Monalisa Manurung

08-114

OVERVIEW OF MOLECULAR CELL BIOLOGY

The beginning of modern medicine can be traced back to centuries

ago when physicians and scientists began studying human anatomy from
cadavers in morgues and animal physiology following
hunting expeditions. Gradually, from the study of animals
and plants in greater detail and the discovery of microbes,
scientific principles governing life lead to the emergence of
the biological sciences.

As biological science developed and expanded, scientists and

physicians began to utilize the principles of biological sciences
to solve challenges of human diseases
while continuing to explore the fundamentals of life in greater
detail. With ever-evolving state-of-the-art scientific tools, our
understanding of how cells, tissues, organs, and entire
organisms function, down to the level of molecular and
subatomic structure, has resulted in modern biology with an
enormous impact on modern healthcare and the discovery of
amazing treatments for disease at an exponential pace

Significant progress has been made in molecular

studies of organ development, cell signaling, and
gene regulation. The advent of recombinant DNA
technology, polymerase chain reaction (PCR)
techniques, and next-generation genomic
sequencing, which resulted in the sequencing of
the human genome, holds the potential to have a
transformational influence on healthcare and
society this century by not only broadening our
understanding of the pathophysiology of disease,
but also by bringing about necessary changes in
personalized medicine

Todays practicing surgeons are becoming

increasingly aware that many modern surgical
procedures rely on the information gained through
molecular research (i.e., personalized surgery).
Genomic information, such as deleterious BRCA and
RET proto-oncogene mutations, is being used to help
direct prophylactic procedures to remove potentially
harmful tissues before they do damage to patients.
Molecular engineering has led to cancer-specific gene
therapy that could serve in the near future as a more
effective adjunct to surgical debulking of tumors than
radiation or chemotherapy,

 so surgeons will benefit from a clear

introduction to how basic
biochemical and biological
principles relate to the developing
area of molecular biology.
This chapter reviews the current
information on modern
molecular biology for the surgical
community.

Basic Concepts of Molecular Research

The modern era of molecular biology, which has been mainly concerned
with how genes govern cell activity, began in 1953 when James D. Watson
and Francis H. C. Crick made one of the greatest scientific discoveries by
deducing the double helical

1 structure of deoxyribonucleic acid (DNA).1,2 The year

2003 marked the 50th anniversary of this great discovery. In the same year,
the Human Genome Project completed with sequencing approximately
20,000 to 25,000 genes and 3 billion

2 base pairs in human DNA.3 Before 1953, one of the

most
mysterious aspects of biology was how genetic material was precisely
duplicated from one generation to the next. Although DNA had been
implicated as genetic material, it was the base-paired structure of DNA
that provided a logical interpretation of how a double helix could unzip
to make copies of itself. This DNA synthesis, termed replication,
immediately gave rise to the notion that a template was involved in the
transfer of information between generations, and thus confirmed the
suspicion that DNA carried an organisms hereditary information.

Within cells, DNA is packed tightly into chromosomes. One

important feature of DNA as genetic material is its ability to
encode important information for all of a cells functions (Fig.
15-1). Based on the principles of base complementarity,
scientists also discovered how information in DNA is
accurately transferred into the protein structure. DNA serves
as a template for RNA synthesis, termed transcription,
including messenger RNA (mRNA, or the protein-encoding
RNA), ribosomal RNA (rRNA), and transfer RNA (tRNA). mRNA
carries the information from DNA to make proteins, termed
translation, with the assistance of rRNA and tRNA. Each of
these steps is precisely controlled in such a way that genes
are properly expressed in each cell at a specific time and
location. In recent years,

New classes of noncoding RNAs (ncRNA), for example,

microRNA (or miRNA), Piwi-interacting RNA (or piRNA),
and long intergenic noncoding RNA (or lincRNA), have
been identified. Although the number of ncRNAs
encoded in the human genome is unknown and a lot of
ncRNAs have not been validated for their functions,
ncRNAs have been associated to regulate gene
expression through posttranscriptional gene regulation
such as mRNA degradation or epigenetic regulation
such as chromatin structure modification and DNA
methylation induction.4 Consequently, the differential
gene activity in a cell determines its actions,
properties, and functions.

Molecular Approaches to Surgical

Research
Rapid advances in molecular and cellular biology
over the past half century have revolutionized the
understanding of disease and will radically
transform the practice of surgery. In the future,
molecular techniques will be increasingly applied
to surgical disease and will lead to new strategies
for the selection and implementation of operative
therapy. Surgeons should be familiar with the
fundamental principles of molecular and cellular
biology so that emerging scientific breakthroughs
can be translated into improved care of the
surgical patient

Figure 15-1. The flow of genetic information from DNA to

protein
to cell functions. The process of transmission of genetic information
from DNA to RNA is called transcription, and the process of
transmission from RNA to protein is called translation. Proteins are
the essential controlling components for cell structure, cell signaling,
and metabolism. Genomics and proteomics are the study of the
genetic composition of a living organism at the DNA and protein
level, respectively. The study of the relationship between genes and
their cellular functions is called functional genomics.

The greatest advances in the field of molecular biology have

been in the areas of analysis and manipulation of DNA.1
Since Watson and Cricks discovery of DNA structure, an
intensive effort has been made to unlock the deepest
biologic secrets of DNA. Among the avalanche of technical
advances, one discovery in particular has drastically
changed the world of molecular biology: the uncovering of
the enzymatic and microbiologic techniques that produce
recombinant DNA. Recombinant DNA technology involves
the enzymatic manipulation of DNA and, subsequently, the
cloning of DNA. DNA molecules are cloned for a variety of
purposes including safeguarding DNA samples, facilitating
sequencing, generating probes, and expressing
recombinant proteins in one or more host organisms.

DNA can be produced by a number of means, including

restricted digestion of an existing vector, PCR, and cDNA
synthesis. As DNA cloning techniques have developed over
the last quarter century, researchers have moved from
studying DNA to studying the functions of proteins, and
from cell and animal models to molecular therapies in
humans. Expression of recombinant proteins provides a
method for analyzing gene regulation, structure, and
function. In recent years, the uses for recombinant proteins
have expanded to include a variety of new applications,
including gene therapy and biopharmaceuticals. The basic
molecular approaches for modern surgical research include
DNA cloning, cell manipulation, disease modeling in
animals, and clinical trials in human patients.