PAETE.ORG FORUMS
Paetenians Home on the Net

HOME | ABOUT PAETE | USAP PAETE MUNISIPYO  | MEMBERS ONLY  | PICTORIAL PAETE | SINING PAETE  | LINKS  |

FORUM GUIDELINES
please read before posting

USAP PAETE Forum Index USAP PAETE
Discussion Forums for the people of Paete, Laguna, Philippines
 
 FAQFAQ   SearchSearch    UsergroupsUsergroups   RegisterRegister 
 ProfileProfile   Log in to check your private messagesLog in to check your private messages   Log inLog in 

(Bio) (Chem) DNA Used Like Velcro to Make Cells Stick
Goto page 1, 2  Next
 
Post new topic   Reply to topic   printer-friendly view    USAP PAETE Forum Index -> Science Lessons Forum
View previous topic :: View next topic  
Author Message
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Mon Feb 13, 2006 8:45 pm    Post subject: (Bio) (Chem) DNA Used Like Velcro to Make Cells Stick Reply with quote






DNA Used Like Velcro to Make Cells Stick
By Corey Binns
Special to LiveScience
posted: 13 February 2006
08:36 am ET

Devices made of living cells promise to one day improve drug screening, virus detection and the growing of artificial tissue.

First scientists have to overcome a significant hurdle. Some cell surfaces, like blood cells, are nature's version of Teflon. Their slippery nature makes it impossible to hook them up with non-biological material.

But put a piece of DNA on its surface, and a cell looses its slick, scientists have discovered.

"We figured out a way to get living cells to attach where and when we want them to," said study lead author Ravi Chandra, a chemist at the University of California at Berkeley.

Normally, DNA lives inside a cell's nucleus. The Berkeley team created a chemical reaction to link a strand of DNA onto a cell's surface. They could then dictate where the cell would stick by putting a complementary piece of DNA, essentially a recognition partner, at the designated site.

Only cells with the DNA that matched the complementary DNA stayed put.

The research is detailed in the latest issue of the international chemistry journal Angewandte Chemie.

"Now we'll see if we can harness some of the cells' power by incorporating them into a device," Chandra told LiveScience.

A device or chip with living cells on it might someday be useful for the military, homeland security, or people who study immune diseases.

Say a postal worker finds white powder spilling out of an envelope. To determine whether the white powder was anthrax or just some crumbled piece of sidewalk chalk, a scientist could use a cell chip. Carefully placed immune cells would be stuck on the chip. Our immune cells are programmed to recognize specific carriers of disease and initiate an immune system response.

The specific cells on the chip could recognize anthrax, and their response to the white powder would signal to scientists whether or not it was harmful.

The cell chip is in our future, Chandra said. The question is how soon. "These are not science fiction applications."

*************************************************************

Questions to explore further this topic:

What are the parts of a cell?

http://gslc.genetics.utah.edu/units/basics/cell/

What is DNA?

http://www.eurekascience.com/I....._intro.htm
http://gslc.genetics.utah.edu/units/basics/tour/
http://blairgenealogy.com/dna/dna101.html
http://www.ncc.gmu.edu/dna/introduc.htm

What is the structure of DNA?

http://www.accessexcellence.or.....cture.html
http://www.blc.arizona.edu/Mol.....orial.HTML
http://www.johnkyrk.com/DNAanatomy.html

How is a DNA molecule built?

http://gslc.genetics.utah.edu/...../builddna/

Where is DNA found?

http://gslc.genetics.utah.edu/.....xtraction/
http://www.pbs.org/wgbh/aso/tryit/dna/woundup.html

How big is DNA?

http://www.thetech.org/genetics/zoomIn/index.html

You can make a model of DNA out of paper

http://www.dnai.org/teachergui.....i_inst.pdf

What is the function of DNA?

http://www.thetech.org/exhibit.....ne/genome/
http://gslc.genetics.utah.edu/.....ypatterns/
http://news.bbc.co.uk/hi/engli.....efault.stm

What carries hereditary information from one generation to the next?

http://www.dnai.org/a/index.html

History of DNA research?

http://www.pbs.org/wnet/dna/episode1/index.html
http://www.dnai.org/timeline/index.html
http://osulibrary.orst.edu/spe.....uling/dna/

How is DNA decoded by scientists?

http://news.bbc.co.uk/hi/engli.....efault.stm

How do scientists study DNA?

http://www.dnalc.org/ddnalc/re.....tions.html

How is DNA replicated?

http://www.pbs.org/wgbh/aso/tr.....ation.html
http://www.johnkyrk.com/DNAreplication.html
http://www.ncc.gmu.edu/dna/repanim.htm

What is a gene?

http://www.thetech.org/genetics/feature.php
http://www.dnaftb.org/dnaftb/1/concept/

How are genes transcribed and translated?

http://gslc.genetics.utah.edu/.....ranscribe/

What is a genome?

http://www.dnai.org/c/index.html

What are chromosomes?

http://www.dnalc.org/ddnalc/resources/chr11a.html

Take a virtual tour of a gene research center (Stanford)

http://www.thetech.org/genetic...../shgc.html

Can we manipulate genes?

http://www.dnai.org/b/index.html

Are there genetically modified food?

http://www.thetech.org/genetic.....foods.html
http://www.geo-pie.cornell.edu/crops/eating.html

What are some of the applications of DNA science?

http://www.dnai.org/d/index.html
http://www.koshland-science-mu...../index.jsp
http://www.scientific.org/tuto.....riley.html
http://news.nationalgeographic.....puter.html

What is eugenics?

http://www.dnai.org/e/index.html

Is genetic research controversial?

http://library.thinkquest.org/C004367/be10.shtml

GAMES

http://www.genecrc.org/site/ko/index_ko.htm
http://genetics.gsk.com/kids/
http://www.pbs.org/wgbh/aso/tryit/dna/


Last edited by adedios on Sat Jan 27, 2007 3:53 pm; edited 2 times in total
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Mon May 29, 2006 9:30 am    Post subject: Genes: The Instruction Manuals for Life Reply with quote

Genes: The Instruction Manuals for Life

By Corey Binns
Special to LiveScience
posted: 29 May 2006
08:01 am ET



A gene is a how-to book for making one product—a protein.

Proteins perform most life functions, and make up almost all cellular structures. Genes control everything from hair color to blood sugar by telling cells which proteins to make, how much, when, and where.

Mystery Monday
Each Monday, this LiveScience series explores an amazing aspect of the world around you.

Genes exist in most cells. Inside a cell is a long strand of the chemical DNA (deoxyribonucleic acid). A DNA sequence is a specific lineup of chemical base pairs along its strand. The part of DNA that determines what protein to produce and when, is called a gene.

Full article:

http://www.livescience.com/hum.....genes.html
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Mon Jul 17, 2006 6:54 pm    Post subject: Molecular DNA Switch Found to be the Same for All Life Reply with quote

July 17, 2006
Molecular DNA Switch Found to be the Same for All Life
Lawrence Berkeley National Laboratory

BERKELEY, CA —The molecular machinery that starts the process by which a biological cell divides into two identical daughter cells apparently worked so well early on that evolution has conserved it across the eons in all forms of life on Earth. Researchers with the U.S. Department of Energy’s Lawrence Berkeley National Laboratory and the University of California at Berkeley have shown that the core machinery for initiating DNA replication is the same for all three domains of life - Archaea, Bacteria and Eukarya.

For the full article:

http://www.lbl.gov/Science-Art.....r-DNA.html
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Mon Jul 24, 2006 4:23 pm    Post subject: It's all in the genes Reply with quote

Northern Arizona University
24 July 2006

It's all in the genes

Landmark research shows genetic link to community makeup and ecosystem evolution
It's common knowledge that genes control traits such as eye and hair color. But a large group of scientists from two continents has found that the genes of one organism not only control the characteristics of that individual but also dictate the behavior of thousands of other organisms in a community.
They say these genes, in fact, influence the evolution of an entire ecosystem.

"We're pushing a whole new field of research," said lead investigator Tom Whitham, Regents Professor of biological sciences at Northern Arizona University.

It's a field that has not been explored before. After all, the idea of looking at the genes of thousands of species in even a simple community is daunting at best.

"What we've done is zero in on a foundation species, because not all species are as equally important ecologically," Whitham said. The foundation, or key, species in this case is the cottonwood tree, which is the first tree to have all its genes sequenced, or mapped.

Among the genes under study are those that control the level of tannins in cottonwoods, which are dominant trees in riparian habitats in the West. Different individuals, or genotypes, of cottonwoods have different levels of tannins.

These genetically controlled tannin levels drive the structure--or phenotype--of a riparian forest, according to Whitham. Tannins affect the decomposition rate of cottonwood leaves, which in turn affects the fertility of soils, which affects the microbes in the soil, which affect the insects that live in the soil or eat the leaves, which affect the birds that feed on the insects, and so on.

In the July issue of Nature Reviews Genetics and the May issue of Evolution, Whitham and fellow researchers discuss how this phenotype is heritable on an ecosystem level. That is, the progeny of a tree are likely to support the same communities of organisms and ecosystem processes that their parents supported.

It's a premise with far-reaching implications. Consider, for example, conservation efforts to preserve biodiversity in the face of habitat destruction, climate change and other impacts on the environment. Planting trees that are genetically diverse will result in increased diversity of other species in the dependent community. The greater the tree diversity, the greater the chance of associated species surviving environmental degradation.

"It's not enough to save rare and endangered species. We need to save genetic diversity in the foundation species," said Jennifer Schweitzer, a co-author of the Nature Reviews Genetics paper and postdoctoral researcher at NAU. "Having high genetic diversity in these foundation species is insurance against changes in the future."

The research also has ramifications when it comes to genetically modified organisms and their effects on the landscapes in which they are introduced. For example, grasses that are genetically altered to prevent weed growth could pass that resistance along to exotic plants, which then might take over a community and change the evolution of that ecosystem.

More than 50 researchers from the United States, Canada and Australia are studying this genetic driver of community structure and ecosystem evolution. The work is funded by a $5 million Frontiers in Integrative Biological Research grant from the National Science Foundation. The project includes scientists from a multitude of disciplines because, as Whitham says, "No one person has all the skills to do this."

"This is an exciting project with global impact, drawing on the expertise of geneticists, ecologists, molecular biologists, biogeographers and others," said Chris Greer, program director at the National Science Foundation. "The results are expected to not only shed light on how complex biological communities function but to inform efforts to address the impact of human activities, such as landscape fragmentation, on stressed ecosystems across the planet."

The researchers are the first to study the genetic framework of communities and ecosystems in the wild. They have planted several experimental "common gardens" of cottonwoods in Arizona and Utah. The trees are propagated at NAU's research greenhouse. Through DNA fingerprinting, the scientists know the precise genetic makeup of each tree.

In one experiment, Whitham's group worked with the Bureau of Reclamation to plant about 10,000 trees at the Cibola National Wildlife Refuge along the lower Colorado River, about 20 miles south of Blythe, Calif., to examine how genetic diversity at the stand level influences communities and ecosystem processes.

"The Bureau of Reclamation gets restoration out of this project, and we get this incredible experiment," said Whitham.

All of the experiments, so far, have exceeded the researchers' expectations. "Initially we thought that the [genetic influences] would be more localized--that the influences would be less genetic and more environmental as we moved beyond the local common garden setting to all of the western U.S." In the end, however, Whitham said, "Plant genes are far more important than we ever expected them to be."

Now the researchers want to know if their findings hold true in different environments around the world. "To understand how important something is, you have to test in multiple locations," Whitham said.

A parallel study in Australia that examines the eucalyptus tree as the foundation species is yielding the same results as the studies on cottonwoods. And Whitham has just returned from South Africa and Borneo in Southeast Asia, where he is planting the seeds for further study.
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Tue Aug 08, 2006 7:16 am    Post subject: Surprise Finding For Stretched DNA Reply with quote

Surprise Finding For Stretched DNA
Berkeley Laboratory
7 August 2006

BERKELEY, CA — Most of us are familiar with the winding staircase image of DNA, the repository of a biological cell’s genetic information. But few of us realize just how tightly that famous double helix is wound. Stretched to its full length, a single molecule of human DNA extends more than three feet, but, when wound up inside the nucleus of a cell, that same molecule measures about one millionth of an inch across. Biologists have long believed that as a molecule of DNA is stretched, its double helix starts to unwind. As much sense as this makes from an intuitive standpoint, a recent experiment proved it not to be the case.

For the full article:

http://www.lbl.gov/Science-Art.....d-DNA.html
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Thu Aug 17, 2006 7:33 am    Post subject: DNA in Urine Can Reveal Disease Reply with quote

DNA in Urine Can Reveal Disease

By Charles Q. Choi
Special to LiveScience
posted: 16 August 2006
09:29 am ET



Simple urine tests for DNA fragments could help in the early detection of cancer, tuberculosis, HIV, malaria and potentially many other diseases.

Such tests might eventually also uncover rejection of transplanted organs before symptoms of inflammation manifest or genetically test fetuses for birth defects.

A decade ago, cell biologist David Tomei, CEO of New York molecular diagnostic company Xenomics, and his colleagues were the first to report that short fragments of DNA from throughout the body could cross the kidney's filters into urine.

For the full article:

http://www.livescience.com/hum.....urine.html
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Thu Aug 24, 2006 10:30 am    Post subject: Scientists Uncover Critical Step in DNA Mutation Reply with quote

Scientists Uncover Critical Step in DNA Mutation
Georgia Institute of Technology

Atlanta (August 23, 2006) — Scientists at the Georgia Institute of Technology have made an important step toward solving a critical puzzle relating to a chemical reaction that leads to DNA mutation, which underlies many forms of cancer. The research, which uncovers knowledge that could be critical to the development of strategies for cancer prevention and treatment, appears in the August 2006 edition (Volume 128, issue 33) of the Journal of the American Chemical Society.

For the full article:

http://www.gatech.edu/news-roo.....hp?id=1106
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Wed Aug 30, 2006 4:18 pm    Post subject: DNA evidence in paternity cases Reply with quote

DNA evidence in paternity cases
STAR SCIENCE By Maria Corazon A. De Ungria, Ph.D.
The Philippine STAR 08/31/2006
http://www.philstar.com/philst.....314402.htm

Deoxyribonucleic acid or DNA testing is the most accurate form of testing to
prove paternity or exclude paternity when the identity of the biological
father is under dispute. DNA-based paternity testing has been requested to
support claims for child support, inheritance, immigration and for peace in
the family. More recently, DNA tests have been used to dispute false
paternity claims that have already been decided in favor of the child's
mother prior to the submission of DNA evidence in US courts.

Traditionally, paternity is determined using evidence derived from the
woman's testimony, the defense of the alleged father where he claims
sterility or that another man had had relations with the child's mother, a
presumption of legitimacy if the child was born within a valid marriage and
physical resemblance between the putative father and the supposed child. In
addition, either party may present the results of serological tests, e.g.
ABO and MN blood typing, to support their respective claims.

In more recent years, the use of selected DNA markers has become the
procedure of choice over blood typing because of the increased level of
polymorphism and the less susceptibility of DNA molecules to degradation
compared to proteins. The molecular stability of DNA is particularly
important when dealing with environmentally challenged samples, e.g. exhumed
bones and degraded tissues. Of the different methods of DNA analysis, STR
(Short Tandem Repeat) typing is currently the most widely used because this
method allows unambiguous scoring of DNA profiles, rapid processing and
analysis.

DNA typing for paternity is done by first carefully extracting the DNA from
the biological samples submitted by the alleged father, child with mother
(paternity trio) or in the absence of the mother's sample (paternity duo).
The DNA pattern from the child is analyzed given those of his mother (if
available) and alleged father. The DNA type contributed by the child's real
biological father should be observed in the alleged father. Then, the
probability that the alleged father is the father of the child is calculated
as a ratio between that of the alleged father and any random male in the
population. Notably, testing without the mother's DNA profile (motherless
case) was found to be less informative and five times more prone to
paternity inclusions when testing seven STR markers than when the maternal
DNA profile is made available. The current DNA Laboratory set-up at UP-NSRI
Diliman campus uses 16-20 STR analysis which includes the FBI-defined
Combined DNA Identification System (CODIS) markers for DNA typing
(www.dnaforensic.org). At the UP-NSRI DNA Laboratory, the lack of
information brought about the absence of the mother's DNA profile in
motherless cases is minimized by increasing the number of DNA markers of the
alleged father and child that are tested to 20 markers compared to the
standard 16 markers for paternity trio cases.

A mismatch suggests that the alleged father is excluded as the biological
father of the child. In some cases, mutation results in a false mismatch
between real fathers and their children, hence the standard accepted in most
laboratories is to require a minimum of two mismatches prior to excluding a
man from potentially fathering the child. On the other hand, a match between
the DNA profile of the alleged father and the child does not necessarily
establish paternity, but may be due to chance matches between totally
unrelated individuals. To estimate the likelihood of paternity over
non-paternity, a Probability of Paternity (W) is calculated based on the DNA
profile of the father, mother and child. The Supreme Court prescribed the
minimum value of 99.9 percent for W.

Although the resolution of questioned paternity is normally a civil issue,
it may also play an important role in criminal cases such as those involving
rape when the victim also claims that the accused is the father of her child
born out of the rape (criminal paternity). The first such case where DNA
evidence was used was People v Paras (1999) where blood typing and DNA
profiling results conclusively excluded the accused from being the father of
the victim's child. To the trial court, the date of the last incidence of
rape stated by the victim is important since the child was born 10 months
after the said date. According to the trial court, "these facts would be in
violation of the rule of nature."

With the rapid development of DNA-based paternity testing, it is inevitable
that DNA evidence will be used more and more to support or argue against
paternity in the courts of law. Initially, the strength of paternity tests
lies primarily in its power to exclude the wrong man. However, the rapid
development of STR typing technology has also increased its power to
identify real fathers, thus providing objective evidence for a fair and
swift resolution of civil and criminal cases.
* * *
Dr. Maria Corazon A. de Ungria currently heads the DNA Analysis Laboratory
of the Natural Sciences Research Institute, University of the Philippines,
Diliman campus (www.dnaforensic.org). This laboratory is currently promoting
the development of forensic DNA technology in the country as well as the
conduct of genetic studies of different Philippine populations.

Since 1998, the UP-NSRI DNA lab has been accepting requests for DNA typing
in disputed parentage cases as well as assistance in criminal cases. Dr. De
Ungria has received recognition from the scientific community as well as lay
organizations for her various research endeavors, the results of which are
aimed at putting science at the service of society.

Her awards include the Outstanding Young Scientist (OYS) award in 2003 from
the National Academy of Science and Technology (NAST) and the UP
Chancellor's Gawad Hall of Fame for Best REPS in Research in 2005 from the
University of the Philippines (Diliman). In 2005, she was the only woman who
won one of The Outstanding Young Men (TOYM) award given by the Philippine
Jaycees and TOYM Foundation as well as the Gerry Roxas Leadership Award from
the Gerry Roxas Foundation.
Back to top
View user's profile Send private message Visit poster's website
jilbruke
Guest





PostPosted: Fri Sep 08, 2006 4:47 am    Post subject: Reading, decoding, and simulating the being from it's DNA Reply with quote

Hi I've been looking around for a while for information regarding how genetic data is being used. Not from a social perspective but a technical one. You seem to be a vocal expert in the field or at least be in constant contact with as much. As such I thought I'd pose the questions that I developed.

1. Do we currently know enough to model an entire human DNA strand on the molecular level? As an aside does each DNA strand have exactly the same number of links?

2. If we have this information, then do we know exactly how the DNA is interpreted by the cells to reproduce?

3. If we know the micro chemical/mechanical process that reads the chain and builds more cells, can we, from the structure of an entire cell, predict what the cell looks like and how it interacts with other cells?

4. Given we know this much, can we simulate the process via computer, and from a DNA strand interpret the form it takes?

This process is exactly the same as how a computer takes a file, a linear binary sequence, and using the appropriate interpretations produces a unique and meaningful result, however, somewhat more complicated. However the speed at which files of billions of bits are interpreted shows some promise to the feasibility of the idea.

Understandably there is a lot of assumed information and issues with this theory, I've thought of these so far:

Every translation mechanism may be different between each species and even each example of a species, where the translator's form is dictated by the DNA also... This makes the discovery process circular and makes it impossible.

A DNA strand may not have one unique resulting being, based on factors I haven't considered or don't know about...

As an engineer working in the field of comupter simulation, I'm fascinated by the idea of the DNA and DNA decoding mechanism being simulated with a resulting form being predicted. With this a test case could predict the form of a microorganism from its DNA, eventually an entire living human too. The ultimate result would be to put the DNA of a non-living being through the translation to predict the form of beings many thousands of years old.

Thanks for your time, please pass this onto anyone who might have an interest in the idea,
Jilbruke Collins
Back to top
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Thu Sep 21, 2006 8:02 pm    Post subject: Watching DNA Repair in Real Time Reply with quote

Watching DNA Repair in Real Time
September 20, 2006
UC Davis


Direct observations of DNA are giving new insights into how genetic material is copied and repaired.

"We can monitor the process directly, and that gives us a different perspective," said Roberto Galletto, a postdoctoral scholar at UC Davis and first author on a paper published Sept. 20 on the Web site of the journal Nature.

In E. coli bacteria, molecules of an enzyme called RecA attach themselves along a DNA strand, stretching it out and forming a filament. A piece of complementary DNA lines up along side it, and pieces of DNA can be swapped in to repair gaps in the original strand. A similar protein, called Rad51, does the same job in humans.

"How RecA and Rad51 assemble into filaments determines the outcome of DNA repair, but very little is known about how assembly is controlled," said senior author Stephen Kowalczykowski, professor in the sections of Microbiology and of Molecular and Cellular Biology and director of the Center for Genetics and Development at UC Davis. Genes that control the human gene, Rad51, have been linked to increased risk of breast cancer.

Galletto attached a short piece of DNA to a tiny latex bead and placed it in a flow chamber, held by laser beam "tweezers." Fluid flowing past made the DNA stream out like a banner. Then he nudged it into an adjacent channel containing fluorescently-tagged RecA. After short intervals of time, he moved it back to the first chamber to observe the results.

By repeatedly dipping the same piece of DNA into the fluorescent channel, the researchers could see the RecA form clusters of four to five molecules on the DNA. Once those clusters had formed, the DNA/RecA filament rapidly grew in both directions. The measurements made in those experiments will be the baseline for future studies of both RecA and Rad51, Kowalczykowski said.

The new work adapts an approach developed by Kowalczykowski and Ronald J. Baskin, professor of molecular and cellular biology, to study single enzymes at work unwinding DNA strands. That research was first published in Nature in 2001.

In addition to Galletto, Kowalczykowski and Baskin, the research team included postdoctoral scholar Ichiro Amitani. The work was funded by the National Institutes of Health and a fellowship awarded to Galletto by the Jeane B. Kempner Foundation.
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Wed Oct 04, 2006 10:06 am    Post subject: Investigator seeks to uncover roots of DNA’s ‘sweet’ secret Reply with quote

Investigator seeks to uncover roots of DNA’s ‘sweet’ secret

September 29, 2006

by Melissa Marino

DNA's simple and elegant structure — the “twisted ladder,” with sugar-phosphate chains making up the “rails” and oxygen- and nitrogen-containing chemical “rungs” tenuously uniting the two halves — seems to be the work of an accomplished sculptor.

For the full article:

http://www.mc.vanderbilt.edu/r.....ml?ID=5043
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Wed Nov 01, 2006 11:14 am    Post subject: Excitement and opportunities in systems biology Reply with quote

Excitement and opportunities in systems biology
STAR SCIENCE By Baltazar D. Aguda, PhD
The Philippine STAR 11/02/2006

Not so many years ago, in February 2001, two groups in the US published the first drafts of the human genome sequence in the journals Nature and Science. The sequence is that of approximately three billion "letters" that run through strands of DNA, the primary component of our chromosomes where our genes reside. It has been known for a long time that a DNA letter can only be one of four – namely, A, T, C, or G – and it never ceases to amaze me that the linear sequence of these letters contains virtually all the information required to create a complex organism like us (see note [1] at the end of the article for meaning of acronyms). Recent estimates on human genes put their number at about 30,000, which corresponds to how many proteins our cells can make. The translation of the sequence of DNA letters to proteins requires the so-called "genetic code" that instructs cells what amino acids (the components of proteins) should be assembled for a given sequence of letters. The elucidation of the genetic code and understanding the molecular machinery for expressing genes to proteins are major achievements of molecular biology. The proteins are the workhorses of cells; they carry out various enzymatic functions such as catalyzing metabolic reactions, structural functions such as those of protein filaments and other cellular fibers, and they orchestrate physiological processes such as cell division and differentiation. So this means that the human genome sequence information tells us everything we need to know about human biology, right? Wrong.

To be fair, it is perfectly understandable why we should be excited by the availability of a human genome sequence. If we know where the genes and their sequences are, we can compare a normal gene from a mutated one (having at least one letter changed in the sequence), analyze the changes in the expressed protein and then predict the consequences of this mutation on human health. A classic example is a mutation in the hemoglobin gene – namely, a specific GAG sequence in the gene is changed to GTG – which leads to the disease called sickle-cell anemia. So it is easy to see why there is a lot of expectation regarding the utility of the genome sequence toward developing cures for genetic diseases.

The discipline called Bioinformatics is concerned with the analysis of genome sequences, including discovering genes in the three-billion letter sequence of human DNA – work that is far from complete. But even when we get to know all of our genes, a far more daunting task will still be ahead of us. Genes can be turned "on" or "off" – meaning that they may or may not be producing proteins. It is the regulation of gene expression that is turning out to be horrendously complex. The making of proteins from DNA actually occurs via another class of molecules called RNA (see note [1]). A gene sequence on the DNA is "transcribed" to the corresponding RNA molecule, and this RNA is "translated" to the protein. The complexity stems from the fact that information flow is not linear. Many proteins can bind to DNA and affect RNA transcription. Many proteins can also bind to RNA and influence the protein translation process. RNA molecules can also affect both transcriptional and translational processes. And as if the picture is not complex enough, proteins interact with other proteins, with metabolites or other molecules when they carry out their cellular functions. How are we to cope with such complexity? First, we try to identify and classify all the players in the system. We are in the era of Omics revolutions brought about by high-throughput data-acquisition technologies. Genomics is churning out genome sequences of hundreds of organisms; transcriptomics is developing microarray technologies that monitor RNA levels (the transcriptome); and proteomics aims to identify and characterize the set of cellular proteins (the proteome). There is also metabolomics which aims to measure all the metabolites produced in a cell, and interactomics which assays protein-protein and other molecular interactions (yes, scientists do get carried away!). Essentially these Omics will provide us with a comprehensive parts list of our cells. Secondly, it will be the integration of these parts and the analysis of the dynamics of their interactions that ultimately will bring about a comprehensive understanding of biological systems – this is where Systems Biology enters the picture.

The basic premise of Systems Biology is that the whole is greater than the sum of its parts. In other words, there are properties attributed to the system as a whole which cannot be predicted from studying the parts in isolation because these properties emerge from the interactions of the parts. An unmistakable attribute of Systems Biology is that it is interdisciplinary. The complexity of biological systems demands collaboration among biologists, chemists, physicists, mathematicians, computer scientists, etc.; this explains the recent proliferation of institutes of systems biology in North America, Europe, and Japan.

I was trained as a physical chemist in graduate school, and taught university chemistry courses for many years. After getting my tenure in the late 1990s, and with all the buzz about genomics and transcriptomics at that time, I saw the opportunity of refocusing my research to join in the fun. My re-education in molecular cell biology was wonderfully quick and painless – thanks to the excellent Internet infrastructure in my university. I cannot overemphasize this enough: the Internet is a great global equalizer in scientific research. With a good connection, anybody in the world can access a universe of information, instantly. There are many free or open-access online scientific journals (see note [2]) and downloadable lecture notes and videos from eminent academic institutions such as the Massachusetts Institute of Technology in the US (for the open courseware, see note [3]). There are even popular biology textbooks that one can access online (see note [4]). To tell you the truth, I hardly go to our library now because Google searching (see note [5]) is often sufficient! However, it is always a good practice to double check information obtained from the Web.

My pet research project is in an area called cancer systems biology. Cancer is a complex disease involving the interplay among many cellular processes, including the cell division cycle, apoptosis (programmed cell death), angiogenesis (formation of blood vessels required to feed tumors), senescence (aging of cells), and others. Years of research in the cancer community, and more recently the abovementioned Omics technologies, are providing unprecedented details of relevant molecular pathways. For those interested in cellular pathways in general, visit pathguide (see note [6]) to access over 200 databases of biological pathways. I think the analysis of these pathways is where a lot of research and business opportunities lie, not just in cancer research but also in understanding other human diseases. It is no surprise that big pharmaceutical companies are keenly interested in reliable pathways databases and are actively developing computer software for analyzing these pathways. Sprouting from academia in the US are biotech companies that are established very cheaply by a few smart students with modest computing power (visit, for example, the website given in note [7]). I believe that smart students in the Philippines can do the same. At the moment, a key problem in using online pathways databases is how to integrate them, cope with the uncertainties in the data, and extract network models for diseases of interest. In a recent international bioinformatics conference held in Brazil (see note [8]), I presented my ideas on this issue in a set of tutorial lectures which can be downloaded from the website given in note [9]. There is an urgent need for a network analysis software that could identify drug targets. I think multi-drug therapeutic strategies will be the answer for cancer, and for many other diseases.

In some of those regular Friday night gatherings (of UPLB Chemical Society members) when I was still an undergraduate at the University of the Philippines at Los Baños (to play bidding bridge, the Society’s unofficial card game at that time), I recall asking the question, "How can inanimate molecules organize and interact to create life?" Although I may not have been conscious about it, the longing for an answer steered the education and research I have pursued for almost three decades. My naivete was exposed as the years went by and I became more skeptical that I would ever hear an answer in my lifetime – until recently, when my optimism began to build up into excitement because I feel that the systems biology approach may ultimately provide us the opportunity to formulate a good answer. * * *
Notes:

[1] DNA = deoxyribonucleic acid; "letters" A, T, C, G correspond to the first letter of the following chemical bases: adenine, thymine, cytosine, guanine. RNA = ribonucleic acid.

[2] http://www.plos.org and http://www.biomedcentral.com

[3] http://ocw.mit.edu

[4] http://www.ncbi.nlm.nih.gov/en.....i?db=Books

[5] http://www.google.com

[6] http://www.pathguide.org

[7] http://www.gnsbiotech.com

[8] http://www.ismb2006.cbi.cnptia.....rials.html

[9] http://www.mbi.ohio-state.edu/.....b2006.html

* * *
Dr. Baltazar Aguda is currently a visiting scholar at the Mathematical Biosciences Institute, Ohio State University, USA where he is writing a book on mathematical models of cell-fate regulation. He obtained his PhD in Chemistry (chemical physics program) in 1986 from the University of Alberta (Canada) and his BSc Agricultural Chemistry degree from the University of the Philippines at Los Baños in 1978. He can be e-mailed at bdaguda@gmail.com.
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Mon Nov 13, 2006 10:55 am    Post subject: Solving the structure of xDNA Reply with quote

Solving the structure of xDNA
Journal of the American Chemical Society
13 November 2006

James Watson and Francis Crick deciphered the structure of regular DNA 53 years ago. Now, scientists from Stanford University have determined the structure of xDNA. That's "expanded DNA," a strange double helix molecule that is 20 percent wider and more heat-resistant than natural DNA. Inherently fluorescent, expanded DNA glows in ways that may make xDNA useful as a medical and scientific probe.

Eric T. Kool and colleagues developed xDNA in 2003 by adding a benzene ring to the chemical bases that form natural DNA. Natural DNA, which is 20 angstroms wide, and benzene, with a girth of 2.4 angstroms, produced the wholly new wider double helix. The researchers now have combined all four expanded DNA bases with the four natural DNA bases to produce a complete eight-base molecule. They then used nuclear magnetic resonance to reveal the structure of xDNA and study the molecule.

In an article scheduled for publication Nov. 22 in the weekly Journal of the American Chemical Society, they describe the features needed for DNA that encodes and transfers genetic information. They report: "The present work shows that the eight-base xDNA system may have most if not all of these features, which suggests the future possibility of a functioning, replicable genetic system using xDNA as the genetic material."

ARTICLE #4
"Toward a Designed, Functioning Genetic System With Expanded-Size Base Pairs: Solution Structure of the Eight-Base xDNA Double Helix"

DOWNLOAD PDF
http://pubs.acs.org/cgi-bin/sa.....65606n.pdf
DOWNLOAD HTML
http://pubs.acs.org/cgi-bin/sa.....5606n.html
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Fri Feb 02, 2007 7:55 am    Post subject: Scientists See DNA Get 'Sunburned' for the First Time Reply with quote

SCIENTISTS SEE DNA GET "SUNBURNED" FOR THE FIRST TIME
1 February 2007
Ohio State University

COLUMBUS , Ohio – For the first time, scientists have observed DNA being damaged by ultraviolet (UV) light.

Ohio State University chemists and their colleagues in Germany used a special technique to watch strands of DNA in the laboratory sustain damage in real time.

They observed the most common chemical reaction among a family of reactions on the DNA molecule that are linked to sunburn, and discovered that this key reaction happens with astounding speed -- in less than one picosecond, or one millionth of one millionth of a second.

Scientists are studying UV damage to understand the role it plays in sunburn and diseases such as skin cancer. This new finding, reported in the current issue of the journal Science, shows that the damage depends greatly on the position of the DNA at the moment the UV strikes the molecule.

UV light excites the DNA molecule by adding energy, said Bern Kohler, associate professor of chemistry at Ohio State. Some exited energy states last a long time, and others a short time. The energy often decays away harmlessly, but occasionally it triggers a chemical reaction that alters the DNA's molecular structure.


--------------------------------------------------------------------------------

They examined damage to isolated DNA strands, not DNA within a cell. Sunburn results from a series of chemical reactions in a living cell, and so this experiment did not allow them to see a cell sustain sunburn. This is, however, the first time anyone has observed the initial molecular events behind damage to DNA.
--------------------------------------------------------------------------------

Previously, scientists believed that the longer a DNA molecule was excited by UV energy, the greater the chance that it would sustain damage. So long-lived excited states were thought to be more dangerous than short-lived ones. But this study shows that the most common UV damage is caused by a very short-lived excited state.

"The speed of this reaction has important consequences for understanding how DNA is damaged by UV light," said Kohler. "In this study, we didn't see any evidence that long-lived energy states are responsible for damage. Now it seems more likely that short-lived states cause the most common chemical damage to DNA."

That damage consists of two tiny molecular bonds that form where they shouldn't -- between two thymine bases stacked together among the billions of bases in the DNA double helix.

DNA employs some chemical reactions of its own to heal itself. But when DNA sustains too much damage, it can't replicate properly. Badly damaged cells simply die -- the effect that gives sunburn its sting. Scientists also believe that chronic damage creates mutations that lead to diseases such as skin cancer.

For this study, the chemists used a technique called transient absorption to observe the DNA damage. Transient absorption is based on the idea that molecules absorb light at specific wavelengths, and it allows researchers to study events that happen in less than a picosecond.

They took specially designed strands of DNA -- ones made solely of thymine bases, in order to boost the chance of observing a reaction between adjacent thymines -- and exposed them to UV light. Then they timed the reactions that caused the new thymine bonds to form.

Kohler stressed that he and his colleagues examined damage to isolated DNA strands, not DNA within a cell. Sunburn results from a series of chemical reactions in a living cell, and so this experiment did not allow them to see a cell sustain sunburn.

This is, however, the first time anyone has observed the initial molecular events behind damage to DNA. Kohler thinks the results might make scientists attack the problem of UV damage in a new way.

DNA in a cell is always moving, he explained. It bends and twists one way or another because it is a relatively flexible molecule. This flexibility enables the normal chemical reactions that are constantly happening in the cell. Each shape-shift can require anywhere from a few to several hundred picoseconds to complete.

That's fast, but this new study shows that UV damage happens many times faster. On the timescale that the unwanted bonds form, even a rapidly moving DNA molecule would essentially appear frozen.

That means that whether or not two thymine bases are damaged depends on the position of the DNA during the extremely brief time required for it to absorb UV light. Either two thymine bases are lined up in just the right way to bond when the UV hits, or they're not.

"This insight explains why some pairs of thymine bases get damaged more frequently than others, and it suggests that scientists can understand damage patterns to DNA by studying the factors that influence how the bases are arranged in space," Kohler said.

"In our efforts to understand photo-damage, this new result shifts our attention to the DNA structure, and the kinds of arrangements that exist at the moment DNA absorbs light."

His coauthors on the paper include Carlos E. Crespo-Hernandez, a former postdoctoral researcher at Ohio State ; and Wolfgang J. Schreier, Tobias E. Schrader, Florian O. Koller, Peter Gilch, Wolfgang Zinth, Vijay N. Swaminathan, and Thomas Carell, all of Ludwig Maximilians University in Munich .

The research was funded in part by the National Institute of General Medical Science at the National Institutes of Health, and by the Alexander von Humboldt Foundation of Germany.
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Fri Feb 09, 2007 10:22 am    Post subject: Genographic Project Reply with quote

The National Geographic Society, IBM, geneticist Spencer Wells, and the Waitt Family Foundation have launched the Genographic Project, a five-year effort to understand the human journey—where we came from and how we got to where we live today. This unprecedented effort will map humanity's genetic journey through the ages.

The website:

https://www3.nationalgeographic.com/genographic/index.html

An overview of genetics

https://www3.nationalgeographic.com/genographic/overview.html

Atlas of the human journey

https://www3.nationalgeographic.com/genographic/atlas.html

Your genetic journey

https://www3.nationalgeographic.com/genographic/journey.html

Educational Resources

Geography Action

http://www.ngsednet.org/commun.....unity_id=7

Earth Current News Digest

http://www.ngsednet.org/news/sample.cfm

Teaching Resources

http://www.ngsednet.org/commun.....ity_id=278

Genigraphic news

https://www3.nationalgeographic.com/genographic/resources.html
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Mon Feb 19, 2007 9:45 am    Post subject: Storing Digital Data in Living Organisms Reply with quote

Storing Digital Data in Living Organisms
Biotechnology Progress
19 February 2007

DNA, perhaps the oldest data storage medium, could become the newest as scientists report progress toward using DNA to store text, images, music and other digital data inside the genomes of living organisms. In a report scheduled for the April 9 issue of ACS' Biotechnology Progress, a bi-monthly journal, Masaru Tomita and colleagues in Japan point out that DNA has been attracting attention as perhaps the ultimate in permanent data storage.

Data encoded in an organism's DNA, and inherited by each new generation, could be safely archived for hundreds of thousands of years, the researchers state. In contrast, CD-ROMs, flash memory and hard disk drives can easily fall victim to accidents or natural disasters.

In their report, the researchers describe a method for copying and pasting data, encoded as artificial DNA, into the genome of Bacillus subtilis, (B. subtilis) a common soil bacterium, "thus acquiring versatile data storage and the robustness of data inheritance." The researchers demonstrated the method by using a strain of B. subtilis to store the message: "E=MC2 1905!" — Albert Einstein's famous 1905 energy-mass equivalence equation.

"We suggest that this simple, flexible and robust method offers a practical solution to data storage and retrieval challenges in combination with other, previously published techniques," the report states.

ARTICLE #1 FOR IMMEDIATE RELEASE
"Alignment-Based Approach for Durable Data Storage into Living Organisms"

DOWNLOAD PDF
http://pubs.acs.org/cgi-bin/sa.....60261y.pdf

DOWNLOAD HTML
http://pubs.acs.org/cgi-bin/sa.....0261y.html
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Sat Mar 10, 2007 8:07 am    Post subject: Study: Genes Make Women Cranky Reply with quote

Study: Genes Make Women Cranky

By Jeanna Bryner
LiveScience Staff Writer
posted: 09 March 2007
11:57 am ET

Thanks for the lousy temper, Mom and Dad.

Genetics could explain why some women are more ill-tempered than others.

A new University of Pittsburgh study finds genetic variations that deal with the body's mood management chemistry are linked with anger, aggression and hostility in women.

For the full article:

http://www.livescience.com/hum.....etics.html
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Sun Mar 11, 2007 7:45 am    Post subject: New Technique Stores Data in Bacteria Reply with quote

New Technique Stores Data in Bacteria

By Bill Christensen

posted: 10 March 2007
09:19 am ET

Artificial DNA with encoded information can be added to the genome of common bacteria, thus preserving the data. The technique was developed at Keio University Institute for Advanced Biosciences and Keio University Shonan Fujisawa Campus. If you think those USB flash memory "thumbdrives" are small, check this data storage out.

According to researchers, up to 100 bits of data can be attached to each organism. Scientists successfully encoded and attached the phrase "e=mc2 1905" to the DNA of bacillus subtilis, a common soil bacteria.

For the full article:

http://www.livescience.com/sci.....orage.html
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Wed May 09, 2007 11:39 am    Post subject: DNA repair proteins monitored at double-strand break Reply with quote

St. Jude Children's Research Hospital
9 May 2007

DNA repair proteins monitored at double-strand break

St. Jude researchers have tracked the movement of the cell's DNA repair kit proteins as they interact with each other and gather at the site of damage
Investigators at St. Jude Children's Research Hospital had a molecule’s eye view of the human cell’s DNA repair kit as it assembled on a double-strand break to link together the broken ends. Double-strand breaks are ruptures that cut completely across the twisted, ladder-like structure of DNA, breaking it into two pieces.

Using a technique developed specifically for this project, the St. Jude researchers could determine when repair proteins arrived at or around the DNA break and evaluate its repair—even when particular proteins shifted away from the break to make room for others. A report on this work appears in the May 7 online issue of "Nature Cell Biology."

The findings are important because disruption of the precise movement of these repair proteins can cause mutations, cell death or cancer, and the ability to track the process so closely will give researchers critical insights into what can go wrong with DNA repair. This could lead to novel ways to make cancer cells more sensitive to therapy by blocking their ability to repair double-stranded breaks caused by chemotherapy or radiation. It could also suggest new strategies for enhancing repair of double-stranded DNA caused by radiation, natural oxidants in food or the body and other toxins that can cause disease and aging.

"Prior to this work, there was no practical and efficient way to find and study the DNA repair proteins that organize themselves on and around a double-strand break in human cells," said Michael Kastan, M.D., Ph.D., St. Jude Cancer Center director. "Our approach solved that problem and allowed us to document the cell’s response to double-strand DNA breaks over time. The technique provides significantly more information about the proteins that repair DNA than is possible using the standard microscope-based approach previously used for such work." Kastan is the paper’s senior author.

A deficiency in two of these repair proteins, ATM and NBS1, leads to defects in double-strand break repair by disrupting the signaling processes triggered by the break. "A lack of functioning ATM causes ataxia-teleangiectasia, a disease that causes a variety of debilitating problems, such as neurodegeneration, cancer and sensitivity to irradiation leading to double-strand breaks that are not repaired," Kastan said. "And a lack of NBS1 causes Nijmegen breakage syndrome, another disease that leaves its victims at high risk for cancer and higher sensitivity to DNA-damaging radiation. So this work has important medical implications for these and other diseases linked to disruption of double-strand break repair."

The assay, developed by Elijahu Berkovich, Ph.D., in Kastan’s laboratory, demonstrates how key repair proteins, such as ATM, NBS1, XRCC4 and gamma-H2AX, interact to coordinate repair of double-strand breaks. For example, the investigators showed that NBS1 recruits ATM to the break; and that ATM and NBS1 cooperate to disrupt nucleosomes—the compact packages formed when strands of DNA wind around proteins, called histones, like thread around a spool. Disruption of the nucleosome at the site of a double-strand break allows the DNA to unravel and expose the area to repair proteins; the loss of functioning ATM and NBS1 blocks this important process. The team also showed that both NBS1 and ATM are needed to ensure that the repair factor, XRCC4, arrives at the double-strand break to help repair the damage.

In addition, the investigators showed that ATM initially binds to DNA both at the site of the break as well as on each side of it. However, XRCC4 later takes the place of ATM molecules at the break while the ATM molecules on either side of the break stay in place. The researchers suggested that ATM had been displaced or moved so that the repair proteins could gain access to the damaged DNA site.

The findings also suggested that before ATM can move to the double-strand break, it must first become activated so it can trigger a critical series of signals linked to DNA repair. Inactive ATM exists as a pair of these molecules linked together. Kastan previously reported in the journal Nature how the inactive ATM molecules separate from each other in response to a double-strand break (http://www.stjude.org/media/0,2561,453_5484_3126,00.html).

To control when and where the double-strand breaks occurred during the study, the researchers used an enzyme called I-PpoI, which naturally seeks certain DNA areas to cut. The investigators modified I-PpoI so that they could better control when the enzyme moves into the nucleus and cleaves the DNA. The team then used a biochemical technique called chromatin immunoprecipitation to collect and identify repair proteins and show where each one bound to the DNA.

###
The other author of this article is Raymond Monnat, M.D. (University of Washington).

This work was supported in part by the National Institutes of Health and ALSAC.

St. Jude Children's Research Hospital

St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization. For more information, please visit http://www.stjude.org
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Mon Jun 04, 2007 10:46 am    Post subject: Sleeping Beauty "jumping gene" shows promise for s Reply with quote

Sleeping Beauty "jumping gene" shows promise for sickle cell gene therapy
Biochemistry
4 June 2007

The Sleeping Beauty tranposon (SB-Tn) system, a gene therapy technology that avoids the pitfalls of transferring genes with viruses, shows promise in laboratory experiments for correcting the gene defect responsible for sickle cell disease (SCD), scientists in Minnesota are reporting.

In the study, scheduled for the June 12 issue of ACS' Biochemistry, a weekly journal, Clifford J. Steer and colleagues note that viruses have gotten most attention as possible vectors, or delivery vehicles, for replacing defective genes with normal copies. In SCD, a mutation in the gene that encodes for beta globin results in abnormal hemoglobin that gives red blood cells a sickle shape. Concerns about potential risks and other problems with viral vectors, however, have become barriers to use of gene therapy.

Using laboratory cell cultures, the researchers showed that SB-Tn system could transfer normal beta globin genes into cells. The system, named for a fish gene reawakened by other researchers in 1997 after 15 million years of dormancy, fulfills essential requirements for gene therapy, the report states. Cells take up genes transferred with SB-Tn technology, the genes produce beta globin in stable fashion for long periods, and the genes are inherited and passed along as cells reproduce. Scientists term Sleeping Beauty as a transposon, or a "jumping gene" because it can jump from one location on a piece of DNA to another.

ARTICLE #1 FOR IMMEDIATE RELEASE "Erythroid-Specific Expression of beta-Globin by the Sleeping Beauty Transposon for Sickle Cell Disease"

DOWNLOAD PDF http://pubs.acs.org/cgi-bin/sa.....024484.pdf
DOWNLOAD HTML http://pubs.acs.org/cgi-bin/sa.....24484.html
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Sat Jun 23, 2007 7:25 am    Post subject: St. Jude study shows genes play an unexpected role in their Reply with quote

St. Jude Children's Research Hospital
22 June 2007

St. Jude study shows genes play an unexpected role in their own activation

Researchers show that genes activated by the transcription factor CREB dictate which helper molecules it uses, a finding that may link CREB to responses such as learning, memory and glucose production in the liver
Investigators at St. Jude Children's Research Hospital have discovered how a single molecular “on switch” triggers gene activity that might cause effects ranging from learning and memory capabilities to glucose production in the liver.

The “on switch,” a protein called CREB, is a transcription factor—a molecule that binds to a section of DNA near a gene and triggers that gene to make the specific protein for which it codes. CREB activates genes in response to a molecule called cAMP, which acts as a messenger for a variety of stimuli including hormones and nerve-signaling molecules called neurotransmitters.

The St. Jude team showed that each gene that responds to CREB chooses which co-factors, or helper molecules, CREB uses to activate that gene. This finding adds an important piece to the puzzle of how cells use CREB to activate specific genes in response to cAMP signals.

It also suggests that the current model scientists use to explain how CREB works is too simple, said Paul Brindle, Ph.D., associate member of the Department of Biochemistry at St. Jude. Brindle is senior author of a report on this work that appears in the June 20 issue of “The EMBO Journal.”

“CREB is like a plumber who turns on the water flow in a pipe system by using a certain tool,” Brindle said. “What we discovered is that the CREB ‘plumber’ requires different tools to turn on different genes; and that each gene determines which set of co-factor tools from CREB’s toolbox it will respond to.”

In order to activate a gene, CREB must first get “tagged” by a molecule called phosphate. CREB then recruits a co-factor called CBP/p300 to the gene by binding to this protein at a site called KIX. Previously, scientists thought that a particular transcription factor uses the same co-factors to activate all its target genes.

The new findings showed that phosphate-tagged CREB binding to CBP/p300 at KIX does not account for most gene activation controlled by the cAMP messenger molecule. Instead, the binding of CREB to KIX is necessary for only part of the activation of certain target genes; those genes became activated even when KIX was disabled in CBP/p300. Further studies suggested that this KIX-independent mechanism can act on the same gene as the KIX-dependent mechanism; and that each mechanism may or may not contribute equally to activating a specific gene. The team also found evidence that other proteins can act as back-up co-factors for CBP/p300.

“This more complex view of how CREB works may help us understand how this single transcription factor can stimulate many different genes, depending on which tissues are using it and which signaling molecule caused cAMP to put CREB to work,” Brindle said. “It is another clue to how CREB might activate the genes for enzymes that make glucose in the liver, while activating different genes in the brain that are key to learning and forming memories.”

A long-term implication of this work is that one day it might be possible to manipulate CREB’s co-factors to treat disease. “A drug that blocked the specific co-factors CREB needs in the liver to trigger activity of genes that make glucose could reduce blood levels of this sugar in people with diabetes,” Brindle said. “But at the same time, CREB could continue its other jobs without interruption.”


###
Other authors of the study include Wu Xu, Lawryn Kasper, Stephanie Lerach and Trushar Jeevan (St. Jude).

This work was supported in part by the National Institutes of Health, a Cancer Center (CORE) support grant and ALSAC.

St. Jude Children's Research Hospital

St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization. For more information, please visit www.stjude.org
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Wed Jun 27, 2007 12:18 pm    Post subject: Scientists Discover Role of Enzyme in DNA Repair Reply with quote

Scientists Discover Role of Enzyme in DNA Repair
NIH
27 June 2007

Scientists from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Cancer Institute (NCI), and Integrative Bioinformatics Inc. have made an important discovery about the role of an enzyme called ataxia telangiectasia mutated protein (ATM) in the body’s ability to repair damaged DNA. NIAMS and NCI are part of the National Institutes of Health (NIH).

When DNA within a cell is damaged, the cell’s protective mechanism must do one of two things: repair the defect or “commit suicide,” says Rafael Casellas, Ph.D., an investigator in NIAMS’ Molecular Immunology and Inflammation Branch and leading author of a new paper describing the discovery. But the way in which the cell performs these protective functions has been largely a mystery, says Casellas, whose research is beginning to unravel this mystery.

Casellas’ research focuses largely on certain genes that are deliberately broken and repaired as part of the immune response. Through a tightly controlled process of breaking and rejoining DNA segments, immune system cells called B lymphocytes are able to produce tens of millions of different types of antibodies to fight almost limitless types of invaders. This process of genetic recombination requires the activity of repair enzymes, which must be able to recognize and repair breaks in tightly wrapped and inaccessible DNA. During immunoglobulin gene recombination, DNA is rendered accessible by the process of transcription, which unzips double-stranded DNA as part of the conversion of genetic information into functional proteins.

While transcription ensures accessibility to DNA lesions, Casellas wondered how it was possible for repair enzymes to do their job if transcription continued once DNA had been damaged. “Imagine a piece of DNA as a zipper,” he says. “The head of the zipper (the transcription complex) will repeatedly go through the two interlocked sides, coming to the broken part, and eventually falling off. One could imagine that this unzipping activity might interfere with the mechanism that is trying to repair the damaged DNA.”

Casellas hypothesized that once DNA lesions were generated, a regulatory activity would shut down transcription until repair enzymes corrected the damage. But because B lymphocyte cells are relatively scarce, Casellas and his colleagues chose to focus their investigation on a more abundant family of genes, known as ribosomal genes, as a substitute. They attached a green fluorescent protein to Polymerase I, a key component in the machinery that transcribes these genes, and were able to visualize the activity of this enzyme using microscopy. They then used a particular laser attached to the microscope to introduce DNA breaks at sites where the polymerase was active. This microscopy approach was developed by NCI’s Michael Kruhlak, Ph.D., first author in the report. Using the ProcessDB software developed by Integrative Bioinformatics Inc, Robert Phair, Ph.D. developed a computer model that allowed the authors to test their hypothesis and show that while transcription continued in the cells with uninjured DNA, it came to a halt within 5 minutes at sites where the DNA had been damaged.

While it was possible that the DNA lesions themselves physically interfered with transcription, the authors hypothesized that repair enzymes recruited by the damage could shut down the transcription machinery polymerase. To test this hypothesis, they repeated the experiment in cells that were deficient in a variety of repair proteins. Most deficiencies did not appear to affect the arrest; however, in cells that were missing one of three repair proteins factors — ATM, Nbs1 or MDC1 — transcription continued even after damage was induced.

“What these results told us was that these proteins were responsible for shutting down the transcription machinery near sites of DNA damage. This activity perhaps ensures repair in an undisturbed environment. If this is indeed the case, one could suspect that in the absence of these factors, repair is compromised, leading to genetic aberrations,” Casellas says. Indeed, scientists already know that people deficient in ATM develop such genetic abnormalities, cell transformation and tumor development. Although it’s too soon to say whether these laboratory discoveries will translate into clinical use, Casellas is enthused about the work. “With this new technology we can visualize for the first time the interplay between complex mechanisms such as DNA repair and gene transcription, not in a test tube, but in living cells and in real time. This approach will help us unravel the inner molecular pathways of our cells in health and disease, such as cancer.”

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services’ National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Tue Jul 03, 2007 9:40 am    Post subject: Cornell researchers determine how an enzyme plays a key role Reply with quote

July 2, 2007
Cornell researchers determine how an enzyme plays a key role in gene copying
By Krishna Ramanujan

Cornell researchers have answered a fundamental question about how two strands of DNA, known as a double helix, separate to start a process called replication, in which genes copy themselves.


The research, published in the current issue of the journal Cell, examined the role of an enzyme called a helicase, which plays a major role in separating DNA strands so that replication of a single strand can occur.

Scientists have known that helicases bind to the area of a double helix where the two strands fork away from each other, like the free ends of two pieces of thread wound around each other. The forked area opens and closes very rapidly. But scientists have debated whether helicases actively separate the two strands at the fork or if they passively wait for the fork to widen on its own.

For the full article:

http://www.news.cornell.edu/st.....es.kr.html
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Thu Jul 12, 2007 2:01 pm    Post subject: Unraveling the physics of DNA's double helix Reply with quote

Duke University
12 July 2007

Unraveling the physics of DNA's double helix

DURHAM, N.C. -- Researchers at Duke University's Pratt School of Engineering have uncovered a missing link in scientists' understanding of the physical forces that give DNA its famous double helix shape.

"The stability of DNA is so fundamental to life that it's important to understand all factors," said Piotr Marszalek, a professor of mechanical engineering and materials sciences at Duke. "If you want to create accurate models of DNA to study its interaction with proteins or drugs, for example, you need to understand the basic physics of the molecule. For that, you need solid measurements of the forces that stabilize DNA."

In a study published online by Physical Review Letters on July 5, Marszalek's team reports the first direct measurements of the forces within single strands of DNA that wind around each other in pairs to form the complete, double-stranded molecules. The work was supported by the National Science Foundation and the National Institutes of Health.

Each DNA strand includes a sugar and phosphate "backbone" attached to one of four bases, which encode genetic sequences. The strength of the interactions within individual strands comes largely from the chemical attraction between the stacked bases. But the integrity of double-stranded DNA depends on both the stacking forces between base units along the length of the double helix and on the pairing forces between complementary bases, which form the rungs of the twisted ladder.

Earlier studies have focused more attention on the chemical bonds between opposing bases, measuring their strength by "unzipping" the molecules' two strands, Marszalek said. Studies of intact DNA make it difficult for researchers to separate the stacking from the pairing forces.

To get around that problem in the new study, the Duke team used an atomic force microscope (AFM) to capture the "mechanical fingerprint" of the attraction between bases within DNA strands. The bonds within the molecules' sugar and phosphate backbones remained intact and therefore had only a minor influence on the force measurements, Marszalek said.

They tugged on individual strands that were tethered at one end to gold and measured the changes in force as they pulled. The AFM technique allows precise measurements of forces within individual molecules down to one pico-Newton--a trillionth of a Newton. For a sense of scale, the force of gravity on a two-liter bottle of soda is about 20 Newtons, Marszalek noted.

They captured the range of stacking forces by measuring two types of synthetic DNA strands: some made up only of the base thymine, which is known to have the weakest attraction between stacked units, and some made up only of the base adenine, known to have the strongest stacking forces. Because of those differences in chemical forces, the two types of single-stranded DNA take on different structures, Marszalek said. Single strands of adenine coil in a fairly regular fashion to form a helix of their own, while thymine chains take on a more random shape.

The pure adenine strands exhibited an even more complex form of elasticity than had been anticipated, the researchers reported. As they stretched the adenine chains with increasing force, the researchers noted two places—at 23 and 113 pico-Newtons--where their measurements leveled off.

"Those plateaus reflect the breaking and unfolding of the helix," Marszalek explained. With no bonds between bases to break, the thymine chains' showed little resistance to extension and no plateau.

Based on the known structure of the single stranded DNA molecules, they had expected to see only one such plateau as the stacking forces severed. Exactly what happens at the molecular level at each of the two plateaus will be the subject of continued investigation, he said.


###
Collaborators on the study include research associate Changhong Ke and graduate students Michael Humeniuk of Duke and Hanna S-Gracz of North Carolina State University.
Back to top
View user's profile Send private message Visit poster's website
adedios
SuperPoster


Joined: 06 Jul 2005
Posts: 5060
Location: Angel C. de Dios

PostPosted: Mon Aug 06, 2007 11:53 am    Post subject: In a Scientific First, Einstein Scientists Discover the Dyna Reply with quote

In a Scientific First, Einstein Scientists Discover the Dynamics of Transcription in Living Mammalian Cells

Albert Einstein College of Medicine of Yeshiva University

August 6, 2007 – (BRONX, NY) – Transcription — the transfer of DNA’s genetic information through the synthesis of complementary molecules of messenger RNA — forms the basis of all cellular activities. Yet little is known about the dynamics of the process — how efficient it is or how long it takes. Now, researchers at the Albert Einstein College of Medicine of Yeshiva University have measured the stages of transcription in real time. Their unexpected and surprising findings have fundamentally changed the way transcription is understood.

The researchers used pioneering microscopy techniques developed by Dr. Robert Singer, co-chair of anatomy & structural biology at Einstein and senior author of the study, which appears in the August issue of Nature Structural & Molecular Biology.

The study focused on RNA polymerase II--the enzyme responsible for transcription. During transcription, growing numbers of RNA polymerase II molecules assemble on DNA and then synthesize RNA by sequentially recruiting complementary RNA nucleotides.

To visualize the transcription process, the researchers used living mammalian cells, each of which contained 200 copies of an artificial gene that they had inserted into one of the cell’s chromosomes. Then, by attaching fluorescent tags to RNA polymerase II, they were able to closely monitor all three phases of the transcription process: binding of the enzyme molecules to DNA, initiation (when the enzyme links the first few RNA nucleotides together) and elongation (construction of the rest of the RNA molecule). As they observed the RNA polymerase II molecules attaching to DNA and making new RNA, they saw many cases where enzyme molecules attached — and then promptly fell off.

“One surprising finding was how inefficient the transcription process really is, particularly during its first two stages,” says Dr. Singer. “It turns out that only one percent of polymerases that bind to the gene actually remain on to help in synthesizing an RNA molecule. Transcription is probably inefficient for a reason. We’re not sure why, but it may be because all the factors needed for transcription have to come together at the right time and the right place, so there’s a lot of falling off and adding on of polymerases until everything is precisely coordinated.”

The researchers observed that the binding phase of transcription lasted six seconds and initiation lasted 54 seconds. By contrast, the final stage of transcription — elongation of the RNA molecule — took a lengthy 517 seconds (about eight minutes). The possible reason: The “lead” polymerase on the growing polymerase II enzyme sometimes “paused” for long periods, retarding transcription in the same way that a Sunday driver on a narrow road slows down all traffic behind him. But in the absence of pausing, elongation proceeded much faster — about 70 nucleotides synthesized per second — than has previously been reported.

These two phenomena — pausing and rapid RNA synthesis during elongation — may be crucial for regulating gene expression. “With this sort of mechanism, you could have everything at the ready in case you suddenly needed to rev up transcription,” says Dr. Singer. “Once the ‘paused’ polymerase starts up again, in a very short time you could synthesize a new batch of messenger RNA molecules that might suddenly be needed for making large amounts of a particular protein.”

The other Einstein researchers involved in the study were lead author, Xavier Darzacq (now at Laboratoire de Génétique Moléculaire, Centre National de la Recherche Scientifique, Paris), Yaron Shav-Tal (now at The Mina & Everard Goodman Facility of Life Sciences, Bar-Ilan University, Ramat Gan, Israel), Valeria de Turris and Shailesh M. Shenoy. Other collaborators were Yehuda Brody of Bar-Ilan University and Robert D. Phair of Integrative Bioinformatics, Inc., Los Altos, CA.
Back to top
View user's profile Send private message Visit poster's website
Display posts from previous:   
Post new topic   Reply to topic   printer-friendly view    USAP PAETE Forum Index -> Science Lessons Forum All times are GMT - 5 Hours
Goto page 1, 2  Next
Page 1 of 2

 
Jump to:  
You can post new topics in this forum
You can reply to topics in this forum
You cannot edit your posts in this forum
You cannot delete your posts in this forum
You cannot vote in polls in this forum


Powered by phpBB © 2001, 2005 phpBB Group