Transcript for Video "A Window into Life"
Category: Non-Interactive Media
Authors: Kenneth Eward, Travis Vermilye
Synopsis: This short-length animated video features highlights from a 2007 suite of six science animations produced for the Cincinnati Children's Hospital Medical Center. Topics from this suite, which include molecular biological themes, cell signaling and organogenesis have been condensed for this entry and organized to progress in size from atomic scale to the macroscopic world of everyday experience.
Narrative:
Prologue [0:00]
The animation opens upon a single carbon atom, pulling back to reveal the DNA duplex of
which it is a part. As the view continues to expand, nucleosomes--the fundamental unit of
eukaryotic chromosomal organization, consisting of a complex of core proteins wrapped in
DNA--appear. Higher and higher levels of organization appear until entire chromosomes
are visible and it becomes clear that the scene is taking place in the nucleus of a eukaryotic cell. The cell is just completing a division and its chromosomes are still in a condensed, mitotic state. They will soon be unpacked into a loose tangle more suitable for carrying on their primary function of protein synthesis.
Protein production [0:22]
Regions of DNA that encode proteins, known as genes, are activated and inactivated
throughout development and adult life alike. This portion of the video provides an overview
of the complex series of events that begin with a genetic template for a protein and end with arrival of the newly-synthesized protein at its proper destination. These events can be grouped into four steps: (1) the copying of genetic information into a transcript; (2) the synthesis of a protein from instructions contained in the transcript; (3) the folding of the new protein into its proper conformation; and (4) the delivery of the mature protein to its appropriate destination in the cell.
The DNA duplex of one activated gene is pulled open within the active site of an RNA
Polymerase II (Pol II) complex in preparation for its use in the construction of a messenger RNA (mRNA) transcript that will guide the production of a specific protein: in this case, a transporter that permits chloride ions to be pumped out of a cell.
Pol II has mobile "jaws" that appear to help it advance along the DNA. Free nucleoside building blocks enter the active site through a pore in the back and are added to the growing RNA transcript. This transcript is quickly coated as it emerges from Pol II by ribonucleoprotein particles to prevent snarls that would result from hydrogen bonding
between its bases. After further processing to splice out unused segments called introns and to add a cap and tail, the transcript is ready to leave the nucleus and be translated into protein within the cytoplasmic compartment of the cell.
The RNA transcript nears a nuclear pore complex--the gateway to the cytoplasm--and is
escorted through by an exportin protein.
The video makes a short jump ahead at this time [1:18] to a point after the transcript has emerged into the cytoplasm, has assembled onto a ribosome and is beginning to be
translated into protein. Amino acids are added to the ribosome complex singly in a process
reminiscent of transcription to form a growing peptide chain in a sequence specified by the
mRNA transcript. Thus, the instructions contained within the original DNA duplex are used
to specify the pattern of the protein being made.
After a short stretch of polypeptide has been synthesized in the ribosome, a signal-anchor sequence of amino acids is created and bound by a signal recognition particle (SRP), drawing the polypeptide into a short loop and temporarily halting synthesis. The entire ribosomal complex diffuses to the endoplasmic reticulum (ER), where SRP and large ribosomal subunit bind to, respectively, a conjoined receptor and a membrane-spanning channel called a translocon. The emerging polypeptide strand is inserted as a loop into the translocon channel and thence across the ER membrane to anchor it.
As the ribosome continues to add amino acids to the elongating polypeptide strand,
additional signal-anchor sequences cause it to loop back and forth through the membrane.
The growing polypeptide rapidly assumes regions of secondary structure--alpha helices in
particular. Proteins that assist in folding the new protein, called molecular chaperones, bind transiently and repetitively on the cytoplasmic side to assist in proper folding of its domains, while another molecular assistant named calnexin contributes to proper folding from the luminal side. All this happens concurrently, so as the ribosome is synthesizing the last domains of the protein, the first are being folded.
When the final codon is reached, just a few bases from the end of the mRNA transcript,
release factors signal termination and dissociation of nascent protein from the mRNA and
ribosomal subunits.
The newly-completed chloride transporter, in this case a lung-specific protein known as
cystic fibrosis transmembrane conductance regulator, or CFTR, is delivered to the Golgi
complex as the first step of its journey to the plasma membrane through the secretory
pathway. After transiting the Golgi, it is packaged into a vesicle with other transporters
bound for the plasma membrane. This vesicle buds from the Golgi and diffuses a short
distance to a microtubule, is conveyed toward the apical surface of the cell by motor proteins and released near the plasma membrane. Fusion with the plasma membrane allows the
transporter to diffuse across its surface and begin transport of chloride ions out of the cell, a non-ciliated, cuboidal respiratory epithelial cell known as a Clara cell. The view transitions to a gradual withdrawal from the surface of our cell into the lumen of the pulmonary bronchiole of which it forms a part. Cilia on surrounding cells beat in unison within a thin, low-viscosity layer of fluid bathing the cells to move a highly-viscous adjacent layer of mucous and debris out of the airways.
Cell signaling [2:27]
In this scene, a motor neuron triggers the contraction of a muscle fiber. As the scene opens, an action potential is generated in a motor neuron and travels to its synapses on a muscle fiber. The camera closes in on a single synaptic bouton, showing the release of
neurotransmitter contents into the cleft of the neuromuscular junction, triggering a series of events that cause the release of calcium throughout the interior of the muscle fiber from intracellular stores. The sudden flood of Ca2+ into myofibrils--actin-myosin bundles constituting the contractile apparatus of the muscle fiber—initiates a stepwise relative movement of myosin and actin filaments, resulting in muscle contraction.
Embryonic Development and Organogenesis [3:08]
The animation opens on a scene taken from the first weeks of human life: a human zygote
has just undergone its third set of cell divisions and tumbles across the screen as a ball of eight cells. As it passes by, it develops into a hollow blastocyst, ultimately implanting in the uterine wall in its second week of life. The embryo continues its development over a two week time period, compressed into just a few seconds. It begins to develop eyes at around the end of its fourth week of life: first formed are the optic cups, which mold around invaginations of the overlying ectoderm called lens placodes. The lens placodes develop into lens vesicles and ultimately the lens; the optic cup develops multiple layers including retina, schlera and choroid. Vasculature develops to support the growing eye; eventually, internal vessels that fed the developing lens disappear. Meanwhile, the ectoderm invaginates a second time, giving rise to conjunctiva and later, the eyelids.
As the story draws to a close, we pass quickly through time to show the eye becoming that of a healthy three-year-old.
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