The biosynthesis and function of membrane lipids
have been the subject of intense research in the last
twenty years because of their important roles in signal
transduction and membrane assembly. Our laboratory
has devised general autoradiographic screens for detecting
bacterial or animal cell mutants defective in specific
enzymes of lipid synthesis. We have discovered over
20 genes in E. coli and other Gram-negative bacteria
that are required for membrane lipid assembly. Our
most intriguing discovery has been the recognition
of a new family of glucosamine-based lipids in E.
coli. These substances are precursors of endotoxin
(lipid A), which makes up the outer surface of E.
coli. Endotoxins also play an important role in the
pathogenesis of gram-negative infections. We are especially
interested in the mechanism and extraordinary potency
of endotoxins as activators of cytokine synthesis
in macrophages. We have elucidated the key enzymatic
steps of endotoxin biosynthesis and modification,
and are now exploring the molecular biology of the
endotoxin system in diverse bacteria with sequenced
genomes. The endotoxin pathway is an excellent target
for the development of new antibiotics.
A entirely new project is has been initiated to isolate
and identify all minor unknown lipids of animal cells
("structural lipidomics"), which is funded
by a new NIGMS Glue Grant called LIPID MAPS. This
grant provides the laboratory with a state of the
art mass spectrometry facility, and several individuals
to manage it and train new people.
Students participate in all aspects of the research
program. Weekly lab meetings and seminars are interactive,
and explore new directions for each of the projects.
The laboratory currently consists of 14 individuals,
including 5 graduate students, seven postdoctoral
fellows, one undergraduate, and one senior staff person
in the area of mass spectrometry.
