
results.
conclude
example
lacks
robustness,
response,
daf-7p::gfp
progeny,
requires
sid-1
sid-2
,
identify
candidate
siRNAs
target
genes
mediate
response.