Biochemical Journal,
Год журнала:
2022,
Номер
479(21), С. 2311 - 2325
Опубликована: Ноя. 11, 2022
In
the
almost
70
years
since
first
hints
of
its
existence,
phosphoinositide,
phosphatidyl-D-myo-inositol
4,5-bisphosphate
has
been
found
to
be
central
in
biological
regulation
plasma
membrane
(PM)
function.
Here,
we
provide
an
overview
signaling,
transport
and
structural
roles
lipid
plays
at
cell
surface
animal
cells.
These
include
being
substrate
for
second
messenger
generation,
direct
modulation
receptors,
control
traffic,
ion
channels
transporters,
cytoskeleton
polarity.
We
conclude
by
re-evaluating
PI(4,5)P2's
designation
as
a
signaling
molecule,
instead
proposing
cofactor
role,
enabling
PM-selective
function
many
proteins.
The
advent
of
clustered
regularly
interspaced
short
palindromic
repeat
(CRISPR)
genome
editing,
coupled
with
advances
in
computing
and
imaging
capabilities,
has
initiated
a
new
era
which
genetic
diseases
individual
disease
susceptibilities
are
both
predictable
actionable.
Likewise,
genes
responsible
for
plant
traits
can
be
identified
altered
quickly,
transforming
the
pace
agricultural
research
breeding.
In
this
Review,
we
discuss
current
state
CRISPR-mediated
manipulation
human
cells,
animals,
plants
along
relevant
successes
challenges
present
roadmap
future
technology.
Chemical Reviews,
Год журнала:
2023,
Номер
123(14), С. 8945 - 8987
Опубликована: Март 7, 2023
Multivalent
proteins
and
nucleic
acids,
collectively
referred
to
as
multivalent
associative
biomacromolecules,
provide
the
driving
forces
for
formation
compositional
regulation
of
biomolecular
condensates.
Here,
we
review
key
concepts
phase
transitions
aqueous
solutions
specifically
that
include
folded
domains
intrinsically
disordered
regions.
The
these
systems
come
under
rubric
coupled
segregative
transitions.
underlying
processes
are
presented,
their
relevance
condensates
is
discussed.
Proceedings of the National Academy of Sciences,
Год журнала:
2022,
Номер
119(28)
Опубликована: Июль 5, 2022
Macromolecular
phase
separation
is
thought
to
be
one
of
the
processes
that
drives
formation
membraneless
biomolecular
condensates
in
cells.
The
dynamics
are
follow
tenets
classical
nucleation
theory,
and,
therefore,
subsaturated
solutions
should
devoid
clusters
with
more
than
a
few
molecules.
We
tested
this
prediction
using
vitro
biophysical
studies
characterize
phase-separating
RNA-binding
proteins
intrinsically
disordered
prion-like
domains
and
domains.
Surprisingly,
direct
contradiction
expectations
from
we
find
characterized
by
presence
heterogeneous
distributions
clusters.
cluster
sizes,
which
dominated
small
species,
shift
continuously
toward
larger
sizes
as
protein
concentrations
increase
approach
saturation
concentration.
As
result,
many
encompass
tens
hundreds
molecules,
while
less
1%
mesoscale
species
several
hundred
nanometers
diameter.
supersaturated
strongly
coupled
via
sequence-encoded
interactions.
also
can
decoupled
solutes
well
specific
sets
mutations.
Our
findings,
concordant
predictions
for
associative
polymers,
implicate
an
interplay
between
networks
sequence-specific
solubility-determining
interactions
that,
respectively,
govern
above
occurs.
Molecular & Cellular Proteomics,
Год журнала:
2021,
Номер
20, С. 100138 - 100138
Опубликована: Янв. 1, 2021
Recent
advances
in
efficiency
and
ease
of
implementation
have
rekindled
interest
ion
mobility
spectrometry,
a
technique
that
separates
gas
phase
ions
by
their
size
shape
can
be
hybridized
with
conventional
LC
MS.
Here,
we
review
the
recent
development
trapped
spectrometry
(TIMS)
coupled
to
TOF
mass
analysis.
In
particular,
parallel
accumulation–serial
fragmentation
(PASEF)
operation
mode
offers
unique
advantages
terms
sequencing
speed
sensitivity.
Its
defining
feature
is
it
synchronizes
release
from
TIMS
device
downstream
selection
precursors
for
quadrupole
configuration.
As
are
compressed
into
narrow
peaks,
number
peptide
fragment
spectra
obtained
data-dependent
or
targeted
analyses
increased
an
order
magnitude
without
compromising
Taking
advantage
correlation
between
mass,
PASEF
principle
also
multiplies
data-independent
acquisition.
This
makes
technology
well
suited
rapid
proteome
profiling,
increasingly
important
attribute
clinical
proteomics,
as
ultrasensitive
measurements
down
single
cells.
The
accuracy
enable
precise
collisional
cross
section
values
at
scale
more
than
million
data
points
neural
networks
capable
predicting
them
based
only
on
sequences.
Peptide
differ
isobaric
sequences
positional
isomers
post-translational
modifications.
additional
information
may
leveraged
real
time
direct
acquisition
postprocessing
increase
confidence
identifications.
These
developments
make
powerful
expandable
platform
proteomics
beyond.
Nature,
Год журнала:
2023,
Номер
613(7943), С. 345 - 354
Опубликована: Янв. 4, 2023
Understanding
how
a
subset
of
expressed
genes
dictates
cellular
phenotype
is
considerable
challenge
owing
to
the
large
numbers
molecules
involved,
their
combinatorics
and
plethora
behaviours
that
they
determine
Nature Methods,
Год журнала:
2022,
Номер
19(8), С. 995 - 1003
Опубликована: Июль 25, 2022
Abstract
Explaining
the
diversity
and
complexity
of
protein
localization
is
essential
to
fully
understand
cellular
architecture.
Here
we
present
cytoself,
a
deep-learning
approach
for
self-supervised
profiling
clustering.
Cytoself
leverages
training
scheme
that
does
not
require
preexisting
knowledge,
categories
or
annotations.
Training
cytoself
on
images
1,311
endogenously
labeled
proteins
from
OpenCell
database
reveals
highly
resolved
atlas
recapitulates
major
scales
organization,
coarse
classes,
such
as
nuclear
cytoplasmic,
subtle
signatures
individual
complexes.
We
quantitatively
validate
cytoself’s
ability
cluster
into
organelles
complexes,
showing
outperforms
previous
approaches.
Moreover,
better
inner
workings
our
model,
dissect
emergent
features
which
clustering
derived,
interpret
them
in
context
fluorescence
images,
analyze
performance
contributions
each
component
approach.
Abstract
Spatial
omics
technologies
enable
a
deeper
understanding
of
cellular
organizations
and
interactions
within
tissue
interest.
These
assays
can
identify
specific
compartments
or
regions
in
with
differential
transcript
protein
abundance,
delineate
their
interactions,
complement
other
methods
defining
phenotypes.
A
variety
spatial
methodologies
are
being
developed
commercialized;
however,
these
techniques
differ
resolution,
multiplexing
capability,
scale/throughput,
coverage.
Here,
we
review
the
current
prospective
landscape
single
cell
to
subcellular
resolution
analysis
tools
provide
comprehensive
picture
for
both
research
clinical
applications.