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Spurlino, J.C., Rodseth, L.E., and Quiocho, 
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carbohydrate complexes. Tryptophan residues in 
the periplasmic maltodextrin receptor for active 
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Quiocho, F.A. 1992. An unlikely sugar substrate 
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MULTIDIMENSIONAL CHROMOSOME STRUCTURE 
JohnW. Sedat, Ph.D., Investigator 
The research of Dr. Sedat and his group is aimed at 
a structural understanding, with functional correla- 
tions, of the interphase chromosomes in the eukary- 
otic nucleus. Three-dimensional structure is ana- 
lyzed at the cellular and subcellular levels. The 
approach involves data collection and computer 
processing at the resolution limits of optical and 
electron microscopy. 
In a complementary collaboration with Dr. David 
Agard (HHMI, University of California, San Fran- 
cisco) and his colleagues, the group seeks answers 
to these questions: How do interphase chromo- 
somes fold in the intact diploid nucleus; and how, 
in detail, does an interphase chromosome change as 
a function of progression through the cell cycle and 
development? What is the defined interphase chro- 
mosome architecture of a specific gene? Is molecu- 
lar information reflected in characteristic structural 
attributes? The groups continue to use Drosophila 
melanogaster for these integrated structural and 
functional studies. 
Nuclear and Chromosomal Structural 
Dynamics: Multidimensional Studies 
Studies of the architecture of chromosomes in- 
clude efforts to understand the role of specific pro- 
teins in chromosomal organization and dynamics. A 
powerful approach is to study structural dynamics 
in the living cell. As a first step, fluorescently la- 
beled proteins or labeled monoclonal antibody Fab 
fragments (MCA-F) are injected into the Drosophila 
embryo, producing, under optimal conditions, little 
or no perturbation of development. 
These laboratories have described in recent years 
the development of multidimensional optical mi- 
croscopy. They now observe routinely the three- 
dimensional distribution of distinct cellular com- 
ponents every 20-30 seconds (five-dimensional 
microscopy: three-dimensional space + time + cel- 
lular component). The time resolution should 
increase ~ 1 0-fold when digital camera and hard- 
ware development are completed in the next few 
months. The laboratories continue to develop a 
computer-based approach to the quantitative ex- 
traction and analysis of large- and small-scale mo- 
tions of chromosomes and other structures within 
the nucleus. 
This methodology has been used to study the in 
vivo distribution and dynamics of topoisomerase II 
(topoll), an enzyme required for chromosome con- 
densation and segregation. Three-dimensional time- 
lapse studies using embryo-injected fluorescently 
labeled topoll (or labeled topoll-specific MCA-F) 
have shown that the concentration of nuclear topoll 
changes dramatically throughout the cell cycles. 
There are at least three pools of topoll. During pro- 
STRUCTURAL BIOLOGY 483 
