Professor, Molecular Genetics & Cell Biology,
Dir., Electron Microscopy and Image Processing Lab
B.S., Physical Chemistry, University of Illinois, Urbana, 1959
M.S., Biophysical Chemistry, Hebrew University, Jerusalem, 1962
Ph.D., Biology, Johns Hopkins University, Baltimore, 1966
Sickle Cell Hemoglobin
Sickle cell anemia is caused by the intracellular polymerization
of sickle cell hemoglobin to form rod-like fibers. A knowledge of
the fiber structure could be used for the design of an agent that
could block fiber formation. We have combined the structure of hemoglobin
(known from X-ray crystallography) and the molecular coordinates
of the fiber (determined from electron microscopy) in order to synthesize
a model which shows the intermolecular contacts of the fiber. This
approach has allowed us to determine the contacts which form between
molecules in the fiber. We are now studying how various mutations
(some obtained by site directed mutagenesis) affect fiber structure.
Such studies are expected to account for the structural and chemical
properties of fibers in terms of intermolecular interactions.
Human Erythrocyte Membrane
Red cells are able to elastically deform. The extraordinary importance
of this property can be appreciated from recalling that, although
the human red cell is a biconcave disk eight microns in diameter,
it can easily pass through capillaries half this size. This remarkable
feat is accomplished by the red cell transiently changing its shape
during passage after which its well-known biconcave form spontaneously
and nearly instantly recovers. We are studying the structural basis
of this property using cryo electron microscopy.
The acetylcholine receptor is responsible for transduction of the
nerve impulse to muscular contraction. The receptor lies at the
neuromuscular junction in the muscle membrane. It has five subunits
denoted as a1,a2,b,d,g. Current work in our lab involves labeling
different subunits with monoclonal antibodies against defined defined
sequences in order to determine the subunit arrangement (which appears
to still be a matter of debate in spite of the considerable work
done in other labs). We are using two dimensional crystalline tubes
in order to determine the location of the labels.
M.S. Turner, R.W. Briehl, J.C. Wang, F.A. Ferrone and R. Josephs. (2006). Anisotropy in Sickle Hemoglobin Fibers from Variations in Bending and Twist. J. Mol. Biol. 357 1422 - 1427. (PubMed)
MS Turner, G. Agarwal, C.W. Jones, J.C. Wang, S. Kwong, F.A. Ferrone, R. Josephs and R.W. Briehl. (2006). Fiber Depolymerization. Biophysical Journal. 91 1008 - 1013. (PubMed)
Turner, M. S., Briehl, R. W., Ferrone,
F. A. and Josephs, R. (2003). Twisted protein aggregates and
disease: the stability of sickle hemoglobin fibers. Phys Rev
Lett 90: 128103. (PubMed)
Wang, J. C., Turner, M. S., Agarwal, G., Kwong, S., Josephs, R.,
Ferrone, F. A. and Briehl, R. W. (2002). Micromechanics of
isolated sickle cell hemoglobin fibers: bending moduli and persistence
lengths. J Mol Biol 315: 601-12. (PubMed)
Agarwal, G., Wang, J. C., Kwong,
S., Cohen, S. M., Ferrone, F. A., Josephs, R. and Briehl, R. W.
(2002). Sickle hemoglobin fibers: mechanisms of depolymerization.
J Mol Biol 322: 395-412. (PubMed)
Li, X., Briehl, R. W., Bookchin,
R. M., Josephs, R., Wei, B., Manning, J. M. and Ferrone, F. A. (2002).
Sickle hemoglobin polymer stability probed by triple and quadruple
mutant hybrids. J Biol Chem 277: 13479-87. (PubMed)
Nooney, R., Dhanasekaran, T., Chen,
Y., Josephs, R., Ostafin, A. (2002). Controlling Mesoporous Silicate
Nanoparticle Size with Co-solvent. Chemistry of Materials 14:4721-28
Nooney, R.I., Dhanasekaran, T., Chen,
Y., Josephs, R. and Ostafin, A. (2002). Self-assembled highly ordered
spherical mesoporous silica/gold nanocomposites. A.E. Adv. Mater.