GENETICS : CREATING A CELL WITH SYNTHETIC DNA

Genetics: Creating a cell with synthetic DNA
United States - John Craig Venter, an American biologist shows for his research in genome sequencing, has managed his teams to create the first bacterium with a fully synthetic genome.

This bacterium has been made from the sequencing of the genome of the bacterium Mycoplasma mycoides. It's been 15 years since researchers at the J. Craig Venter Institute in Maryland, harnessed to the task. The cell contains more than one million base pairs, which is low compared to six billion contained in the human genome.

This is a great advance in the field of genetics, this research could lead to the design of artificial life forms that could help produce biofuels or pharmaceuticals. Important ethical issues arise, however, due to possible drifts around this technique.

Scanning electron micrographs of M. mycoides

More information can be found on the J. Craig Venter Institute web site at: http://www.jcvi.org/cms/research/projects/first-self-replicating-synthetic-bacterial-cell/

Journal Reference:
Daniel G. Gibson, John I. Glass, Carole Lartigue, Vladimir N. Noskov, Ray-Yuan Chuang, Mikkel A. Algire, Gwynedd A. Benders, Michael G. Montague, Li Ma, Monzia M. Moodie, Chuck Merryman, Sanjay Vashee, Radha Krishnakumar, Nacyra Assad-Garcia, Cynthia Andrews-Pfannkoch, Evgeniya A. Denisova, Lei Young, Zhi-Qing Qi, Thomas H. Segall-Shapiro, Christopher H. Calvey, Prashanth P. Parmar, Clyde A. Hutchison III, Hamilton O. Smith, and J. Craig Venter. Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome. Science, May 20, 2010 DOI: 10.1126 / science.1190719

DAILY SEX "HELPS IMPROVE SPERM QUALITY"

Daily Sex "Helps Improve Sperm Quality"

Australian study - Having sex daily increase sperm quality and thus assist men who have fertility problems.

The study was conducted on 118 Australians whose semen showed alterations, the researchers found that daily ejaculation for a week increased significantly reduce the number of DNA damage sperm of patients.

Dr David Greening and colleagues at the private clinic Sydney IVF (Australia), specializes in fertility problems, participants were asked to have sex every day for a week. After seven days, doctors have observed in 81% of subjects a decrease of 12% of the amount of damaged sperm. Sperm quality can also be improved if men do not smoke, do not abuse alcohol, do exercise and ingest more antioxidants.

Although the sperm count has dropped to 180 million per ml to 70 million per ml, men were still in the "range of fertility."

Since he led the study, Dr Greening said now recommend to all couples seeking advice to improve their fertility to begin to love more. One suggestion that seems to contradict the older men but delight the youngest, said the doctor.

Sex frequent help to improve sperm quality by preventing it from staying too long in the body. The sperm DNA was indeed more likely to be damaged when staying long in the body. Also heat can also make sperm less mobile.

Some experts welcomed the study but added that it does not prove that sex daily allows men with fertility problems to have a better chance of producing babies. Dr Greening and colleagues are still analyzing the results of the study to determine how many companions of participants became pregnant.

If confirmed, the discovery could have implications for in vitro fertilization (IVF) as was previously recommended for couples to abstain for two days just to increase sperm count.

"Studying the DNA of sperm is only part of the puzzle" said his side Bill Ledger, professor of obstetrics and gynecology at the University of Sheffield, Great Britain, who has not participated in the study.

"This may improve pregnancy rates, but we still need to study further" Mr. Ledger also believes that apply to couples with fertility problems to have greater love could harm their relationship.

"This could add to the anxiety and do more harm than good." Couples should not feel obliged to change their sexual life to have a baby, he said.
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This work was presented Tuesday, June 30, 2009 in Amsterdam at the Congress of the European Society of Human Reproduction and Embryology. (Website: http://www.eshre.com)
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Sources: BBC News, AP

A VERY PROMISING NEW DRUG AGAINST CANCER

A Very Promising New Drug Against Cancer

British researchers (from The Institute of Cancer Research) announce that they have obtained through a new drug against certain cancers, genetic, very promising results in preliminary clinical trials. The results were published in the medical journal The New England Journal of Medicine dated June 24, 2009 (Reference below).

A drug that targets cancer cells and leave normal cells intact
This new drug Olaparib was given to patients with advanced forms of cancer (breast, ovarian or prostate) inherited a mutation in the genes BRCA1 and BRCA2 (this genes were thought to be responsible for about 5% of breast and ovarian cancers, and about 1-2% of early onset prostate cancers). The Olaparib blocks the action of enzymes called PARP [Poly(ADP-Ribose)polymerase] involved in the mechanisms reparatinon DNA. Thanks to this drug in more than half of patients, the tumor had either stabilized or decreased in size. These patients had not responded favorably to standard treatment against cancer. The study shows that patients remained in remission two years after receiving treatment.

The Olaparib target cancer cells but leave normal cells intact. This medication has also very few side effects and some patients have reported that treatment was more bearable than chemotherapy.

Dr Johann de Bono, a researcher of the Institute of Cancer Research who led the clinical trials Phase I with the assistance of AstraZeneca / KuDOS said that positive results should permit completion of ESSI greater extent .

"This drug has shown very impressive to reduce the size of tumors in patients. It gives patients who have already tried many conventional treatments for long periods of remission, free of any symptoms or side effects " said the researcher.

Synthetic Lethality
Olaparib is the first successful example of a new type of personalized medicine using the principle of "synthetic lethality" (synthetic lethality in English), the medicine works effectively with molecular defect of the patient. This treatment is based on experiments conducted in this institute have shown that some cancers had Achilles' heels: if drugs - as olaparib - are used to block an enzyme called PARP in the body, DNA the tumor cell is broken and the cell dies.

Cancers with BRCA1 or BRCA2 mutations were first discovered as being sensitive to inhibition of PARP but there are evidences which suggest that olaparib will be effective in other cancers with defects in machinery repair of DNA. This could apply to certain cancers of non-inherited breast or prostate cancers and up to half of the most common forms of ovarian cancer.

"It is a very important drug for the treatment of cancers associated with BRCA1 / 2. The next step is to test the drug on a more common form of cancer of the ovaries or breast or we hope that this drug will be equally effective." said Professor Stan Kaye who co-led the study.

Professor Alan Ashworth who now runs the charity Breakthrough Breast Cancer Research Center participates in the financing of this research is the source of the work of targeting mechanisms réapration DNA in cancer.

"We are extremely pleased that the work that we conducted in the laboratory are translated as quickly as benefits to patients. This concept is now tested in clinical trials deifferents worldwide." said the professor.

The mode of action of this drug
The concept behind this new approach is called "synthetic lethality". Normal cells have different ways of repairing damage to their DNA. In the case of BRCA tumors, a means of compensation is absent. Olaparib the drug blocks a different path involving the enzyme PARP, normal cells are not affected by this medication because they can use the BRCA genes. When the drug is used on the BRCA tumors, they have no means to repair their DNA when they die. Therefore, this drug is so effective at killing cancer cells and do not affect normal cells.
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Reference:
Article: Inhibition of Poly (ADP-Ribose) Polymerase in Tumors from BRCA Mutation Carriers
Authors: Peter C. Fong, David S. Boss, Timothy A. Yap, Andrew Tutt, Peijun Wu, Mergui-Marja Roelvink, Peter Mortimer, Helen Swaisland, Alan Lau, Mark J. O'Connor, Alan Ashworth, James Carmichael, Stan B. Kaye, Mr. Jan H. Schellens, and Johann S. Bono
Journal Publication:
DOI: 10.1056/NEJMoa0900212
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Source : BBC Health

THE NOBEL PRIZE IN CHEMISTRY 2009 : RIBOSOMES IN THE SPOTLIGHT

The Nobel Prize in Chemistry 2009 : Ribosomes In The Spotlight
The Nobel Prize in Chemistry has been awarded to two Americans and one Israeli for their work on ribosomes. This research promises advances in the treatment of diseases through the improvement of antibiotics.

The Nobel chemistry prize three researchers for their studies of ribosomes: Venkatraman Ramakrishnan (MRC Laboratory of Molecular Biology, Cambridge, United Kingdom), Thomas A. Steitz (Yale University, USA) and Ada E. Yonath (Weizmann Institute of Science, Israel).

These components of the cell, real manufacturing proteins via translation of DNA, are major targets for antibiotic action of many of them being to prevent bacterial ribosomes to function, said the academy Royal Swedish Society of Sciences.

Together, they conducted a three-dimensional mapping at the scale of the atom in this complex enzyme. Ribosomes, real biochemical plants, read the genetic code to produce proteins necessary for the establishment and functioning of organisms. Hemoglobin, hormone, enzyme digestion, consisting of cells, antibodies ... all that is synthesized by ribosomes. This is true for humans, but also for disease-causing bacteria.

In blocking the functioning of the ribosomes that antibiotics fight against bacteria. Better understanding is therefore better to fight against the disease.

The three distinguished scientists have used the X-ray crystallography to detail the atomic structure of ribosomes and develop models to explain their association with various antibiotics. These models are now used for the development of new drugs.

With the 10 million kronor (980,000 euros), the Nobel chemistry prize investment of all the teams of these three researchers, whose work is used since 2000 to develop new antibiotics.

Synthetic Biology: Genome Transferred Between Two Bacteria Via Yeast

One More Step Towards A Synthetic Genome - Artificial life
Scientists were able to transfer the genome of a type of bacteria in yeast, edit, and then successfully transplanted into a second type of bacteria. This research has helped to overcome any obstacles to create new micro-organisms that may one day be used to produce biofuels, clean up toxic sites, retaining the carbon or other applications. These works are being published in the latest issue of Science (reference below).

Carole Lartigue and colleagues had already found a way to transplant the genome of a bacterium, Mycoplasma mycoides, into another, Mycoplasma capricolum. They also realized that to transplant the genome of M. mycoides in yeast gave way to alter the genome of another way.

How can the bacteria host accepts foreign DNA?
To transplant the genome changed in a new bacterium, researchers were faced a problem similar to that of surgeons performing a transplant operation: how to make the recipient accepts the foreign element?
Many bacteria use systems of restriction enzymes to protect themselves against foreign DNA. They are equipped with enzymes called "restriction" can recognize short sequences of DNA and cut.

To protect their own DNA, the bacteria bind to specific positions on the genome of chemicals called methyl groups. Yeasts, however, do not methylate their genome in this way.

After transplanting the genome of M. mycoides in yeast and have eliminated a nonessential gene, which could have been done in the bacterium itself, Lartigue and colleagues were able to circumvent two-step restriction made by the host bacterium, M. capricolum. They were first inactivated enzyme restriction of M. capricolum and methyl groups added to the genome changed even in yeast. Then they were transferred in M. capricolum genome, which occurs after several cycles of division a new strain of the microbe donor, M. mycoides.
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Reference:
Article: Creating Strains from Bacterial Genomes that Have Been Engineered and Cloned in Yeast
Authors: Carole Lartigue, Sanjay Vashee, Mikkel A. Algire, Ray-Yuan Chuang, Gwynedd A. Benders, Li Ma, Vladimir N. Noskov, Evgeniya A. Denisova, Daniel G. Gibson, Nacyra Assad-Garcia, Nina Alperovich, David W. Thomas, Chuck Merryman, Clyde A. Hutchison, Hamilton O. Smith, J. Craig Venter, John I. Glass
DOI: 10.1126/science.1173759
Journal Publication: Science
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Source: EurekAlert

HUMAN STEM CELLS FREE OF FOREIGN DNA

Human Stem Cells Free Of Foreign DNA
U.S. researchers have developed a method to produce human induced pluripotent stem cells, or iPS cells, which contain no foreign, potentially harmful DNA. The report of this work are published in the latest issue of the journal Science.

Stem cells are induced pluripotent human adult cells that were "reprogrammed" into embryonic stem cells.

This result is important for the use of these cells in basic research in biology and is a key step in view of producing induced pluripotent stem cells used in medical therapy without the risk that elements inserted into their genome interfere with the development normal cell. When researchers in the early days reprogrammed adult and fetal cells so they become induced pluripotent stem cells, they used viruses to insert the processed key genes in the nucleus can trigger the reprogramming process.

Jungying Yu and his colleagues at the University of Wisconsin-Madison (USA) now describe an alternative to this approach. They added genes to circular DNA fragments called plasmids generally independent of cellular chromosomes. Then they introduced the plasmids into human foreskin cells by a process called nucleofection. The proteins expressed by genes carried by plasmids were then able to reprogram cells into iPS cells. Finally, the iPS cells began to lose their plasmid during cell division and researchers were then able to isolate which carried no more.

In their article, the authors state that other teams have recently reported methods with the same objective, but that their process is currently the only producing iPS completely devoid of human vectors and transgenic sequences.
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Article: Human Induced Pluripotent Stem Cells Free of Vector and Transgene Sequences
Authors: Junying Yu, Kejin Hu, Kim Smuga-Otto, Shulan Tian, Ron Stewart, Igor I. Slukvin, James A. Thomson
Journal Publication: Science
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Source: EurekAlert
Credit: UW-Madison

LIFE

Life
Life appeared on Earth there are 3.5 million years. Primitive organic molecules were transferred into organic molecules, with a favourable composition of atmospheric gases. They then evolved into cells, organism’s basic living world. Therefore, living beings have been born through protein synthesis, carried out by RNA enzymes, and multicellular organization, permitted by the system of duplication.

The life of a person, animal or plant, is punctuated by inevitable stages during its formation and its existence. It starts with fertilization, natural process made possible by the encounter of a male gamete and a female gamete. The embryo thus formed grows, and becomes a fetus as it grows. At birth, he takes his status of being alive and going through new phases: childhood, adolescence, adulthood, old age and death. Sociologists have also developed theories based on different life stages of an individual to describe his lifestyle and needs. Furthermore, the concept of life is very important in philosophy and in certain religious principles, so that its interruption by death remains a taboo in our society.

Biologically, life is defined by the presence in an individual function to its growth, motility, reproduction, but also metabolism, consumption and transformation of energy and a spontaneous response to external stimuli. The life support resides in cell division. There are indeed in a cell, the genetic material that encodes the different characteristics of a living being. It is carried by genes, arranged on chromosomes, consisting of DNA.

Actions that govern human life have been studied by scientists seeking to understand and reproduce the behaviour. Thus, the first artificial living beings were created in the 40s, and are in fact robots capable of performing mechanical actions. The robots first appeared shortly after and the concepts of artificial intelligence with them, since the best machines have programs that allow them to chain movements and react to certain environmental changes.

Moreover, researchers have identified the process of formation of life. They are now able to create beings perfectly viable, similar to natural individuals. Cloning techniques have been implemented. They are based on very sophisticated biological techniques, which use the genetic material of a cell, which can be modified to give birth to an individual with characteristics chosen. These processes are still exposed by ethics, since they constitute a challenge to the spontaneity of nature and the random creation of living beings.

DNA CONTORTIONIST

DNA Contortionist
Researchers have found a way that DNA strands are twisted to give different forms, which may one day be used to fabricate nanoscale systems to provide drugs to the body, train or study tissue samples of proteins. Their discovery offers the potential for nanotechnology to construct objects with continuous curvature.

Hendrik Dietz and his colleagues describe in the latest issue of Science (reference Article 1 below) how the nanoscale curved objects such as wheels, arches, hooks. They designed beams DNA helices arranged in a honeycomb. Some of these propellers have additional base pairs, while others have less, thus creating tensions across useful for assembling beams curved objects.

Using this method the researchers have managed to control the direction and degree of curvature, even going back to molecules with angles very closed. The authors were able to combine different elements curved in order to build complex shapes such as balls or sprockets.

Yan Liu and Hao Yan back on the job in a related Perspective article (reference section 2 below).
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References:
Article 1: Folding DNA into Twisted and Curved Nanoscale Shapes
Authors: Hendrik Dietz, Shawn M. Douglas, William M. Shih
Journal Publication: Science

Article 2: Designer Curvature
Authors: Y. Liu and H. Yan
Journal Publication: Science