Introduction 
The human body contains several trilHon (i.e., 
milHon million) cells of a thousand or more dis- 
tinct types. Research in the field of cell biology 
seeks to understand how these various cells are 
constructed and organized, how they differ from 
one another, how they sense and respond to out- 
side influences, how they interact with their 
neighbors to form more complex tissues and or- 
gans, and, in general, how the cells of the body 
are integrated to produce an appropriately func- 
tioning organism. Equally important, research in 
this area is aimed at understanding how these cel- 
lular functions are perturbed by disease. To this 
extent the problems addressed by investigators in 
the Cell Biology and Regulation Program inevita- 
bly impinge on related work in genetics, develop- 
ment, neuroscience, and immunology. For a 
Medical Research Organization it is especially 
gratifying to see how many of the insights gleaned 
from these studies are already beginning to throw 
light on such medically important problems as 
diabetes, heart disease, cancer, muscular dys- 
trophy, cystic fibrosis, and a number of other ge- 
netic disorders. 
The strikingly rapid advances that have oc- 
curred in cell biology in recent years have been 
due, in large part, to earlier progress in biochem- 
istry and cellular physiology, but especially to 
the dramatic developments that have occurred in 
molecular biology since the early 1960s. The 
techniques developed in these fields have been 
invaluable to cell biology, which has always been 
quick to apply different and newly emerging ap- 
proaches to the solution of the many problems of 
cell structure and function. To understand the 
types of research being conducted in contempo- 
rary cell biology, it may be helpful to begin with a 
general account of a "typical" animal cell (Fig- 
ure 1). 
Near the center of each cell is the nucleus, 
which contains the genes (Figure 2) that are 
made of DNA and encode the information neces- 
sary to construct an entire organism and maintain 
its day-to-day activities. The entire complement 
of genes is the genome, which comprises a set of 
instructions encoded in the sequences of the DNA 
molecules (as described more fully in the section 
on genetics). The human genome consists of 46 
chromosomes — 22 pairs of autosomes and 2 sex 
chromosomes. The two copies of each autosome 
are inherited from the mother and the father, re- 
spectively; in females there are two X chromo- 
somes (one from each parent) , while in males the 
Y chromosome is always inherited from the father 
and the X chromosome (Figure 3) is always in- 
herited from the mother. The 46 chromosomes 
comprise a total of about 3 billion pairs of nu- 
cleotides. Estimates vary, but it is thought that 
there may be as many as 100,000 genes in the 
human genome. These genes vary in length from 
around 1,000 to about 2 million nucleotides. 
Each gene encodes the information for a particu- 
lar cellular structure or function. This informa- 
tion, which can be likened to a computer lan- 
guage, is first read (transcribed) into RNA, and 
the message contained within the nucleotide se- 
quence of the RNA molecule is then decoded 
(translated) by the machinery of the cell into a 
different language, or chemical structure. While 
the RNA transcript mirrors exactly the DNA se- 
quence of the gene, the messenger RNA (mRNA) 
that is translated into the amino acid sequence of 
the encoded protein is a highly edited message 
(Figure 4). Generally several intervening (or 
noncoding) sequences called introns are selec- 
tively removed from the transcript. Introns ac- 
count for a considerable proportion of the DNA in 
all higher organisms and, together with several 
other noncoding stretches of DNA (spacer DNA, 
satellite DNA, and other repetitive DNA se- 
quences) , are sometimes referred to as selfish or 
junk DNA. In humans it is estimated that more 
than 90 percent of the DNA in the genome is of 
this kind. The possible functions (if any) of this 
noncoding DNA are not known, but the mecha- 
nisms whereby the coding sequences or exons 
are spliced out and joined together (sometimes in 
different order — a process known as alternative 
splicing) is a subject of considerable interest at 
present. The chemical language of the cell has 20 
different characters or units, known as amino 
acids, which are linked together, again in linear 
arrays, to make proteins. 
Whereas DNA is the blueprint directing the 
cell's development and function, proteins are the 
molecules from which cells are built and which 
carry out most cellular functions. Most genes en- 
code proteins, and each cell contains about 
10,000 different types of protein. That is, each 
cell uses only about 10 percent of the total set of 
genes at any one time. This raises two of the cen- 
tral questions in cell biology today: 1) How are 
genes turned on and off so that each cell type 
expresses only its appropriate set of genes and 
contains only its correct complement of proteins? 
2) How are the genes in a given cell regulated, so 
that the cell can respond appropriately to outside 
influences by changing either the pattern of 
