Tuesday, October 30, 2007

One Step Closer To Elusive Cancer Vaccine

When cells become cancerous, the sugars on their surfaces undergo distinct changes that set them apart from healthy cells. For decades, scientists have tried to exploit these differences by training the immune system to attack cancerous cells before they can spread and ravage the body.

Now, researchers at the University of Georgia Cancer Center have synthesized a carbohydrate-based vaccine that – in mice – has successfully triggered a strong immune response to cancer cells. The finding, published in the October issue of the journal Nature Chemical Biology, brings the scientists one step closer to a much-sought-after “cancer vaccine.”

“In mice we can illicit very strong antibody responses and we have shown that the antibody responses are functional – that they can kill cancer cells,” said lead author Geert-Jan Boons, Franklin professor of chemistry.

Vaccines are currently used to prevent diseases by priming the immune system to recognize and attack a virus or bacteria. The vaccine that Boons and his team have developed, on the other hand, is a therapeutic vaccine that trains the body’s immune system to fight an existing disease.

The discovery in the 1970s of unique sugars on cancer cells set scientists in search of a way to get the immune system to recognize and attack cells that express these cancer-associated sugars. Until now, however, the results have been less than spectacular.

Cancer cells originate in the body, and the immune system leaves them alone because it distinguishes between the body’s own cells and foreign invaders such as viruses and bacteria.

Boons explained that early cancer vaccines were created by linking the tumor-associated carbohydrate with a foreign protein. The immune system, perhaps not surprisingly, attacked the protein and the linker molecules, but generally left the carbohydrate alone.

“We needed to come up with a vaccine that does not give our immune system a chance to go after anything else but the tumor-associated carbohydrate,” Boons said. “In other words, there should no junk that can induce an immune response to something other than the tumor-associated carbohydrate.”

Rather than using naturally derived and purified proteins and linkers, Boons and his team created a vaccine synthetically from scratch by stacking molecules together and arranging them in the appropriate configuration. In 2005, they created a fully synthetic vaccine that stimulated an immune response to the tumor-associated carbohydrate alone. The vaccine stimulated only low antibody levels, however, so the researchers began optimizing the components of the vaccine to illicit a stronger immune response.

Their optimized vaccine includes a tumor-associated carbohydrate that triggers the immune system’s B cells, a part of a protein that triggers the immune system’s T cells and a linker molecule that stimulates the production of generalized immune components known as cytokines.

The results of their three-pronged approach were astounding, particularly with respect to a critical component of the immune system known as IgG.

“When we tested our best vaccine we got really, really fabulous antibody levels that have never been seen before,” Boons said. “The levels of IgG antibody production were 100 times better than with conventional approaches.”

The vaccine has been successful in creating an antibody response that can kill cultured epithelial cells – those commonly involved in most solid tumors, such as breast and colorectal cancer – derived from mice and in stimulating an immune response in healthy mice. The researchers are currently testing the vaccine in mice with cancer, and Boons hopes to start phase I clinical trials in humans within a year.

Despite his enthusiasm for his work, Boons cautions that it’s too early to predict how the vaccine will perform in humans.

“There’s a very big step going from mice to humans,” he said. “Other cancer vaccines have worked in mice but not in humans.”

In addition to testing the new vaccine, Boon’s team is exploring the specific components of the immune response as they relate to cancer, determining the exact cytokines and antibodies that are most effective against cancer cells.

“We’re looking at which molecules are being upregulated at each level of immune response,” Boons said. “That gives us a road map to further optimize each component of the vaccine.”

The research is supported by the National Cancer Institute.

Source


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Monday, October 22, 2007

What is the Chiari Malformation?

The Chiari I Malformation is considered a congenital malformation, although there have been some reported cases of an acquired form. It is characterized by a small or misshapen posterior fossa (the compartment in the back of the skull), a reduction in cerebrospinal fluid pathways and a protrusion of the cerebellar tonsils through the bottom of the skull (foramen magnum) into the spinal canal. The tonsils would normally be round but often become elongated as they protrude down the spinal canal. Diagnosis can be difficult because not all patients will have the classical sign of deeply herniated tonsils.

Since the advent of MRI, the incidence of the Chiari I Malformation has risen
dramatically. MRI is safe and painless and currently the most reliable means available for diagnosing Chiari Malformations. Chiari Malformations are also known as herniation of the cerebellar tonsils, cerebellar ectopia, hindbrain herniation and Arnold-Chiari malformations.
A German pathologist, Professor Hans Chiari, first described abnormalities of the brain at the junction of the skull with the spine in the 1890's. He categorized them in order of severity, types I, II, III, and IV.

The Chiari type II Malformation is usually found in children with spina bifida or myelomeningocele. Not only is part of cerebellum unusually low and lying below the bottom of the skull, but the brain stem can be malformed in several ways. Types III and IV represent gross herniations of the cerebellum and are very rare.

What are the symptoms?
Many people with the Chiari I Malformation experience no symptoms. When symptoms are present, they usually do not appear until adolescence or early adulthood, but can occasionally be seen in young children. The majority of patients complain of severe head and neck pain. Headaches are often accentuated by coughing, sneezing or straining. Patients may complain of dizziness, vertigo, disequilibrium, muscle weakness or balance problems. Often fine motor skills and hand coordination will be affected.

Vision problems can also occur. Some patients experience blurred or double vision, difficulty in tracking objects or a hypersensitivity to bright lights. Physical examination may reveal nystagmus (involuntary eye movements). Other symptoms include tinnitus (buzzing or ringing in the ear), hearing loss or vocal cord paralysis. Patients may have difficulty swallowing, frequent gagging and choking and, in some cases, sleep apnea may be present.

The Chiari I Malformations may also be associated with other disorders such as hydrocephalus (build up of fluid in the ventricles of the brain) or Syringomyelia. Syringomyelia is a disorder in which cerebrospinal fluid enters the spinal cord, forming a cavity known as a syrinx. It is recommended that patients diagnosed with a Chiari Malformation have the entire spine imaged to rule out the presence of a syrinx, since it may be a consideration in treatment and prognosis.

Is there a treatment?
Surgical procedures to enlarge the posterior fossa are considered a treatment option for patients with the Chiari I Malformation. Techniques are quite diversified amongst neurosurgeons, and patient responses vary greatly. A successful surgery will alleviate pressure on the neural elements and may result in an improvement of symptoms.

The decision to treat a Chiari Malformation surgically requires careful consultation between patient and physician. Factors to be considered are the patient's current neurological condition and progression of symptoms over a period of time.

Is this condition hereditary?
Research into the risk of inheritance for the Chiari I Malformation is still in its early stages. In some families, more than one member has been documented to have the Chiari I Malformation. Familial recurrences are suggestive of a possible genetic component of the condition, but unfortunately there is no conclusive answer to the question of inheritance at this time. It is currently recommended that only those relatives experiencing symptoms commonly associated with the Chiari I Malformation need undergo investigational procedures.


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Codon Devices Awarded $1.5 Million Grant by National Institute of Standards and Technology

Codon Devices, Inc., the Constructive Biology Company™, today announced that it has been awarded a $1.5 million grant from the U.S. Commerce Department’s National Institute of Standards and Technology (NIST).

With the support of the grant, Codon Devices will develop an integrated microfluidics platform to significantly reduce the cost and complexity of building complex DNA fragments. This platform will advance the state of the art in gene synthesis to improve the utility of synthetic biology approaches for biotechnology research.

"We are thrilled that NIST has recognized Codon Devices with this ATP award,” said Brian M. Baynes, Founder and President of Codon Devices. “Funding from this initiative will enable us to develop a new generation of rapid, automated systems for construction of longer, more complex DNA sequences. By integrating this technology with our BioFAB™ Production Platform, we will make these new tools available to our customers and partners and accelerate critical applications such as drug discovery and development of renewable energy systems.”

The NIST award was granted under the Agency’s Advanced Technology Program (ATP). Awarded projects were selected for funding by a competitive, peer-reviewed process that evaluated the scientific and technical merit of each proposal and the potential for broad-based benefits to the nation. NIST promotes U.S. innovation and industrial competitiveness by advancing measurement science, standards and technology in ways that enhance economic security and improve our quality of life.

About Codon Devices

Codon Devices, Inc., based in Cambridge, MA, is a privately-held biotechnology company focused on enabling commercial applications of synthetic biology. Codon Devices' proprietary synthesis and design technologies improve the productivity of its industrial, pharmaceutical and academic customers in a paradigm shift to what the Company calls Constructive Biology™. The Company's focus is on developing and delivering high-value products and design services in a variety of application areas, including engineered gene libraries, engineered cells that produce novel pharmaceuticals, improved vaccines, agricultural products, and biorefineries for the production of industrial chemicals and energy. Codon Devices' BioFAB™ Production Platform uses sophisticated informatics, robotics and sequencing technologies to accurately synthesize genetic codes orders of magnitude more rapidly and cost-effectively than other currently available technology. More information about Codon Devices is available at www.codondevices.com.


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Friday, October 19, 2007

Guarding against the misuse of synthetic genomics

Synthetic genomics research involves using chemically created pieces of DNA known as oligonucleotides to design and assemble parts of, or complete chromosomes and genes.

In theory, these can then be used to generate new 'lifeforms' that can produce new biological drugs or biologically produced green fuels, which are impractical to engineer using more conventional biotechnology approaches.

However, as with any new technology that has the ability to be used for good comes the possibility that it can be subverted for evil means such as bioterrorism.

The 66 page report, entitled "Synthetic Genomics: Options for Governance", is a result of a 20 month examination of the field and has highlighted areas three key areas for policy intervention to ensure that this promising technology cannot be misused.

The need for such a review has accelerated over the last 5 years or so as the speed at which genetic constructs can be developed has increased dramatically, as has the number of companies that have the ability to develop them -this in turn has led to prices dropping rapidly.

"Designing ways to impede malicious uses of the technology while at the same time not impeding, or even promoting beneficial ones, poses a number of policy challenges for all who wish to use or benefit from synthetic genomics" said Michele Garfinkel, policy analyst at the J Craig Venter Institute and lead author of the report.

The first area involves those companies that supply synthetic DNA, oligonucleotides, genes or genomes and how they can ensure that they can trust that the researchers they are shipping their goods to are 'legitimate' users and not potential terrorists. In addition, the report recommends that these firms should collect customer details and information about their orders.

Some companies are already going beyond these recommendations of their own volition.

According to Dr Michael Dyson, Codon Devices' European managing director; every sequence they are asked to synthesise is checked against a database of high-risk sequences that could be used for nefarious means.

If a sequence is flagged up then the manufacture is stopped and discussions with the purchaser are initiated to find out exactly what the sequence is and what it will be used for.

The second area covers recommendations to control and/or monitor the use of DNA synthesisers, such that owners would have to be licensed and register the instruments as well as needing a license to buy reagents and services.

The third area involves the compilation of a manual for "biosafety in synthetic biology laboratories" as well establishing a recognised clearing house for best practice.

The review also calls for the broadening of the US Institutional Biosafety Committee's (IBC) review responsibilities to consider risky experiments as well as enhancing the enforcement of compliance with US National Institutes of Health (NIH) biosafety guidelines.

While these suggestions may appear to some to be somewhat draconian and could hinder honest research into beneficial systems, the committee was keen to stress that all the recommendations were designed to impose the minimum burden on researchers, industry and government.


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Wednesday, October 10, 2007

This 'new life form' is just reassembled car parts

Great scientific advances - unlike these latest claims - open up whole new areas of knowledge, says Nick Gay

Dr Nick Gay
Wednesday October 10, 2007
The Guardian

The Guardian's front-page story reported Craig Venter's claims that he is "poised to announce the creation of the first new artificial life form on Earth" (I am creating artificial life, declares US gene pioneer, October 6). On the face of it this seems to be a spectacular advance. Unfortunately the truth is rather different.

To provide an analogy, it is as if he had selected a set of car parts, assembled them into a car and then claimed to have invented the car. It will not "herald a giant leap forward in the development of designer genomes". It is merely the crudest and most facile kind of reductionism, an experimental approach that provides no insight whatever into the fundamental nature of cellular processes.

In fact the ability to carry out such a project relies on the work of thousands of scientists who have studied the molecular biology of the cell during the last 50 years and defined the function of basic cellular processes such as the replication of DNA and the conversion of RNA into proteins, and developed key methods such as the chemical synthesis of nucleic acids. Simply reassembling these cellular components into an "artificial" organism will not further our understanding of these life processes.

Your article also claims that his work "could unlock the door to new energy sources and techniques to combat global warming". It is certainly possible that the plant enzyme responsible for removing carbon dioxide from the atmosphere could be engineered to be more efficient, but this would not need Venter's artificial life - it could be achieved easily with the existing methods of genetic manipulation.

In another article on the same day you referred to the sequencing of Venter's own genome (Gene genie, October 6). This is an obvious, if somewhat egocentric, thing to do and a number of other single-genome sequences are in progress. But the idea alluded to, that you could predict the date of your death using this information, is absurd. Most human diseases are caused by the action of many genes in a complex interaction with the environment. The origin and progression of these polygenic diseases is poorly understood, and sequence information alone will not provide the answers.

It should also be noted that the ability to sequence whole genomes has little to do with Venter. It derives from the work of Fred Sanger at Cambridge in the 1970s. Venter, remember, was the man who tried to patent the human genome sequence and then exploit it for profit.

It is a feature of great scientific advances that they open up whole new areas of knowledge to view. This is well illustrated by the award this week of the Nobel prize for medicine to Martin Evans, Mario Capecchi and Oliver Smithies for the discovery and exploitation of stem cells.

These findings have led to a revolution in our understanding of cell and developmental biology and offer the prospect of new therapies for human diseases such as Alzheimer's. Venter's "artificial life" is not in the same league.

· Dr Nick Gay is a reader in cell signalling and development at the department of biochemistry, University of Cambridge


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Codon Devices expands gene scaffolding reach

Constructive Biology expert, Codon Devices, has opened a European subsidiary in the UK to support the rapid growth of the advanced gene synthesis and protein engineering markets.

The new subsidiary, Codon Devices UK, will focus in offering service and support help to its expanding synthetic biology customer base in Europe, Scandinavia and Israel.

The use of synthetic biology methods to construct engineered cell lines that increase the efficiency of biological drug and vaccine formation or speed-up the drug discovery process is ever increasing.

In addition, such systems can be used to generate enzymes that produce industrial chemicals or aid in the breakdown of plants for biofuel applications.

Traditionally, researchers have had to clone specific genes and splice them into an organism's DNA.

Codon Devices' fee-for-service offering allows researchers to specify a sequence that Codon will then synthesise and ship to the customer, enabling them to spend more time studying the effects of the sequences.

"There is a move away from cloning genes yourself in the laboratory as long as you can find a vendor such as Codon to supply you with gene constructs for expression libraries protein structure libraries," said Dr Michael Dyson, European Managing Director and head of Codon'd European subsidiary.

Such is the groundswell of demand that Dr Dyson estimates that the market will reach a size of around $2bn a year in the near future, compared with $40m a year before 2005.

This growth is helped by reduced costs associated with making these sequences enabled by high throughput parallel synthesis techniques that. Codon's facility can currently make up to 5 megabase pairs a month and is still scaling up production.

Historically, manufacturing of DNA was to stick together oligonucleotides but was only really useful in making oligomers up to 100 base pairs, and anything bigger was very difficult to QC.

Codon has developed a parallel synthesis platform dubbed BioFAB, which uses sophisticated informatics, robotics and sequencing technologies to accurately synthesize genetic codes.

The company claims that its BioFAB system can produce the gene constructs more rapidly and cost-effectively than other currently available technology

Indeed, last July, the company announced the successful construction and delivery of a sequence-verified, 35-kilobase genetic construct for Microbia's Precision Engineering business unit.

The construct was an 80 per cent synthetic gene cluster that codes for an optimised biosynthetic pathway used to produce an active pharmaceutical ingredient.

The company is also heavily involved in partnering companies to help them overcome especially challenging projects.

"It's very complex biology and what we do is a generation away from simply constructing oligomers using the Caruthers synthesis, we look at how to best construct the molecules, how you error check them and checking them for function," said Dr Dyson.

Indeed, the global demand for Codon's approach is such that the company has plans to expand operations in the Pacific Rim regions.

"Codon is investing heavily to address the global need for this technology and our expansion into Europe is being matched by an expansion into Japan and the Pacific Rim," said Dr Dyson.


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Gene Expression Profiling of Cuticular Proteins across the Moult Cycle of the Crab Portunus pelagicus

Background

Crustaceans represent an attractive model to study biomineralization and cuticle matrix formation as these events are precisely timed to occur at certain stages of the moult cycle. Moulting, the process by which crustaceans shed their exoskeleton, involves the partial breakdown of the old exoskeleton and the synthesis of a new cuticle. This cuticle is subdivided into layers some of which become calcified and some which remain uncalcified. The cuticle matrix consists of many different proteins which confer the physical properties, such as pliability, of the exoskeleton.

Results

We have used a custom cDNA microarray chip, developed for the blue swimmer crab Portunus pelagicus, to generate expression profiles of genes involved in exoskeletal formation across the moult cycle. Twenty-one distinct moult cycle related differentially expressed transcripts representing crustacean cuticular proteins were isolated. Thirteen contain copies of the cuticle_1 domain, previously isolated from calcified regions of the crustacean exoskeleton. Four transcripts contain a chitin_bind_4 domain (RR consensus sequence), associated with both the calcified and un-calcified cuticle of crustaceans. Four transcripts contain an unannotated domain (PfamB_109992) previously isolated from C. pagurus. Additionally cryptocyanin, a hemolymph protein, involved in cuticle synthesis and structural integrity, also displays differential expression related to the moult cycle. Moult stage-specific expression analysis of these transcripts revealed that differential gene expression occurs both among transcripts containing the same domain and among transcripts containing different domains.

Conclusions

The large variety of genes associated with cuticle formation, and their differential expression across the crustacean moult cycle, point to the complexity of the processes associated with cuticle formation and hardening which involve many components and require strict regulatory mechanisms. This study provides a molecular entry path into the investigation of the gene networks associated with cuticle formation.


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Monday, October 01, 2007

Grant winner scoffs at genius label

By Elise Kleeman Staff Writer

PASADENA - Paul Rothemund does not consider himself a genius.

"At Caltech and elsewhere, I am surrounded by real geniuses all the time, people much quicker than me in a variety of ways," said the tall, brown-haired Caltech scientist.

Some, it seems, would disagree.

Rothemund, 35, was one of 24 recipients of the prestigious MacArthur Fellowship, a $500,000 prize often known as the "genius grant."

The no-strings-attached award can be used by the recipients any way they please and is intended to "enable recipients to exercise their own creative instincts for the benefit of human society," according to the MacArthur Foundation.

When they call you, Rothemund said, "they say, `The only thing you have to do is cash the checks. We have no expectations of you, you don't need to report back what you're doing, you're never going to hear from us again. Bye."'

Among this year's other prize winners are a blues musician, a spider silk biologist, a medieval historian, two painters, an author of short stories and another Caltech scientist - Michael Elowitz, a 37-year-old molecular biologist.

Like all the other winners, Elowitz found out about the prize a week before the rest of the Advertisement world.

"I received a phone call, which, among other things, swore me to secrecy," he wrote by e-mail last week from Greece, where he was attending a conference. "The element of secrecy, however transient, really added to the fun. It was one of the best phone calls for me in recent memory."

Both Elowitz and Rothemund are in the forefront of a new interdisciplinary field that some call synthetic biology.

"There's a convergence between a number of fields - chemistry, biology and computer science, where people are thinking about how to create biological circuits or how to program biology," said Erik Winfree, the director of the lab in which Rothemund works and himself a 2000 MacArthur Fellow.

Elowitz's work involves studying chains of interactions between genes and proteins that allow cells to process information, make decisions and communicate.

"He does some of the most beautiful experiments I know of," Winfree said. "They're simultaneously aesthetically pleasing - you could put them on your wall - and scientifically elegant, rigorous."

(In fact, Elowitz does display some images from his experiments on the walls of his lab.)

He studies genetic pathways by linking different genes in bacteria to the production of a rainbow of fluorescent colors. By videotaping how the bacteria's colors change, he can watch as the microbes pass through the steps of the genetic circuit.

"You have something that sort of looks like Froot Loops, except it's growing organisms," said Winfree of the bacteria.

Winfree describes Elowitz as "a joy because he's an enthusiastic, funny guy" who is "so excited about the things he's doing."

Rothemund also works with genetic material, using a loop of virus DNA to create what he calls "DNA origami."

By adding smaller, synthetic strands of DNA that act as staples, he figured out how make the viral DNA fold itself into any shape he wants, each about one-one-thousandth the width of a human hair.

So far, those shapes have included smiley faces, maps of North America, and snowflake patterns. But his technique could one day be the basis for the construction of smaller and faster computer chips.

"It was an exciting development," said Ned Seeman, a New York University chemist who also uses DNA as tiny molecular building blocks. "A lot of the things that we're doing in my lab have been reoriented because of the things Paul did."

Unlike previous, less successful techniques for constructing with DNA, Rothemund's is surprisingly simple.

The virus DNA is easy to come by and the DNA staples can be made to order, Rothemund said.

"They come in a FedEx package, and you take the little tubes and dump them together, add a little saltwater, heat them up and cool them off," he said.

Then, voila - in a single drop of water are a hundred billion shapes.

One "enormous challenge," though, "is figuring out how to put them where you want them and get them in the right orientation," he said.

"I haven't even begun to think of what to do with the money, but one non-scientific fantasy involves tennis lessons," Elowitz wrote. "I plan to resist the temptation to take up an extreme sport."

Source : www.whittierdailynews.com


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Monday, July 23, 2007

Griffith UNiversity Brisbane Science seeks cures in exotic australia.

The country that produced such oddities as the planet’s only egg-laying, duck billed, mammal could also hold the secret to curing cancer, researchers believe. Home to the world’s weirdest, wildest plants and animals, Australia’s little-understood outback is now at the centre of an A$100 million project to reveal untapped sources of drug compounds from natural products.

read more

Tuesday, March 27, 2007

China, Australia to collaborate on genetic research

Australian and Chinese researchers have agreed to collaborate on a new genetic research project to find a link between genes and diseases.

They will use the information gathered to develop new medicines that can help people according to their specific genetic make-up.

Liver disease and obesity are just two conditions that can benefit from a better understanding of human genes and personally-targeted drug treatments.

The director of the China-Australia Centre for Phenomics Research, Dr Ed Bertram, has told Radio Australia's Connect Asia program, the project will be fast-tracking research by many years.

He says they are teaming up with the Beijing Genomics Institute, a world leader in genome sequencing technology for more than 10 years.

"One of the key projects that we will be working with is to build a large-scale library of some 10,000 unique fully-sequenced genetic mice with mutations of every gene in the genome," he said.

"Researchers can then access to study or validate genes from the human genome sequences for finding cause and mutations that are involved in disease."

Dr Bertram says the information will allow them to develop new therapies and drugs, as well as look at current drugs and treatments and their suitability for patients.

The China-Australia Centre, located at the Australian National University in Canberra, was one of four joint research centres set up with the support of the Australian and Chinese governments in 2008.

Dr Bertram says the new initiative is the start of a long-term partnership.

"It's really the latest technology development that will allow us to rapidly increase that output," he said.

"And we've found working with China to be a very good collaboration, particularly in this area."

 

source: Radio Australia News

Wednesday, March 14, 2007

Biocon arm partners Bristol-Myers

Syngene International Pvt. Ltd., a subsidiary of Biocon, has formed a research partnership with Bristol-Myers Squibb.

The initiative is to provide research and development services for discovery and early drug development, Biocon said here on Wednesday.

Bristol-Myers Squibb will significantly increase the scope of its existing relationship with Syngene to develop integrated capabilities in medicinal chemistry, biology, drug metabolism and pharmaceutical development.

The partnership will include a dedicated research facility at the Biocon Park here which will eventually house a team of 400 scientists.

Biocon Chairperson, Kiran Mazumdar-Shaw, said, "The new research facility will take us forward in our evolution as a vaulable partner to the global pharma industry. Syngene has advanced capabilities in high-end services in discovery research." This one-of-its kind alliance in the biotech sector will leverage the current global demand for `bio-partnering' and access to top scientific talent in India for the overseas partner.

Chief Scientific Officer and President, Pharmaceutical Research, Bristol-Myers Squibb, Elliott Sigal, said, "This broad expansion of R&D in India will allow us to grow competitively and provide access to world-class talent to deliver and grow our robust product pipeline."

Syngene International is a custom research company that does research for client companies across the world and has multi-disciplinary skills in synthetic chemistry and molecular biology. It also leverages the convergence of information technology and biotechnology to conduct early stage drug discovery and was started in 1994.

Microsoft Announces Synthetic Biology Grants

Microsoft Research (MSR) has announced the six winners of its inaugural grants in synthetic biology. The company issued a request for proposals a few months ago, seeking to identify outstanding research projects aimed at tackling the computational challenges in two areas of synthetic biology:
  • The re-engineering of natural biological pathways to produce interoperable, composed, biological parts; and
  • The development of tools and information repositories relating to the use of DNA in the fabrication of nanostructures and nanodevices

The company said that 49 proposals were submitted from 11 countries, including many leading researchers and labs in the field. Following external peer review, six proposals were chosen. They are as follows:

  • Computational Interchange Standards for Synthetic Biology -- Herbert Sauro, University of Washington
  • Design and Synthesis of Minimal and Persistent Protein Complexes -- David Green and Steven Skiena, Stony Brook University
  • BioStudio: A Collaborative Editing and Revision Control Environment for Synthetic Genomes -- Joel Bader and Jef Boeke, Johns Hopkins University School of Medicine
  • Identification of Standard Gene Regulatory Sequences for Synthetic Biology -- Robert Holt, University of British Columbia, Canada
  • Using programmable stacking bonds to combine DNA origami into larger, more complex, reconfigurable structures -- Paul Rothemund and Erik Winfree, California Institute of Technology
  • Noise Suppression and Next-Generation Cloning Vectors -- Johan Paulsson, Harvard University

Summaries of the six selected research abstracts can be found here.

In announcing the program in December, MSR Bioinformatics Program Manager Simon Mercer said the challenges faced by scientists today will be faced by business tomorrow and eventually by everyone. “Encouraging and participating in basic research helps us to better understand these problems and their potential solutions.” Synthetic biology is a particularly interesting field, Mercer said, because it has “the potential to provide insights into living systems, transform biotechnology and perhaps generate entirely new industries.”

Gene therapy for blindness clears hurdle in mice

researchers have used an experimental therapy in mice to shut down a gene that plays a crucial role in a leading cause of inherited blindness.

The technique, detailed in an upcoming issue of Vision Research, involves injecting the eye with a bit of genetic material called interfering RNA, which helps disable the gene.

Normally the gene is essential for healthy eyesight, but mutated versions of it are passed from generation to generation in some families and can lead to blindness.

Disabling the gene is a step toward developing a gene therapy to treat people with retinitis pigmentosa, an inherited disease that attacks the light-sensing cells in the eye. It affects about one in 60,000 people, with an estimated 1.5 million people afflicted worldwide.

Read the complete article here

Monday, February 19, 2007

Systems and Synthetic Biology

Editors-in-Chief: P.K. Dhar; R. Weiss


Systems and Synthetic Biology is a new biomedical journal publishing original papers and articles on all aspects of Systems and Synthetic Biology.

Systems Biology is an integrated approach to study collective behaviour of biological interactions. The grand challenge in Systems Biology is to connect molecular topography with physiological responses. Systems Biology field will realize its fullest potential once individual contributions are tied to variations in the system level behavior.

The emerging field of synthetic biology combines knowledge from various disciplines including molecular biology, engineering, mathematics, and physics to design and implement new cellular behaviors. The goal of synthetic biology is both to improve our quantitative understanding of natural phenomenon as well as to foster an engineering discipline for obtaining new complex cell behaviors in a predictable and reliable fashion. Systems and Synthetic Biology will publish research articles that either advance this field as an engineering discipline or use synthetic biology to improve our scientific knowledge of existing phenomena.

Synthetic biology: new engineering rules for an emerging discipline

I came across this very informative article...it's really long, but very good..

Synthetic biologists engineer complex artificial biological systems to investigate natural biological phenomena and for a variety of applications. We outline the basic features of synthetic biology as a new engineering discipline, covering examples from the latest literature and reflecting on the features that make it unique among all other existing engineering fields. We discuss methods for designing and constructing engineered cells with novel functions in a framework of an abstract hierarchy of biological devices, modules, cells, and multicellular systems. The classical engineering strategies of standardization, decoupling, and abstraction will have to be extended to take into account the inherent characteristics of biological devices and modules. To achieve predictability and reliability, strategies for engineering biology must include the notion of cellular context in the functional definition of devices and modules, use rational redesign and directed evolution for system optimization, and focus on accomplishing tasks using cell populations rather than individual cells. The discussion brings to light issues at the heart of designing complex living systems and provides a trajectory for future development.

Read the rest of the article here

Synthetic Biology is 'Extreme Genetic Engineering' and Far More Dangerous

A new report by the ETC Group concludes that the social,
environmental and bio-weapons threats of synthetic biology surpass
the possible dangers and abuses of biotech. The full text of the 70-
page report, Extreme Genetic Engineering: An Introduction to
Synthetic Biology, is available for downloading free-of-charge on the
ETC Group website: www.etcgroup.org

"Genetic engineering is passe," said Pat Mooney, Executive Director
of ETC Group. "Today, scientists aren't just mapping genomes and
manipulating genes, they're building life from scratch - and they're
doing it in the absence of societal debate and regulatory oversight,"
said Mooney.

Synbio - dubbed "genetic engineering on steroids" - is inspired by
the convergence of nano-scale biology, computing and engineering.
Using a laptop computer, published gene sequence information and mail-
order synthetic DNA, just about anyone has the potential to construct
genes or entire genomes from scratch (including those of lethal
pathogens). Scientists predict that within 2-5 years it will be
possible to synthesise any virus; the first de novo bacterium will
likely make its debut in 2007; in 5-10 years simple bacterial genomes
will be synthesised routinely and it will become no big deal to
cobble together a designer genome, insert it into an empty bacterial
cell and - voila - give birth to a living, self-replicating organism.
Other synthetic biologists hope to reconfigure the genetic pathways
of existing organisms to perform new functions - such as
manufacturing high-value drugs or chemicals.

A clutch of entrepreneurial scientists, including the gene maverick
J. Craig Venter, is setting up synthetic biology companies backed by
government funding and venture capital. They aim to commercialise new
biological parts, devices and systems that don't exist in the natural
world - some of which are designed for environmental release.
Advocates insist that synthetic biology is the key to cheap biofuels,
a cure for malaria, and climate change remediation - media-friendly
goals that aim to mollify public concerns about a dangerous and
controversial technology. Ultimately synthetic biology means cheaper
and widely accessible tools to build bioweapons, virulent pathogens
and artificial organisms that could pose grave threats to people and
the planet. The danger is not just bio-terror, but "bio-error," warns
ETC Group.

Despite calls for open source biology, corporate and academic
scientists are winning exclusive monopoly patents on the products and
processes of synthetic genetics. Like biotech, the power to make
synthetic life could be concentrated in the hands of major
multinational firms. As gene synthesis becomes cheaper and faster, it
will become easier to synthesise a microbe than to find it in nature
or retrieve it from a gene bank. Biological samples, sequenced and
stored in digital form, will move instantaneously across the globe
and be resurrected in corporate labs thousands of miles away - a
practice that could erode future support for genetic conservation and
create new challenges for international negotiations on biodiversity.

"Last year, 38 civil society organizations rejected proposals for
self-regulation of synthetic biology put forth by a small group of
synthetic biologists," said Kathy Jo Wetter of ETC Group. "Widespread
debate on the social, economic and ethical implications of synbio
must come first - and it must not be limited to biosecurity and
biosafety issues," said Wetter.

The tools for synthesising genes and genomes are widely accessible
and advancing at break-neck pace. ETC Group's new report concludes
that it is not enough to regulate synthetic biology on the national
level. Decisions must be considered in a global context, with broad
participation from civil society and social movements. In keeping
with the Precautionary Principle, ETC Group asserts that - at a
minimum - there must be an immediate ban on environmental release of
de novo synthetic organisms until wide societal debate and strong
governance are in place.

The Dangers of Synthetic Biology

Nobel Prize winner David Baltimore explains why building smallpox from scratch is a key safety concern in synthetic biology.

The emerging field of synthetic biology -- the quest to design and build new life forms that can perform useful functions -- brings exciting promise and potentially dangerous capabilities. Scientists have the ability to synthesize entire strings of DNA and put together complicated molecular machinery. But that power has raised some troubling questions. Could terrorists recreate viruses such as smallpox? Or engineer a virus even more deadly than avian flu? (see "The Knowledge").

In the 1970s, scientists faced a similar dilemma. The advent of recombinant DNA technology meant biologists could manipulate DNA as they never could before. Concerned about the potential perils of this new tool, a prominent group of scientists held the now-famous Asilomar Conference in 1975 (formally titled the "International Congress on Recombinant DNA Molecules") to determine how to proceed safely.

Thirty years later, at the Synthetic Biology 2.0 meeting at the University of California, Berkeley this month, scientists met to discuss not only new developments in the field, but also how the community should deal with the growing safety concerns surrounding synthetic biology.

David Baltimore, a winner of the 1975 Nobel Prize in physiology or medicine, and president of the California Institute of Technology, was one of the organizers of the Asilomar Conference. At the Synthetic Biology conference last week, he reflected on changes in the field over the last 30 years. Baltimore talks here with Technology Review about what scientists have learned since 1975 and the specific dangers we should be most worried about.

Technology Review: What were you were most concerned about 30 years ago?

David Baltimore: The Asilomar Conference was convened in a very different context than we have today. We were marveling at a wholly new world of experimentation -- we literally had no experience with moving DNA around. But people were also concerned, and rightly so, about issues of intrinsic safety. They were worried, for example, that we could create organisms that we didn't know how to control.

At the conference, we decided to focus purely on safety, rather than ethics or biowarfare. We believed, somewhat naively, that there was a treaty that everyone held to prohibiting use of technology to make biological weapons. In retrospect, the U.S.S.R. had a huge clandestine program. We also didn't have the situation we have today, where terrorist organizations cross boundaries and are not held by treaties. So we clearly have an unfinished agenda from Asilomar on biowarfare.

TR: What issues are you most worried about today?

DB: The real danger today is from organisms that already exist. The idea of synthesizing something worse than that, of taking bits of Ebola and other viruses to create something more deadly, underestimates how hard it is to survive in the natural world.

Adapting to the human lifestyle is very complicated, so I would guess that we would fail if we tried to engineer a dangerous organism. Ebola, for example, is very pathogenic. It infects families and health workers, but it never spreads widely because it is too lethal -- it isn't in the community long enough to spread. Bird flu is not likely to spread widely until it mutates to become less pathogenic.


Read the full interview here

Next-Generation Retinal Implant


On Thursday, scientists at the University of Southern California (USC) announced their plans to test an improved retinal implant in blind patients. The new implant, which scientists hope will better improve patients' vision, has four times the resolution of the previous version.

"My expectation, without really knowing what is going to happen, is that this will be useful for people in allowing them to find a lit doorway or the edge of an object when going into a room," says James Weiland, a scientist at USC involved in the project.

People with retinal-degeneration diseases, such as retinitis pigmentosa and macular degeneration, lose their sight as the cells in the eye that normally sense light deteriorate. Retinal implants can take over for these lost cells, converting light into neural signals that are then interpreted by the brain. Simpler versions of these devices, developed by researchers at USC and other institutions, have already been tested in humans, giving patients rudimentary vision, such as the ability to detect light and to occasionally distinguish between simple objects. One patient, for example, wears the device to her grandson's soccer games and reports that she perceives the sensation of the players' movement as they run by, says Weiland.

The device, developed by Mark Humayun and colleagues at USC, consists of a tiny chip dotted with hair-thin electrodes. When implanted in the retina, the electrodes transmit electrical signals from the chip to neural cells in the eye, which then send the message to the brain. A wireless camera mounted on glasses and a video processing unit worn on the belt capture and process visual information from the wearer's surroundings and wirelessly transmit those signals to the chip.

The new version of the implant, which the researchers have been working on for the past eight years, has nearly quadrupled the number of electrodes--from 16 to 60--and is about half the size of the previous model. The researchers recently received permission from the Food and Drug Administration to start human tests, which they plan to begin in the next few months.

Once the device is implanted, researchers will need to do extensive tests to figure out how to optimize it. "A camera gets at least tens of thousands of pixel information, and we need to transmit that to just 60 stimulating channels," says Weiland. "We have to figure out what is the most important information to keep."

Read the rest of the article here

Friday, February 16, 2007

New DNA test in Anna Nicole Smith case



i know.. i know... but it's still about what genetics can do!!

A judge ordered another DNA sample be taken fromAnna Nicole Smith's body Thursday as he heard often fiery arguments in the fight over the former Playboy Playmate's remains and custody of her infant daughter.

The swab of Smith's cheek was to be taken in the afternoon, despite the objections of attorneys for her longtime companion, Howard K. Stern, and her estranged mother, Vergie Arthur, and testimony from the medical examiner and DNA experts that such an additional sample was likely not necessary.

Circuit Judge Larry Seidlin said he wanted to make sure all samples were taken before Smith was buried, so her body wouldn't have to be exhumed.

"When we bury her, I want it to be forever," he said in the second day of an emergency hearing.

Smith, 39, died Feb. 8 after collapsing at a Florida hotel.

As the proceedings dragged on, investigators in the Bahamas went into a mansion that Stern and Smith shared, though the officers declined to say why they were there. Stern filed a burglary report claiming a computer, home videos and other items were taken from the house after Smith's death.

Stern claims he is executor of Smith's will and wants to have her buried next to her son in the Bahamas. Arthur wants her daughter buried in her home state of Texas.

"She sits here today to take her to Texas and put her in the ground all alone ... and it's sad and it's sick," Stern's lawyer, Krista Barth, told the judge in attacking Smith's mother.

Arthur's attorney, Stephen Tunstall, said his client "wants to take her home to Texas to bury her with the rest of her family." Arthur wiped tears away outside an elevator during a break in the proceedings.

Photographer Larry Birkhead hopes DNA taken from Smith will help prove he fathered the former centerfold's 5-month-old daughter, Dannielynn, who could inherit millions.

The judge has said the dispute could be lengthy. The hearing, which began Wednesday, stretched into the afternoon Thursday and was to continue Friday.

Debra Opri, an attorney for Birkhead, said earlier in a news release that she was satisfied DNA samples would be provided by Florida authorities. Opri has said Smith's DNA is needed to connect her with Dannielynn, and to help prove there was no baby switch.

Prince Frederic von Anhalt, the husband of the actress
Zsa Zsa Gabor, has said he had a decade-long affair with Smith and may also be the father. He filed legal documents Thursday in California seeking a DNA test to determine if he is the father of the baby.

Smith's body remained at the medical examiner's office, and Seidlin said it would stay there. "This body's not leaving Broward County till I make the ruling."

Smith was the widow of Texas oil tycoon J. Howard Marshall II, whom she married in 1994 when he was 89 and she was 26. She had been fighting his family over his fortune since his death in 1995.

A judge in the Bahamas issued an injunction Tuesday preventing the baby from being taken out of the country until the custody case is resolved.

Arthur wants to be named guardian of her granddaughter and sought the order because she feared Stern would take the child from the Bahamas, her lawyer said.

Thursday, February 15, 2007

Your Genetic Destiny for Sale

I found this article while browsing around... it's a very old one.. almost 6 years old..2001 i think.. but totally fascinating. I'm not publishing the whole article here, it's about 6 pages long.

Large extended families have traditionally been the mother lode of genetic research. From them came a precious commodity: links between the presence of a disease and the errant genes responsible for it. When medical researcher Nancy Wexler, for instance, went looking for the genetic cause of Huntington's disease in 1979, it was a 9,000-member Venezuelan family that enabled her to trace the telltale patterns of disease inheritance.

Wayne Gulliver's family is not nearly so large, but it is impressive nonetheless. Until two years ago, when his great-great-aunt passed away, six generations of Gullivers were alive in Newfoundland. His grandmother, who died last October, had some hundred descendants, while his parents, only in their 60s, already have 26 grandchildren to go with their 10 children. All of this would be professionally irrelevant if Gulliver's family were not typical of Newfoundland, and if Gulliver himself, a dermatologist who studies the genetics of psoriasis, were not involved in a rapidly emerging discipline called population genomics, the goal of which is to identify the underlying genes responsible for common chronic diseases, such as cancer and heart disease.

Two years ago Gulliver met Paul Kelly, CEO of the British company Gemini Genomics, which had already assembled a huge international network of twins to use in searching for gene-disease associations. Gulliver pitched Kelly the idea of supplementing Gemini's database with population statistics from Newfoundland and Labrador. His selling points were simple: a population of 550,000, of which almost 90 percent are descended from the original Irish, Scottish and English immigrants who arrived before the mid-19th century. It is, Gulliver says, a population in which the locals often know their family lineages back to the original immigrants. "Not like the States," he says, "where you have three kids, send them off to college, and you might be lucky if you see each other every fifth Thanksgiving."

And many of those families, like Gulliver's own, are large. In such a tightly knit population consisting of large extended families, common diseases might run in recognizable patterns-shared by siblings, for instance, or passing through paternal or maternal lines, or linked to other distinctive physical characteristics. All it would take to mine this rich vein of medical history for valuable clues to disease-causing genes would be a sufficient effort, some very advanced biotechnology tools and some startup capital.

Gulliver's pitch prompted Gemini to launch Newfound Genomics in February 2000. In the near term, Newfound Genomics aims to concentrate on diseases endemic to the local population-psoriasis, diabetes, obesity, inflammatory bowel disease, osteoporosis and rheumatoid arthritis-with the hope, considering the Irish/English/Scottish ancestry, that any relevant genes or gene variants that might be uncovered would play significant roles in other populations. The expectations behind the company are anything but modest, at least judging by the inaugural press release. "We have the potential here to develop a major international powerhouse of clinical genetics," said Kelly, "that will provide benefit not only for the Newfoundland and Labrador community but also patients suffering from these diseases worldwide."


To read the entire article click here

Can RNA Turn Genes On?

Researchers at the University of Texas Southwestern Medical Center have found that RNA may be a potential tool in activating dormant genes.

RNA--a tiny cousin of DNA that may be the key to developing genetic therapies for a huge range of diseases, including cancer, neurological and respiratory diseases, and HIV. Nearly eight years ago, researchers Craig Mello, of the University of Massachusetts Medical School, and Andrew Fire, of Stanford University's School of Medicine, discovered that RNA plays a crucial role in regulating gene expression: the ability to turn genes off. They won a Nobel Prize for their work in 2006 identifying the mechanism for a process called RNA interference, or RNAi. They found that RNA blocks a gene from delivering its message to proteins, essentially shutting down that gene. Since then, scientists around the world have run with the idea, finding ways for RNAi to turn off a variety of genes--in particular, those that cause disease. It's RNA's role in switching off genes that dominates the talks at this week's conference, titled "RNAi for Target Validation and as a Therapeutic."

read the rest of the story here

Human Model Completed

Researchers at the University of California, San Diego, have constructed the first complete computer model of human metabolism. Available free on the Web, the model is a major step forward in the fledging field of systems biology, and it will help researchers uncover new drug pathways and understand the molecular basis of cancer and other diseases.

Metabolism is the sum of all chemical reactions involved in breaking down the nutrients in food into energy and using them as the raw materials for making everything the body needs, from hormones like insulin to the lipids that make up cell membranes. The computer model of metabolism, constructed by researchers in the lab of Bernhard Palsson, professor of bioengineering, connects all such known chemical reactions in the body to every human gene.

Read the whole story here

Monday, February 05, 2007

Sea Urchin Genome Is Sequenced

When scientists sequenced the sea urchin genome, they found surprising similarities to that of human beings AND are putting it to good use...

Who would have guessed that the lowly sea urchin, that brain-less, limb-less porcupine of the sea, would be the star of a multi-million dollar, worldwide effort to map out every letter of its genetic code? Or that the information gathered in that effort may eventually lead to new treatments for cancer, infertility, blindness, and diseases like muscular dystrophy and Huntington's Disease?

James Coffman, Ph.D., of the Mount Desert Island Biological Laboratory in Bar Harbor was one of the scientists who helped decode the 814 million pairs of nucleotide bases in the sea urchin's chromosomes. The Human Genome Sequencing Center at Baylor College of Medicine in Texas led the project and announced the completion of the three-year project today. Having the complete genome, Coffman says, "makes doing research on urchins so much easier."

Why would anyone want to do biomedical research on sea urchins? According to Coffman, sea urchins are remarkably similar to humans in many ways, sharing most of the same gene families, and yet differ in a few critical areas besides the obvious physical ones. For one thing, sea urchins have a "extraordinarily complex innate immune system" which is not based on antibodies, like that of jawed vertebrates, but is effective enough to give sea urchins a surprisingly long life span of up to a hundred years or more.

Read the whole story here

Regards

Genetic map offers new tool for malaria research

Did you know that the malaria Parasite's DNA has nearly 47,000 genetic variations worldwide; kills every 30 seconds??

An international research team has completed a map that charts the genetic variability of the human malaria parasite, Plasmodium falciparum. The work, published in the Dec. 10 advance online edition of Nature Genetics, has already unearthed novel genes that may underlie resistance to current drugs against the disease.

The study reveals striking variation within the pathogen's genome, including an initial catalog of nearly 47,000 specific genetic differences among parasites sampled worldwide. That's more than double the expected level of diversity in the parasite's DNA. These differences lay the foundation for dissecting the functions of important parasite genes and for tracing the global spread of malaria.

The scientists who created the map are from the Broad Institute of MIT and Harvard, the Harvard School of Public Health and Cheikh Anta Diop University in Senegal, where malaria is endemic.

"Malaria remains a significant threat to global public health, driven in part by the genetic changes in the parasite that causes the disease," said senior author Dyann Wirth, a professor at the Harvard School of Public Health and co-director of the Broad Institute's Infectious Disease Initiative. "This study gives us one of the first looks at genetic variation across the entire malaria parasite genome--a critical step toward a comprehensive genetic tool for the malaria research community."

Plasmodium falciparum--the deadliest of the four parasites that cause malaria in humans--kills one person every 30 seconds, mostly children living in Africa. Despite decades of research, the genetic changes that enable it to escape the body's natural defenses and to overcome malaria drugs remain largely unknown.

To gain a broad picture of genetic variability--worldwide and genome-wide--the scientists analyzed more than 50 different P. falciparum samples from diverse geographic locations. This includes the complete genome sequencing of two well-studied samples, as well as extensive DNA analyses of 16 additional isolates.

By comparing the DNA sequences to each other and to the P. falciparum genome sequenced in 2002, the researchers uncovered extensive differences, including 47,000 single-letter changes called single nucleotide polymorphisms (SNPs). Although there are probably many more SNPs to be found, this initial survey provides a launching point for future systematic efforts to identify parasite genes that are essential to malaria.

"The roles of most of the malaria parasite's genes are still not known," said Sarah Volkman, a research scientist at the Harvard School of Public Health. "An important application of this new tool will be in pinpointing the genes that are vital to the development and spread of malaria."

Volkman and Pardis Sabeti, a postdoctoral fellow at the Broad Institute, are first authors on the paper.

One of the map's strengths is its ability to reveal evolutionary differences among parasites. This information can shed light on the genes responsible for malaria drug resistance--a major obstacle to adequate control of the disease.

Using the map to compare parasites exposed to different anti-malarial drugs, the scientists identified a novel genome region that is strongly implicated in resistance to the drug pyrimethamine, and also confirmed a region of the genome known to be involved in chloroquine drug resistance.

"The same genetic principles used to study human evolution can provide important clues about malaria," said Sabeti. "This tool has already yielded insights into the genetic changes that correlate with different drug treatments, pointing us to genes that may contribute to drug resistance."

The map can also define the genetic landscapes of different parasite populations. Applying it to parasites from various continents, the scientists discovered greater DNA variability among P. falciparum samples from Africa relative to those from Asia and the Americas. This knowledge guides the selection of genetic markers to track the transmission of distinct parasites, particularly ones that are virulent or drug resistant. It also lays the groundwork for connecting parasite genes with traits that vary geographically and bolster malaria's foothold in many parts of the world.

"Genomic tools have largely been applied to First World diseases up to now. This project underscores the power and importance of applying them to the devastating diseases of the developing world," said Eric Lander, one of the study's authors and the director of the Broad Institute. "By joining forces among scientists in the U.S., Africa and elsewhere, it should be possible to rapidly reveal the genetic variation in malaria around the world.

"Knowing the enemy will be a crucial step in fighting it," said Lander, who is also a professor of biology at MIT and a member of the Whitehead Institute for Biomedical Research.

The work is one of three large-scale studies of the parasite's DNA that appear together in Nature Genetics. It was supported by the Bill and Melinda Gates Foundation, the Burroughs-Wellcome Fund, the Exxon Mobil Foundation, the National Institutes of Allergy and Infectious Disease Microbial Sequencing Center and the National Institutes of Health.

MIT improves protein sorting with a new microchip

A new MIT microchip system promises to speed up the separation and sorting of biomolecules such as proteins. The work is important because it could help scientists better detect certain molecules associated with diseases, potentially leading to earlier diagnoses or treatments.

The microchip system has an extremely tiny sieve structure built into it that can sort through continuous streams of biological fluids and separate proteins accurately by size. Conventional separation methods employ gels, which are slower and more labor-intensive to process. The new microchip system could sort proteins in minutes, as compared to the hours necessary for gel-based systems.

The MIT team's results appear in the Feb. 5 issue of Nature Nanotechnology.

The new technology is an advance from a one-dimensional sieve structure reported by the same MIT group last year. The key to this new advance, called an anisotropic nanofluidic sieving structure, is that the researchers have designed the anisotropic sieve in two orthogonal dimensions (at a right angle), which enables rapid continuous-flow separation of the biological sample. This allows continuous isolation and harvesting of subsets of biomolecules that researchers want to study. And that increases the probability of detecting even the smallest number of molecules in the sample.

"With this technology we can isolate interesting proteins faster and more efficiently. And because it can process such small biologically relevant entities, it has the potential to be used as a generic molecular sieving structure for a more complex, integrated biomolecule preparation and analysis system," said Jongyoon Han, the Karl Van Tassel Associate Professor of Electrical Engineering and associate professor of biological engineering at MIT and head of the MIT team.

Han's coauthors of the Nature Nanotechnology paper are co-lead authors Jianping Fu, a Ph.D. candidate in the Department of Mechanical Engineering, and Reto B. Schoch, a postdoctoral associate in the Research Laboratory of Electronics (RLE). Additional authors are Anna Stevens, a postdoctoral associate in the Harvard-MIT Division of Health Sciences and Technology, and Professor Steven Tannenbaum of MIT's Biological Engineering Division.

Han noted that until the late 1990s, most advances in biological laboratory equipment were aimed at the Human Genome Project and discoveries related to DNA, which are larger molecules compared to proteins. However, because of the vital role proteins play in almost all biological processes, researchers began to focus their attention on proteins. But one obstacle has been the lack of good laboratory tools with which to prepare biological samples to analyze proteins, said Han, who also has affiliations in MIT's RLE, Computational and Systems Biology Initiative, Center for Materials Science and Engineering and Microsystems Technology Laboratories.

"I shifted my attention from DNA into the area of protein separation around 2002 with the shift to proteomics (the study of proteins)," Han said. "But the field was using decades-old gel electrophoresis technology. There is a big gap in the need for technology in this area."

Han and Fu therefore devised the anisotropic sieve that is embedded into a silicon chip. A biological sample containing different proteins is placed in a sample reservoir above the chip. The sample is then run through the sieve of the chip continuously. The chip is designed with a network of microfluidic channels surrounding the sieve, and the anisotropy (directional property) in the sieve causes proteins of different sizes to follow distinct migration trajectories, leading to efficient continuous-flow separation. The current sieve has an array of nanofluidic filters of about 55 nanometers, or billionths of a meter, wide.

"The proteins to be sorted are forced to take two orthogonal paths. Each path is engineered with different sieving characters. When proteins of different sizes are injected into the sieve under applied electric fields, they will separate into different streams based on size," Han explained. At the bottom of the chip the separated proteins are collected in individual chambers. Scientists then can test the proteins.

While other scientists have used similar continuous flow techniques to separate large molecules like long DNA, the MIT team succeeded with the tinier proteins. "This is the first time physiologically relevant molecules like proteins have been separated in such a manner," said Han. "We can separate the molecules in about a minute with the current device versus hours for gels."

Another advantage of the microchip is that it can have so many different pore sizes, and unlike gels, it is possible to design an exact pore size to increase the separation accuracy. That in turn can help researchers look for so-called biomarkers, or proteins that can reveal that disease is present, and thus help researchers develop diagnostics and treatments for the disease. "Sample preparation is critical in detecting more biomarker signals," said Han.

Funding came from the National Science Foundation, the National Institutes of Health and the Singapore-MIT Alliance.

Wednesday, January 31, 2007

Nutrigenomics - Eat according to your genome


If you knew that you were especially susceptible to heart disease when you gained weight, would it increase your motivation to diet? How much would you be willing to pay to find out if you are one of the lucky people who can eat as much fat as you want and not have an increased risk of heart disease? Such tests are the goal of nutrigenomics, which seeks to identify the links between nutrition and disease based on an individual's genome.

While the field is still too young to offer personal dietary advice for the average consumer, research has uncovered links among genes, diet, and heart disease. Jose Ordovas, director of the Nutrition and Genomics Laboratory at Tufts University, has spent years studying the link between metabolism of dietary fats and risk of cardiovascular disease. After analyzing data from the Framingham Heart Study, a large-scale study that has traced the health of some 5,000 people since 1948, his team has found that certain genetic variants can protect people from diet-induced cardiovascular disease--or put them at increased risk. Ordovas spoke with Technology Review about his research and the future of the field.

Is It Anthrax or Just White Powder?

A good article about A microfluidic chip that rapidly identifies pathogens by scanning their genomes.

From the article :

When a patient is admitted to the hospital with signs of a dangerous systemic bacterial infection, or when a post-office worker finds white powder in a suspicious-looking envelope, the ability to quickly identify potential pathogens is important. To accomplish that, a team of Massachusetts researchers is developing a microfluidic chip that performs fast DNA sequencing to rapidly identify bacteria. The goal is a device simple enough to use in airport and other security screening.

In order to identify the bacteria in a blood sample or in a building's ventilation system, researchers or clinicians usually must start by coaxing it to grow in culture in the lab. This takes about 14 to 48 hours. In the meantime, a patient with a drug-resistant infection may be given the wrong antibiotic, or emergency medical workers may miss the signs of a potential bioterror attack.

Click here to read the full story


Monday, January 29, 2007

RNA used to turn on genes to alleviate disease

The gene-activating method, which is being developed by UT Southwestern scientists, also is providing researchers with a novel research tool to investigate the role that genes play in human health.

In a paper appearing online at Nature Chemical Biology and in an upcoming edition of the journal, lead author Dr. Bethany Janowski, assistant professor of pharmacology at UT Southwestern, and her colleagues describe how they activated certain genes in cultured cells using strands of RNA to perturb the delicately balanced mixture of proteins that surround chromosomal DNA, proteins that control whether genes are turned on or off.

Dr. David Corey, professor of pharmacology and the paper's senior author, said the results are significant because they demonstrate the most effective and consistent method to date for coaxing genes into making the proteins that carry out all of life's functions - a process formally called gene expression.

In any medical specialty, Dr. Janowski said, there are conditions where increased gene expression would prove beneficial.

"In some disease states, it's not that gene expression is completely turned off, but rather, the levels of expression are lower than they should be," she said. As a result, there is an inadequate amount of a particular protein in the body. "If we can bring the level up a few notches, we might actually treat or cure the disease," Dr. Janowski said.

For example, some genes are natural tumor suppressors, and using this method to selectively activate those genes might help the body fend off cancer, Dr. Janowski said.

Genes are segments of DNA housed in chromosomes in the nucleus of every cell and they carry instructions for making proteins. Faulty or mutated genes lead to malfunctioning, missing or over-abundant proteins, and any of those conditions can result in disease.

Surrounding the chromosome is a cloud of proteins that helps determine whether or not a particular gene's instructions are "read" and "copied" to strands of messenger RNA, which then ferry the plans to protein-making "factories" in the cell.

In its experiments, the UT Southwestern team used strands of RNA that were tailor-made to complement the DNA sequence of a specific gene in isolated breast cancer cells. Once the RNA was introduced into the protein mix, the gene was activated, ultimately resulting in a reduced rate of growth in the cancer cells.

Dr. Corey said that while it's clear the activating effects of the new technique are occurring at the chromosome level, and not at the messenger RNA level, more research is needed to understand the exact mechanism.

Although the RNA strands the researchers introduced - dubbed antigene RNA - were manufactured, Dr. Corey said the process by which they interact with the chromosome appears to mimic what naturally happens in the body.

"One of the reasons why these synthetic strands work so well is that we're just adapting a natural mechanism to help deliver a man-made molecule," Dr. Corey said. "We're working with nature, rather than against it."

Drs. Corey's and Janowski's current results are built on previous work, published in 2005 in Nature Chemical Biology, in which they found that RNA strands could turn off gene expression at the chromosome level.

The new UT Southwestern research, coupled with that from 2005, demonstrates a shift away from conventional thinking about how gene expression is naturally controlled, as well as how scientists might be able to exploit the process to develop new drug targets, Dr. Corey said.

For example, current methods to block gene expression, such as RNA interference, rely on using RNA strands to intercept and bind with messenger RNA. While RNA interference is an effective tool for studying gene expression, Dr. Janowski said, it's more efficient to use RNA to control both activation and de-activation at the level of the chromosome.

"It goes right to the source, right to the faucet to turn the genes on or off," she said.

Dr. Corey said many researchers have the ingrained idea that RNA only targets other RNA - such as what occurs when messenger RNA is targeted during RNA interference. "That's what everyone is familiar with," he said. "But the idea of RNA being used as a sort of nucleic acid modulator of chromosomes, at the level of the chromosome itself, is novel and unexpected, and it's going to take some getting used to."

http://www.utsouthwestern.edu/

Saturday, January 27, 2007

Synthetic Biology 3.0

oiy! it's almost wierd that everything is being tagged as a number, web 2.0, synthetic bio 2.0, blog 2.0, whew! what next???

yep.. Synthetic Biology 3.0!!

The conference is gonna be held on the 24th to 27th June 2007, at Zurich Switzerland (did i spell that right??) anyway, stay tuned as we have more of this coming up...

http://www.syntheticbiology.ethz.ch/conf_2007

Cheers!

Friday, January 26, 2007

The Biggest DNA Ever Made

Again I stress that this is old news...but here's the thing.. I was looking around the other day for the longest DNA ever made (synthetic ofcourse) and look what i found on forbes.com

there are some links here which will take u to forbes.com
We've already mentioned about Codon Devices earlier..click here to read it..

Matthew Herper, 07.13.06, 6:00 AM ET

A tiny startup says it has created a stretch of DNA more than 35,000 letters long.

The company, Codon Devices of Cambridge, Mass., believes it is the longest piece of DNA ever ever commercially shipped--but that's only the latest step in a race to create bigger and bigger pieces of genetic material.

Codon is aiming to become the leading player in a new field called "synthetic biology," creating tools by which cells and their genetic material can be more precisely engineered in order to create new medicines and industry. In this case, the DNA was constructed for Microbia, another Cambridge biotech that is developing drugs and creating microbes that can be used in manufacturing chemicals.

The creation of ever-longer stretches of man-made DNA is allowing researchers to make new strides in understanding how multiple genes work together.

"This is basically the next step in synthetic biology," says Brian Baynes, Codon's chief scientific officer. "People have been doing a lot of work with synthetic genes for a number of years, but they've been stuck with one gene."

On a piece of DNA as long as the one made for Microbia, ten or more genes may be present. By studying more than one gene at once, researchers hope to get a better picture of how they work in concert to produce an organism. Another advantage: These stretches can also be made to contain all the DNA letters that occur between genes. Scientists once thought of that stuff as junk, but many now believe it may regulate how the genes work or provide some other function.

Scientists playing in the synthetic-biology toolbox have also managed to make living cells do things nature never designed. One setup created blinking lights; another made photographic film composed of living bacteria in a Petri dish.

Codon was founded a year ago on the idea that scientists would need a company that could sell tools used in creating such custom-designed biological systems (see: " Photoshop For DNA").

Other companies are also in the business of making DNA for drug companies and other research organizations, which save time by using newer DNA synthesis methods instead of laboriously copying cells and inserting or deleting bits of genetic material.

Blue Heron Biotechnology, a company that is in the sole business of synthesizing DNA, says it made a piece of DNA that was 27,000 letters long while working with academic researchers. But the company says it sees itself as more of a supplier to synthetic biologists than as a player in the field. "I am optimistic that in a few years things like synthetic biology will be half or more of our market," says Chief Executive John Mulligan. "We're a pure DNA foundry."

Codon says that within a year or two it hopes to create DNA fragments that are as much as 100,000 letters long, and that eventually they might make 1-million-letter fragments.

"Codon's charge from the beginning has been to industrialize this space and create something well beyond synthetic biology that we call constructive biology," says Chief Executive John Danner. He says that by December of this year he hopes to have more DNA production capacity than all his competitors currently have combined.

Awesome stuff considering its just a start up...while we look out even more, stay tuned because, this blog is soon gonna be the definative Gene Synthesis Blog

Invitrogen and Blue Heron Biotechnology Enter into Strategic Development and Distribution Relationship

CARLSBAD, Calif.--(BUSINESS WIRE)--Dec. 12, 2006--Invitrogen Corporation (Nasdaq:IVGN), a global leader in life sciences, today announced they have entered into a strategic development and distribution relationship with Blue Heron Biotechnology. Invitrogen will invest in Blue Heron in exchange for worldwide rights to distribute Blue Heron's custom gene synthesis services. Under the terms of the agreement, Invitrogen will become the exclusive worldwide distributor of Blue Heron's synthetic genes. The financial terms of the agreement were not disclosed.

Blue Heron Biotechnology's proprietary GeneMaker(R) platform can synthesize any gene sequence, with perfect accuracy regardless of length or complexity, which makes it ideal for the synthetic biology market. Researchers worldwide are increasingly turning to synthetic genes as a convenient, cost-effective alternative for traditional cloning. Accurate and rapid synthesis of synthetic genes has allowed pharmaceutical and biotechnology companies to speed the drug discovery process through an ability to rapidly and accurately synthesize known genes, and produce from them novel proteins, new vaccines and diagnostics.

"Invitrogen recognizes the tremendous new possibilities that gene synthesis offers life science researchers," said Nathan Wood, Vice President of Cloning and Protein Expression. "We have developed a broad array of products that complement Blue Heron's GeneMaker(R) platform and this agreement continues to enhance our portfolio offerings to our customers."

Invitrogen is a leading provider of recombinant cloning and protein expression products, as well as the premier provider of the largest fully sequenced human open reading frame clone collections. Gene synthesis builds upon this strength and will be especially useful in emerging fields such as synthetic biology.

"Partnering with a life sciences leader such as Invitrogen is an important milestone in Blue Heron Bio's continued growth and signals an important milestone for the overall gene synthesis market as well. We are very pleased to be able to make our gene synthesis services available through Invitrogen's unmatched distribution and marketing channels," said John Fess, CEO of Blue Heron Biotechnology.

As part of the agreement, the companies will co-develop new products and services for the research and bio-pharmaceutical markets.

Reactivated gene shrinks tumors, MIT study finds

Many cancers arise due to defects in genes that normally suppress tumor growth. Now, for the first time, MIT researchers have shown that re-activating one of those genes in mice can cause tumors to shrink or disappear.

The study offers evidence that the tumor suppressor gene p53 is a promising target for human cancer drugs.

"If we can find drugs that restore p53 function in human tumors in which this pathway is blocked, they may be effective cancer treatments," said David Kirsch of MIT's Center for Cancer Research and Harvard Medical School, one of the lead co-authors of the paper.

The study is published in the Jan. 24 online edition of Nature. It was conducted in the laboratory of Tyler Jacks, director of the Center for Cancer Research, the David H. Koch Professor of Biology and a Howard Hughes Medical Institute investigator.

P53 has long been known to play a critical role in the development of many tumors--it is mutated in more than 50 percent of human cancers. Researchers have identified a few compounds that restore p53 function, but until now, it has not been known whether such activity would actually reverse tumor growth in primary tumors.

The new MIT study shows that re-activating p53 in mouse tumors dramatically reduces the size of the tumors, in some cases by 100 percent.

"This study provides critical genetic evidence that continuous repression of a tumor suppressor gene is required for a tumor to survive," said Andrea Ventura, an Italian postdoctoral associate in the Center for Cancer Research and first author of the paper.

In normal cells, p53 controls the cell cycle. In other words, when functioning properly, it activates DNA repair mechanisms and prevents cells with damaged DNA from dividing. If DNA damage is irreparable, p53 induces the cell to destroy itself by undergoing apoptosis, or programmed cell death.

When p53 is turned off by mutation or deletion, cells are much more likely to become cancerous, because they will divide uncontrollably even when DNA is damaged.

In this study, the researchers used engineered mice that had the gene for p53 turned off. But, they also included a genetic "switch" that allowed the researchers to turn p53 back on after tumors developed.

Once the switch was activated, p53 appeared in the tumor cells and the majority of the tumors shrank between 40 and 100 percent.

The researchers looked at two different types of cancer--lymphomas and sarcomas. In lymphomas, or cancers of the white blood cells, the cancer cells underwent apoptosis within 1 or 2 days of the p53 reactivation.

In contrast, sarcomas (which affect connective tissues) did not undergo apoptosis but went into a state of senescence, or no growth. Those tumors took longer to shrink but the senescent tumor cells were eventually cleared away.

The researchers are not sure why these two cancers are affected in different ways, but they have started trying to figure it out by identifying the other genes that are activated in each type of tumor when p53 turns back on.

The study also revealed that turning on p53 has no damaging effects in normal cells. The researchers had worried that p53 would kill normal cells because it had never been expressed in those cells.

"This means you can design drugs that restore p53 and you don't have to worry too much about toxic side effects," said Ventura.

Possible therapeutic approaches to turn on p53 in human cancer cells include small molecules that restore mutated p53 proteins to a functional state, as well as gene therapy techniques that introduce a new copy of the p53 gene into tumor cells. One class of potential drugs now under investigation, known as nutlins, acts by interfering with MDM2, an enzyme that keeps p53 levels low.

In follow-up studies, the MIT researchers are looking at other types of cancer, such as epithelial (skin) cancer, in their mouse model, and they plan to see if the same approach will also work for tumor suppressors other than p53.

This research was funded by the Howard Hughes Medical Institute, the National Cancer Institute, the American Italian Cancer Research Foundation and the Leaf Fund.

Other authors on the paper are Margaret McLaughlin, a former postdoc in Jacks' lab, now at Novartis; David Tuveson, also a former postdoc, now group leader at the Cambridge Research Institute (United Kingdom); Laura Lintault, a research affiliate in the Center for Cancer Research; Jamie Newman, graduate student in MIT's Department of Biology; Elizabeth Reczek, a former graduate student in Jacks' lab, now a postdoctoral fellow at Brigham and Women's Hospital; Ralph Weissleder, a professor of radiology at Harvard Medical School and director of the Center for Molecular Imaging Research; and Jan Grimm, a former postdoc in Weissleder's lab, now at Memorial Sloan Kettering Cancer Center.

Genes and Chromosomes: The Building Blocks of Life


Every human being has 20,000 to 25,000 genes that determine the growth, development and functions of our physical and biochemical systems. Genes are normally packaged into 46 chromosomes (23 pairs) inside our cells.

The pairs numbered 1 to 22 are the same in males and females and are called autosomes. The 23rd pair are sex-determining chromosomes. Females have two Xs and males have one X and one Y.

Sperm and egg cells are different from other body cells. These reproductive cells each have only 23 unpaired chromosomes. When a single sperm and egg come together when pregnancy begins they form their own new cell with 46 chromosomes. The human being that results is genetically unique, with a blueprint half from each parent.

Gene Synthesis Gets Cheaper - 2

Well in our previous article we just saw how Gene Synthesis got cheaper...

just to round up on that a bit, i was eagerly looking at some ads that would show companies lookin at this technology.. for one we know that, world wide, Codon Devices gives 1bp at $0.79 !! that is like really low and based on what I've read about Codon Devices, they're pretty good.. also now we have a new contender for their title.. GenScript now is in with $0.75 per base pair!! Hey i'm not tryin to promote any brand here and I don't certainly make the news.. i just see em..

Looks like we have a price war starting..stay tuned for more!

Illumina, Solexa to merge

I know this is old stuff, but as usual the definative Gene Synthesis Blog brings u news that could impact the industry... read on...

SAN DIEGO—Illumina Inc. and Solexa Inc. announced in mid-November a definitive agree­ment under which Illumina will acquire Solexa in a stock-for-stock merger. Under the merger agreement, Solexa stockholders would receive Illumina common stock valued at $14 per share, for a total equity value of approxi­mately $600 million. Illumina also agreed to invest $50 million in Solexa in exchange for newly issued Solexa shares.
The merger announcement comes just months after Solexa began moving its next-generation sequencing platform, the 1G Genome Analyzer, to a handful of select customers and prepares to aggressively launch the product to the broader market in 2007. Furthermore, it joins together compa­nies that have plied the waters of both gene expression and gene sequencing, mar­kets that Illumina officials say are highly complementary and that it estimates in excess of $2.25 billion.
“For around the last 18 months, we and our CEO [Jay Flatley] have been looking at next-generation sequencing technolo­gies,” says John Stuelpnagel, COO of Illumina. “We knew that what we are doing in genotyping and gene expression had great overlap and synergies and that the tech­nologies could play off each other.”
Specifically, Illumina sees cross selling and integration opportuni­ties for researchers using Solexa’s 1G Genome Analyzer for whole-genome resequencing to use those results to conduct additional work on Illumina’s BeadStation for whole-genome genotyping. Likewise, results from the BeadStation for targeted genotyping studies could suggest additional work for target­ed resequencing appropriate for the 1G Genome Analyzer.
“This merger will create the only company today that can offer both analog and digital gene expression,” notes Stuelpnagel. “From Illumina’s standpoint, it was also an opportunity to bring in a sequencing technology that is much farther along than com­peting technologies and to rapidly commercialize it.”
For Solexa, the time to join with Illumina was suitable as it pre­pares to ramp up the production and marketing of its 1G product—a system it maintains has the poten­tial to generate “upwards to 1 bil­lion bases of data in a single run.” The company also says it can cur­rently sequence an entire genome for around $100,000, a figure that is orders of magnitude separated from its nearest competitor.
“We started talking with Illumina about a collaboration to help us with our sequencing tool,” says Omead Ostadan, VP of mar­keting for Solexa. “But as we con­tinued to talk, what we found was there was much more we could do as a company by merging with them both from a technology and a technical standpoint.”
While Solexa will benefit from Illumina’s large sales and support footprint in the global market, there are also opportunities for Illumina’s manufacturing infra­structure to help with the com­mercial ramp up of the 1G.
Still, Stuelpnagel notes, there is no intention of significantly chang­ing the operations at Solexa’s two operating centers in Hayward, Calif. and Cambridge, England.
When the merger is completed, expected in the first quarter of 2007, current Solexa CEO John West will stay on with the compa­ny as senior VP and general man­ger of the sequencing business.