Jan-Feb 2014 ASCB Newsletter - page 6-7

Protein sorting at a synthetic membrane-
membrane interface. A GUV-GUV interface
formed by the small adhesive protein
(green) excludes large proteins (red) via
a purely passive mechanism. Photo: Eva
Schmid, Matt Bakalar
Science Highlights, continued from p.1
Biophysical Approaches to
Understanding the Cell
Kicking off the biophysics
thread was the Saturday
special interest subgroup
called Building the Cell.
Among the presenters
was bioengineer Dan
Fletcher of the University
of California, Berkeley,
who described new
work on reconstituting
cell membranes. When
starting the project,
Fletcher said, he wanted
to know how the size of
a molecule influences
its ability to segregate at
membrane interfaces.
To answer the
question, Fletcher together with Eva Schmid,
Matt Bakalar, and colleagues made a model of
membrane interfaces with giant unilamellar
vesicles and various synthetic proteins of
different sizes. They found that exclusion of
proteins at interfaces is size dependent and
does not require active help from the cell.
This exclusion is important for cell processes
like T-cell activation, Fletcher believes, where
adhesion molecules with large extracellular
domains are excluded from regions where
ligand-receptor pairs interact.
Later on Saturday at the Molecular Sensors
and Actuators special interest subgroup,
Mathieu Coppey of the Institut Curie in Paris
explained how his lab deployed “nanomagnets,”
super-paramagnetic nanoparticles coated with
signaling proteins, to study localized signaling
within cells. Once nanomagnets have been
introduced into cells, the researchers then use a
larger magnet outside the cell to localize them
to specific subcellular locations and observe the
The coated nanomagnets were able to
function as signaling platforms, with effects
specific to the location of the magnet. For
example, one protein that the researchers
attached to the nanomagnets (GEF TIAM1)
was able to activate downstream proteins at the
plasma membrane. However, when they brought
that same protein-coated nanomagnet to the
leading edge of a migrating cell, it promoted
signaling that led to the formation of actin
scaffolds near the magnet. Coppey said that the
work demonstrated that signal transduction
is really compartmentalized in the cell. “We
expected that the signal would
spread but everything that we
activated stayed local… that was
a big surprise.”
P-granules were the focus
Monday at the Physical Biology
of the Cell Symposium, where
Frank Jülicher, director of the
Max Plank Institute for the
Physics of Complex Systems
in Dresden, spoke about
the organization of the cell
cytoplasm by phase separation.
P-granules are non-membrane-
bound assemblies of proteins
and RNA in lipid drops that
Jülicher compared to vinegar in
an oil emulsion. Because they act
like an emulsion, the granules
undergo Ostwald ripening: The contents of
smaller lipid drops dissolve and are redeposited
in more energetically stable larger drops.
At the “Emerging Technologies” workshop
on Tuesday, Feng Zhang described genome
editing with CRISPR gene-snipping enzymes
derived from the yogurt bacterium
. CRISPR is an anti-phage defense
used by the bacterium. Since 2011, Zhang’s
lab has worked to modify CRISPR for genome
editing. They were able to optimize CRISPR
design, and now researchers can access all of
Zhang’s CRISPR reagents at Addgene.
Cell Biological Approaches to
Understanding Disease
The medicine thread for Sunday included
the Frontier Symposium in Cell Biology and
Medicine, at which Huda Zoghbi of the Baylor
College of Medicine presented her pioneering
research on Spinocerebellar Ataxia 1 (SCA1),
a progressive brainstem and ataxia dysfunction
that her lab has been studying since 1993.
More recently, her lab demonstrated that
SCA1 pathogenesis is caused by a gain-of-
function mechanism in the protein ataxin-1
and that reducing ataxin-1 slows the disease
pathology. Zoghbi’s findings indicated that
phosphorylation at position S776 is a potential
therapeutic target.
In following up, Zoghbi described how her
lab was able to demonstrate that the quantity
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Science Highlights, continued on p. 9
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