Ca^"^, K*, and Cr channels in sea urchin sperm and 
explored their participation in chemotaxis and the 
acrosome reaction. 
Many pathogenic bacteria are capable of exploit- 
ing host cell functions, including signal transduc- 
tion and cytoskeletal rearrangements. These pro- 
cesses are under study in the laboratory of B. Brett 
Finlay, Ph.D. (University of British Columbia, Van- 
couver) . Enteropathogenic Escherichia coli (EPEC) 
adhere to epithelial cells and cause a rearrangement 
of several cytoskeletal proteins. This adherence 
leads to disruption of transepithelial permeability. 
It also triggers host cell tyrosine kinase activity, re- 
sulting in tyrosine phosphorylation of a 90-kDa host 
cytoskeletal protein. Other invasive pathogens such 
as Yersinia and Listeria species also utilize host ty- 
rosine kinases to mediate bacterial uptake into epi- 
thelial cells. Pirating of these functions appears to 
participate in disease production. 
Initiation by human RNA polymerase II at the pro- 
moters of protein-coding genes requires several gen- 
eral factors. Interactions among these factors were 
characterized by Jack F. Greenblatt, Ph.D. (Univer- 
sity of Toronto) and his colleagues, and factor re- 
quirements for recognition of a promoter were de- 
fined. The general factor TBP was found to be a 
target for several activator proteins: herpesvirus 
VP16, the human anti-oncogenic protein p53, and 
the human activator Spl. Antitermination by the 
phage X N protein in bacteria was used as a model 
system to study control of transcription termination. 
This system was reconstituted in vitro with seven 
pure proteins, and detailed mechanistic models for 
antitermination were developed. 
The research of Sergio Grinstein, Ph.D. (Univer- 
sity of Toronto) and his colleagues aims at under- 
standing the mechanisms that regulate intracellular 
pH. Three separate systems were investigated: 1) 
Na^/H^ antiport was studied using phosphatase in- 
hibitors. These agents phosphorylated the antiport 
and stimulated its exchange activity, suggesting that 
direct phosphorylation maybe an important control- 
ling mechanism. 2) A regulated H"^ conductance was 
also identified. Stimulated leukocytes depolarize 
and undergo a burst of metabolic acid generation. A 
sizable fraction of this acid is extruded via a pH-, 
voltage-, and kinase-sensitive conductance. 3) Pro- 
ton pumps contribute to cytosolic pH regulation 
and to the establishment and maintenance of the 
acidic interior of phagosomes. Studies of ionic per- 
meability indicated that the intrinsic pH sensitivity 
of vacuolar-type pumps is the main determinant of 
intraphagosomal pH. 
P-glycoprotein (P-gp) is a membrane-bound drug 
efflux pump encoded by the mdr gene family. 
which is responsible for the onset of multidrug resis- 
tance (MDR) in tumor cells. The structure/function 
analysis of P-gp has been initiated by the laboratory 
of Philippe Gros, Ph.D. (McGill University, Mon- 
treal) in chimeric and mutant proteins, using full- 
length cDNA clones corresponding to the three 
members of the mdr gene family, and has shown 
that the membrane-associated domains are key struc- 
tural determinants for substrate recognition. A new 
series of simple lipophilic cations has been identi- 
fied as model substrates for P-gp. Functional com- 
plementation of the yeast mdr homologue STE6 has 
been carried out successfully. 
Bacterial mutants of the gene for peptidyl-tRNA 
hydrolase prevent phage X vegetative growth. Wild- 
type and mutant alleles of the pth gene were cloned 
and sequenced by Gabriel Guarneros-Pena, Ph.D. 
(National Polytechnic Institute, Mexico City) and 
his colleagues, and the wild-type Pth protein was 
isolated and purified. Sequence analysis of two dis- 
tinct phage mutations, termed bar, which overcome 
the host-cell Pth defect, revealed a nearly identical 
l6-bp DNA segment. Transcription through the 
wild-type bar region is required for X exclusion, but 
in a plasmid vector, arrests protein synthesis and 
kills Pth-defective cells. A unifying model is pro- 
posed in which Bar RNA and Pth participate in termi- 
nation of protein synthesis. 
The laboratory of Luis R. Herrera-Estrella, Ph.D. 
(National Polytechnic Institute, Irapuato) is inter- 
ested in the study of the molecular events that regu- 
late carbon assimilation in plants. To understand 
these events, some of the DNA sequences and pro- 
tein factors that mediate the tissue-specific and 
light-inducible expression of genes involved in pho- 
tosynthesis have been identified. The role of molec- 
ular chaperones that have been implicated in the 
assembly of ribulose bisphosphate carboxylase have 
been studied using transgenic plants harboring anti- 
sense gene constructs for these molecular chaper- 
one genes. The maize and rice genes encoding one 
of the key enzymes in carbon assimilation, the su- 
crose phosphate synthase, has been isolated. 
One strategy that has been very effective in identi- 
fying mammalian genes required for pattern forma- 
tion has been to use cross-species sequence conser- 
vation to clone related genes from vertebrates and 
invertebrates. A number of families of mammalian 
genes have been identified in this manner, based on 
their homology to Drosophila genes that control 
the process of segmentation. These families include 
the Wnt genes that are homologues of the Drosoph- 
ila wingless ( wg) gene, the En genes that are simi- 
lar in structure to the Drosophila engrailed (en) 
gene, the Pax genes that contain a conserved paired 
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