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Research Interests
Lipid molecules of
cell membranes play
important roles in all sorts of cellular functions, yet their molecular
mechanisms are largely unknown, besides the obvious role of forming a
hydrophobic barrier surrounding aqueous contents. The fact that each
cell maintains its organism-specific lipid compositions and that each
type of lipid has its own distinct physical property strongly suggest
correlations between the physical properties of lipids and lipid
related functions. The challenge to membrane biophysicists is to
show these correlations in the fashion of the standard paradigm, i.e.,
structure-function relationships.
We
found
membran-active
proteins
and
peptides
an
excellent
system for
biophysical studies. Most of these proteins are water-soluble, yet they
spontaneously bind to the lipid matrix of cell membranes and exert
their functions. We started with the simplest antimicrobial
peptides, including gramicidin, alamethicin, melittin, magainin and
protegrin, in order to understand the basic principles of molecular
interactions with membranes. The diversity of these peptides
exposed different aspects of such interactions, and led us to develop
special techniques for investigating the induced structural changes in
membrane. These knowledge and
techniques have also been applied to the studies of amphipathic drugs,
pore-forming proteins, including apoptosis-regulating Bax, and membrane
fusion.
Because
membranes
are
soft
matter,
many
well-established
microscopic
structural
tools have difficulties. Over the years, the lab has
developed many methods for the structural studies of membranes. Below
is our recent structure work: the electron densities of the
barrel-stave pore (left), the toroidal pore (middle), and a pre-stalk
state of membrane fusion.
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