something zebra-fishy for At LO31113

From: ACampnona@aol.com
Date: 06/29/04


Dear Chris,

thank you once again for informing this forum publicly that At de
Lange has been unwell, again, and critically so. I am wondering what
territory he maps while he is in this zone and who maps his spirit as
it sits edgily there. i am sure there have been many messages of
goodwill and wellbecoming to both At and his family and friends.
Please accept mine here and now.

Tonight i was researching DNA Double Helix imagery and related
information,.... because i want to consider its relation to the
Argyris model of double loop learning and my own penchant for triple
and polylooped learning ;-)...during which searches i came upon this
(CUT and PASTED below;-)...i am not an expert on anything...but i
would be pleased if you'd let At see this when he is better.

I wonder who looks after his beloved fish while he is away?

love,
Andrew

http://mbbnet.umn.edu/doric/discoverygenomics.html

quoted from the paper above.

DNA on Tour & a "Tour de Force"

Back in the days when human chromosomes swam about the backdrop of my
mind like a screensaver, I remember reading a paper by Cold Spring
Harbor geneticist Barbara McClintock entitled "The Significance of the
Responses of the Genome to Challenge" [Science, 226:792, 1984]. It was
the paper she delivered in Stockholm, Sweden when she received the
Nobel Prize in 1983.

"In the future, attention undoubtedly will be centered on the genome,
and with greater appreciation of its significance as a highly
sensitive organ of the cell, monitoring genomic activities and
correcting common errors, sensing the unusual and unexpected events,
and responding to them, often by restructuring the genome," McClintock
wrote. "We know about the components of genomes that could be made
available for such restructuring."

One of the components constantly at work restructuring the genome,
which McClintock discovered while studying the genetics of corn (Zea
mays) in the 1940s, she called mobile or transposable elements.

These sequences of DNA-on-the-move, colloquially called "jumping
genes," burrow into the organism's chromosomes and produce everything
from "small changes involving a few nucleotides, to gross
modifications involving large segments of chromosomes, such as
duplications, deficiencies, inversions, and other more complex
reorganizations."

I was interested because I was studying so-called fragile sites in
human chromosomes. Fragile sites are specific places where chromosomes
break and fracture when the chromosomes are subjected to ionizing
radiation, chemical agents, or dietary deficiencies -- that is, when
they are subjected to environmental "challenge."

It is the genomic "transposable element," or transposon, that Hackett
and his scientific colleagues have recruited, refined and outfitted to
do the work of gene delivery.

In so doing, they have produced a practical tool for science, a great
promise for medicine, and a tour de force of creative ingenuity: the
"Sleeping Beauty Transposon System."

It began with zebrafish.

In 1994 scientists discovered transposons in zebrafish, proving that
"jumping genes" jumped in vertebrate genomes. The next year Hackett
and his colleagues reported that they had characterized a family of
transposons in Danio rerio. In some instances the transposons were
not evolutionarily conserved or embedded. That meant they could
potentially be "exploited for gene tagging and genome mapping."

That finding spurred them to take the next step. "We decided to make a
transposon ourselves," Hackett said.

They turned to the salmon family. Transposons were known to be more
active in salmon in recent evolutionary time than in zebrafish,
meaning they were less e mbedded. Using a "cut and paste" approach
that DNA transposons themselves use in moving around and across
genomes "in order to avoid extinction," Hackett and his postdoctoral
associates Zoltán Ivics and Zsuzsanna Izsvák set about to build a
transposon.

They identified and eliminated DNA sequences, accumulated through
evolution, that impaired the ability of the transposon to recognize
and bind to potential receptor molecules in the host genome. With
these out of the way, the transposon's enzymatic machinery -- its
transposases and integrases -- possessed the recognition sequences
they needed to carry out the binding, cutting and pasting in an
efficient manner.

The transposon engineered by Hackett and his colleagues took up
residence in fish and mammalian cells, including human cells. Its
frequency of uptake in cells could be increased many fold by combining
the transposon with a lipid.

The scientists dubbed their creation "Sleeping Beauty" because it was
"awakened from a long evolutionary sleep" in the salmon genome, with
the help, of course, of molecular tools, computer analysis, and
informed guesswork.

In their breakthrough paper, published in the journal Cell in 1997
["Molecular Reconstruction of Sleeping Beauty, a Tc1-like Transposon
from Fish, and its Transposition in Human Cells," 91: 501-510], they
observed that "Sleeping Beauty should prove useful as an efficient
vector for transposon tagging, enhancer trapping, and transgenesis in
species in which DNA transposon technology is currently not
available."

And for delivering therapeutic genes safely and effectively to
patients who need them.

 

-- 

ACampnona@aol.com

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