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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 as well as in the bound peptides. These knowledge and
techniques have 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. Students are encouraged to
explore and develop new ways of gaining structural information in
membranes. Over the years, the lab has developed the methods of:
Oriented Circular Dichroism for detecting the orientation
of peptides,
X-ray in-plane Scattering to measure the protein-protein
correlations in
membranes,
Neutron in-plane Scattering to detect and measure
transmembrane pores,
Crystallization of peptide-induced strustures in membranes,
Resolutions of membrane-fusion intermediate and pore
structures,
Analysis of peptide-membrane interactions by GUV
experiments.
We believe that trying new methods is the most interesting part of
research.
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