| In vitro, concentration-dependent,
self-assembly of biological filaments associated
with disease and aging |
In
the premature aging disease Hutchinson-Gilford
progeria syndrome, a stiffening of the nuclear
lamina network, the protein scaffold at the inner
nuclear membrane, is associated with the aberrant
alignment of the protein filaments, known as lamins.
However, it is poorly understood how the properties
of the individual filaments or their concentration
affect the overall material characteristics, such
as stiffness or plasticity, of the nuclear lamina.
A collaborative effort between the Dahl and
the Islam groups examines (a) individual
nanoscale filament stiffness using small angle
X-ray, neutron and light scattering techniques,
(b) filament interactions in solution using standard
biological protein interaction assays, atomic force
microscopy and possibly electron microscopy and
(c) microscopic domains of filament alignment and
network formation as a function of concentration
using polarization light microscopy. The REU student
will use metabolically engineered bacteria to produce
large amount of filament lamin proteins, which
will then be purified. Using multiple solution
phase and optical techniques, the UG student will
determine material properties of the lamin filaments
at multiple length scales. This information will
translate to sub-cellular rheology and ultimately
in developing treatments related to aging and disease. |
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