Introduction to
Molecular Biology and Genomics
Molecular Biology
... is the study of biology at a molecular level.
The field overlaps with other areas of biology, particularly genetics and
biochemistry
Molecular biology concerns itself with understanding the interactions between the
various systems of a cell, including the interrelationship of DNA, RNA and protein
synthesis and learning how these interactions are regulated.
Biochemistry and Genetics
Biochemistry is the study of molecules (e.g. proteins). Biochemists take an
organism or cell and dissect it into its molecular components, such as enzymes,
lipids and DNA, and reconstitute them in test tubes (in vitro).
Genetics is the study of the effect of genetic differences on organisms. Often this
can be inferred by the absence of a normal component (e.g. one gene).
Overview
Overview of the cell
Different sizes/functions
Organised structure
genetics
How Molecular Biology came about?
Microscopic biology began in 1665
Robert Hooke (1635-1703) discovered organisms are made up of cells
Matthias Schleiden and Theodor Schwann , recognized the similarities between
plant and animal cells & further expanded the study of cells in 1830s
Major events in the history of Molecular Biology 1800 - 1870
1865 Gregor Mendel discovers the basic rules of heredity of garden pea.
An individual organism has two alternative heredity units for a given trait
(dominant trait v.s. recessive trait)
1869 Johann Friedrich Miescher discovered DNA and named it nuclein.
1899 Richard Altmann renamed nuclein to nucleic acid.
By 1900, chemical structures of all 20 amino acids had been identified
1953 biochemist James Watson & Francis Crick deduced the double helical
structure of DNA
discovered the structure of DNA ushered in the era (turning point) of
molecular biology .
1997 E. Coli sequenced
1999 First human chromosome (number 22) sequenced
April 2003 Mouse genome is sequenced.
April 2004 Rat genome sequenced.
DNA
Contained in the nucleus
Arranged in 22 chromosomes, plus two sex chromosomes
Two copies of each
Around 2m DNA
Therefore, very tightly packed
DNA function
Carries the blueprint for life
Duplication for new cells
Make proteins for biological functions:
What is Life made of?
What is a cell
structural and functional units of all living organisms
A cell is the smallest unit that is capable of performing life functions
unicellular and multicellular organisms
bacteria vs. human
Characteristics of Cells and Life
All living things (single and multicellular) are made of cells that share some
common characteristics:
basic shape – spherical, cubical, cylindrical
internal content – cytoplasm, surrounded by a membrane
DNA chromosome(s), ribosomes, metabolic capabilities
Two basic cell types: eucaryotic and procaryotic
Characteristics of Life
Growth and development
Reproduction and heredity – genome composed of DNA packed in chromosomes;
produce offspring sexually or asexually
Metabolism – chemical and physical life processes
Movement and/or irritability – respond to internal/external stimuli; self-propulsion
of many organisms
Cell support, protection, and storage mechanisms – cell walls, vacuoles, granules
Transport of nutrients and waste
Characteristics of Cells
Eucaryotic cells
Procaryotic cells
Cell biology is a scientific discipline that studies cells – their
physiological properties, their structure, the organelles they contain, interactions
with their environment, their life cycle, division and death. This is done both on a
microscopic and molecular level.
Cell (in biology), is the basic unit of life. Cells are the smallest structures capable
of basic life processes, such as taking in nutrients, expelling waste, and
reproducing. All organisms, such as bacteria and protozoa, are unicellular or
single-celled organism, meaning they consist of a single cell. Plants, animals, and
fungi are multicellular, that is, they are composed of a great many cells working in
concert.
Eukaryotic cells are typically about ten times larger than prokaryotic cells. In
animal cells, the plasma membrane forms the cell’s outer boundary. With a design
similar to the plasma membrane, a cell wall, of prokaryotic cells, it separates the
cell from its surroundings and regulates the traffic across the membrane.
The eukaryotic cell cytoplasm is similar to that of the prokaryote cell except for
one major difference: Eukaryotic cells house a nucleus and numerous other
membrane-enclosed organelles. Like separate rooms of a house, these organelles
enable specialized functions to be carried out efficiently. The building of proteins
and lipids, for example, takes place in separate organelles where specialized
enzymes geared for each job are located.
Schematic of typical animal cell, showing subcellular components. Organelles: (1)
nucleolus (2) nucleus (3) ribosome (4) vesicle (5) rough endoplasmic reticulum
(ER) (6) Golgi apparatus (7) Cytoskeleton (8) smooth ER (9) mitochondria (10)
vacuole (11) cytoplasm (12) lysosome (13) centrioles .
The nucleus was the first organelle to be discovered. The probably oldest
preserved drawing dates back to the early microscopist Antonie van Leeuwenhoek
(1632 – 1723). He observed a "Lumen", the nucleus, in the red blood cells of
salmon . It is the largest cellular organelle in animals. In mammalian cells, the
average diameter of the nucleus is approximately 6 micrometers (μm), which
occupies about 10% of the total cell volume.The viscous liquid within it is called
nucleoplasm, and is similar in composition to the cytosol found outside the
nucleus.It appears as a dense, roughly spherical organelle.
In cell biology, the nucleus referred to as the "control center", is a membraneenclosed organelle found in eukaryotic cells .The cell nucleus contains the majority
of the cell's genetic material, in the form of multiple linear DNA molecules
organized into structures called chromosomes. The main function of the cell
nucleus is to control gene expression and mediate the replication of DNA during
the cell cycle, therefore it is the control center of the cell.
Nuclear envelope and pores
The main structures making up the nucleus are the nuclear envelope, The nuclear
envelope otherwise known as nuclear membrane consists of two cellular
membranes, an inner and an outer membrane, arranged parallel to one another
and separated by 10 to 50 nanometers (nm).It encloses the entire organelle and
separates its contents from the cellular cytoplasm , serving as a barrier to prevent
macromolecules from diffusing freely between the nucleoplasm and the cytoplasm.
The outer nuclear membrane is continuous with the membrane of the rough
endoplasmic reticulum (RER), and is similarly studded with ribosomes. The space
between the membranes is called the perinuclear space and is continuous with the
RER lumen.
The eukaryotic cell nucleus. Visible in this
diagram are the ribosome-studded double
membranes of the nuclear envelope, the DNA
(complexed as chromatin), and the nucleolus.
Within the cell nucleus is a viscous liquid called
nucleoplasm, similar to the cytoplasm found
outside the nucleus.
A cross section of a nuclear pore on the
surface of the nuclear envelope (1). Other
diagram labels show (2) the outer ring,
(3) spokes, (4) basket, and (5) filaments.
Nuclear pores, which provide aqueous channels through the envelope, are
composed of multiple proteins, collectively referred to as nucleoporins.The pores
are 100 nm in total diameter; however, the gap through which molecules freely
diffuse is only about 9 nm wide, due to the presence of regulatory systems within
the center of the pore. This size allows the free passage of small water-soluble
molecules while preventing larger molecules, such as nucleic acids and larger
proteins, from inappropriately entering or exiting the nucleus. The movement of
larger molecules such as proteins is carefully controlled, and requires active
transport regulated by carrier proteins. Nuclear transport is crucial to cell function,
as movement through the pores is required for both gene expression and
chromosomal maintenance.
The nucleus of a typical mammalian cell will have about 3000 to 4000 pores
throughout its envelope, each of which contains a donut-shaped, eightfoldsymmetric ring-shaped structure at a position where the inner and outer
membranes fuse. Attached to the ring is a structure called the nuclear basket that
extends into the nucleoplasm, and a series of filamentous extensions that reach
into the cytoplasm. Both structures serve to mediate binding to nuclear transport
proteins.
Nuclear transport