Can Hobbyists and Hackers Transform Biotechnology?

For most of us, managing our health means visiting a doctor. The more serious our concerns, the more specialized a medical expert we seek. Our bodies often feel like foreign and frightening lands, and we are happy to let someone with an MD serve as our tour guide. For most of us, our own DNA never makes it onto our personal reading list.

Biohackers are on a mission to change all that. These do-it-yourself biology hobbyists want to bring biotechnology out of institutional labs and into our homes. Following in the footsteps of revolutionaries like Steve Jobs and Steve Wozniak, who built the first Apple computer in Jobs’s garage, and Sergey Brin and Larry Page, who invented Google in a friend’s garage, biohackers are attempting bold feats of genetic engineering, drug development, and biotech research in makeshift home laboratories.

In Biopunk, journalist Marcus Wohlsen surveys the rising tide of the biohacker movement, which has been made possible by a convergence of better and cheaper technologies. For a few hundred dollars, anyone can send some spit to a sequencing company and receive a complete DNA scan, and then use free software to analyze the results. Custom-made DNA can be mail-ordered off websites, and affordable biotech gear is available on Craigslist and eBay.

via Can Hobbyists and Hackers Transform Biotechnology? – Technology Review.

Newly Engineered Genetic Switches Enhance Production Of Proteins, Pharmaceuticals

Bacteria have evolved complex mechanisms called quorum sensing systems that provide for cell-to-cell communication, an adaptation that allows them to wait until their population grows large enough before mounting an attack on a host or competing for nutrients. Lianhong Sun, a chemical engineer at the University of Massachusetts Amherst, has engineered one of these systems to create genetic switches that could lower the cost of producing therapeutic proteins and pharmaceuticals.

Scientists Create the First Synthetic Bacterial Genome

A team of 17 researchers at the J. Craig Venter Institute (JCVI) has created the largest man-made DNA structure by synthesizing and assembling the 582,970 base pair genome of a bacterium, Mycoplasma genitalium JCVI-1.0. This work, published online today in the journal Science by Dan Gibson, Ph.D., et al, is the second of three key steps toward the team’s goal of creating a fully synthetic organism. In the next step, which is ongoing at the JCVI, the team will attempt to create a living bacterial cell based entirely on the synthetically made genome.

Researchers discover a gene that might control fat accumulation

Researchers at UT Southwestern Medical Center have found that a single gene might control whether or not individuals tend to pile on fat, a discovery that may point to new ways to fight obesity and diabetes.

“From worms to mammals, this gene controls fat formation,” said Dr. Jonathan Graff, associate professor of developmental biology and internal medicine at UT Southwestern and senior author of a study appearing in the Sept. 5 issue of Cell Metabolism. “It could explain why so many people struggle to lose weight and suggests an entirely new direction for developing medical treatments that address the current epidemic of diabetes and obesity.

“People who want to fit in their jeans might someday be able to overcome their genes.”

Scientists turn mouse into factory for human liver cells

Oregon Health & Science University researchers have figured out how to turn a mouse into a factory for human liver cells that can be used to test how pharmaceuticals are metabolized.

The technique, published in the journal Nature Biotechnology, could soon become the gold standard not only for examining drug metabolism in the liver, which helps scientists determine a drug’s toxicity. But it also can be used as a platform for testing new therapies against infectious diseases that attack the liver, such as hepatitis C and malaria.

Bioengineers Devise ‘Dimmer Swith’ To Regulate Gene Expression In Mammal Cells

Three Boston University biomedical engineers have created a genetic dimmer switch that can be used to turn on, shut off, or partially activate a gene’s function. Professor James Collins, Professor Charles Cantor and doctoral candidate Tara Deans invented the switch, which can be tuned to produce large or small quantities of protein, or none at all

This switch helps advance the field of synthetic biology, which rests on the premise that complex biological systems can be built by arranging components or standard parts, as an electrician would to build an electric light switch. Much work in the field to date uses bacteria or yeast, but the Boston University team used more complex mammalian cells, from hamsters and mice. The switch has several new design features that extend possible applications into areas from basic research to gene therapy.

Mutating the entire genome

Genes account for only 2.5 percent of DNA in the human genetic blueprint, yet diseases can result not only from mutant genes, but from mutations of other DNA that controls genes. University of Utah researchers report in the journal Nature Genetics that they have developed a faster, less expensive technique for mutating those large, non-gene stretches of DNA.

 

 

 

Scientists develop a general ‘control switch’ for protein activity

Prof. Mordechai “Moti” Liscovitch and graduate student Oran Erster of the Weizmann Institute’s Biological Regulation Department, have recently developed a unique “switch” that can control the activity of any protein, raising it several-fold or stopping it almost completely. The method provides researchers with a simple and effective tool for exploring the function of unknown proteins, and in the future the new technique may find many additional uses.

The switch has a genetic component and a chemical component: Using genetic engineering, the scientists insert a short segment of amino acids into the amino acid sequence making up the protein. This segment is capable of binding strongly and selectively to a particular chemical drug, which affects the activity level of the engineered protein by increasing or reducing it. When the drug is no longer applied, or when it is removed from the system, the protein returns to its natural activity level.

Scientists create mice with enhanced color vision

Researchers at the Johns Hopkins School of Medicine and their colleagues have found that mice simply expressing a human light receptor in addition to their own can acquire new color vision, a sign that the brain can adapt far more rapidly to new sensory information than anticipated.

This work, appearing March 23 in Science, also suggests that when the first ancestral primate inherited a new type of photoreceptor more than 40 million years ago, it probably experienced immediate color enhancement, which may have allowed this trait to spread quickly.

The Incredible, Medical Egg

Genetically modified chickens that produce medicines in their eggs may be the drug factories of the future. The chicken egg has a storied history in medicine. Even today, millions of ordinary fertilized eggs are each punctured with a drill and injected with flu virus to make vaccines. Now, scientists at the same research institute that cloned Dolly the sheep have produced a genetically modified rooster whose female descendants lay eggs that produce medicines in place of a protein in egg whites.

Helen Sang of the Roslin Institute in Edinburgh, Scotland, and her colleagues used lentivirus to introduce a gene into freshly fertilized chicken embryos that trigger the production of various drugs rather than the protein ovalbumin, which normally makes up roughly 54 percent of egg whites. The researchers screened the resultant cockerels for one that produced the new gene in its semen. They then bred him with normal hens to produce a flock of chickens that carried the inserted gene thereby producing medicines in their egg’s whites.

Read rest of the story at Scientific American

‘Marathon mice’ elucidate little-known muscle type

Researchers report in the January issue of the journal Cell Metabolism, published by Cell Press, the discovery of a genetic “switch” that drives the formation of a poorly understood type of muscle. Moreover, they found, animals whose muscles were full of the so-called IIX fibers were able to run farther and at higher work loads than normal mice could.

The findings could ultimately lead to novel drugs designed to change the composition of muscle, the researchers said. Such treatments might have the potential to boost physical strength and endurance in patients with a variety of muscle wasting conditions.

A Better Artificial Skin

A patient’s skin cells, genetically modified and grown in a test tube, could provide the next generation of artificial skin. As a first step in creating such replacement skin, scientists in Cincinnati have engineered bacteria-resistant skin cells in the lab and are now testing them in animals. Ultimately, they hope to produce a type of artificial skin that can sweat, tan, and fight off infection.

“We’re using genetic modification to try to get the cultured skin to behave more like normal skin,” says Dorothy Supp, a researcher at the Cincinnati Shriners Hospital for Children who led the project.

Read rest of the story at Technology Review

Buildup of damaged DNA in cells drives aging

The accumulation of genetic damage in our cells is a major contributor to how we age, according to a study being published today in the journal Nature by an international group of researchers. The study found that mice completely lacking a critical gene for repairing damaged DNA grow old rapidly and have physical, genetic and hormonal profiles very similar to mice that grow old naturally. Furthermore, the premature aging symptoms of the mice led to the discovery of a new type of human progeria, a rare inherited disease in which affected individuals age rapidly and die prematurely.

A new mechanism of aging discovered

We all age, it’s a fact of life, like death and taxes, and there’s nothing we can do about it. But, how is it possible that of two middle-aged mice, one is already grey, balding and frail? Some mice that age three times faster than normal are revealing to scientists why we grow old.

Researchers have discovered that genetic mutations in the powerhouses of our cells — mitochondria — appear to trigger cells to die and speed up the aging process. Inducing these kinds of mitochondrial mutations leads to premature aging in mice, which live only about half as long as normal mice.

Jumping gene could provide non-viral alternative for gene therapy

A jumping gene first identified in a cabbage-eating moth may one day provide a safer, target-specific alternative to viruses for gene therapy, researchers say.

They compared the ability of the four best-characterized jumping genes, or transposons, to insert themselves into a cell’s DNA and produce a desired change, such as making the cell resistant to damage from radiation therapy.

They found the piggyBac transposon was five to 10 times better than the other circular pieces of DNA at making a home and a difference in several mammalian cell lines, including three human ones.

Scientists find boosting protein levels staves off heart failure

Boosting levels of a protein in the heart might help protect against the development of heart failure, particularly in those who have had heart attacks.

Cardiology researchers at the Center for Translational Medicine at Jefferson Medical College of Thomas Jefferson University in Philadelphia found that increasing levels of the protein S100A1 above normal helped protect animal hearts from further damage after simulated heart attacks. In some cases, the animals’ heart function hardly changed at all. At the same time, other animals with heart cells lacking the gene for the protein couldn’t handle the stress of a heart blockage; they went on to develop heart failure.

Researchers genetically transform immune cells into tumor fighters

A team of researchers has genetically engineered normal immune cells to become specialized tumor fighters, demonstrating for the first time that these engineered cells can persist in the body and shrink large tumors in humans.

Family Of Life-extending Genes Discovered

Mice, rats, worms, flies, and yeast all live longer on a low-calorie diet, which also seems to protect mammals against cancer and other aging-related diseases. A gene called SIR2 is thought to control this process. Now, researchers at Harvard Medical School and UC Davis have discovered four cousins of the SIR2 gene that also extend lifespan, suggesting that the whole family of SIR2 genes is involved in controlling lifespan. The research indicates potential targets for developing drugs to lengthen life and prevent or treat aging-related diseases. The findings are reported July 28 in the advance online edition of Science. This discovery comes on the heels of the Harvard group’s discovery of a molecule in red wine that extends the lifespan of every organism so far tested.

Sperm created in the laboratory from embryonic stem cells produce viable progeny

Scientists have demonstrated for the first time that embryonic stem (ES) cells cultured in the laboratory can produce sperm with the capacity to produce viable offspring. The research, published in the July issue of Developmental Cell, opens many exciting avenues for future studies, including investigation of mechanisms involved in sperm production and development of new treatment strategies for infertility.

The aging-clock connection

In the July 15th issue of G&D, Dr. Marina Antoch and colleagues (The Lerner Research Institute) establish a link between the innate biological clock – known as the circadian clock – and aging.

Research Identifies Protein In Mice That Regulates Bone Formation

Osteoporosis, a disease characterized by a decrease in bone mass and density and which makes people more susceptible to bone fractures and deformities, afflicts some 10 million Americans over the age of 50. Researchers at the Harvard School of Public Health (HSPH) have discovered that eliminating a protein, Schnurri-3 (Shn3), in mice led to profound increases in bone mass throughout their skeletal system. The results may have implications for the treatment of osteoporosis. The study was published in the May 26 edition of Science.

A Key Regulator Of Fat Synthesis Keeps Mice Lean Despite A High-fat Diet

Scientists at the Salk Institute for Biological Studies have identified a novel pathway that regulates the body's ability to store or burn fat, a discovery that suggests new ways to reduce obesity, diabetes and other fat-related human diseases.

Genetically engineered mice, in which the pathway was constantly revved up, were protected from the ravages of a high-fat diet, the Salk team led by Marc Montminy, Ph.D., a professor in the Clayton Foundation Laboratories for Peptide Biology reports in this week's issue of Science.

Reprogramming Biology

Visionary futurist Ray Kurzweil, whose remarkable ideas on technological progress have been an inspiration for Biosingularity blogs, have a wonderful concise article on biological advances in recent issue of Scientific American. 

As a scientist working on biological systems I fully agree and whole heartedly support Kurzweil's observations that: " Biology is now in the early stages of an historic transition to an information science, while also gaining the tools to reprogram the ancient information systems of life ….. We are now beginning to understand biology as a set of information processes, and we're developing realistic models and simulations of how the processes involved in disease and aging progress. Moreover, we are developing the tools to reprogram them."

In the article Kurzweil predicts that tinkering with our genetic programs will extend human lifespan beyond the current limits. He also reiterates that biological systems are also subject to the "law of accelerating returns", which had tremendous impact on information technologies. Indeed, the cost of sequencing and synthesizing gene base pairs have decreased more than 10,000 fold over the last 15 years, and this exponential progress is currently accelerating as predicted by Kurzweil in his recent book. 

Read rest of the article at Scientific American web site.
 

Selenium-protein deficiency raises prostate cancer risk

Selenium, an essential dietary mineral that can act as an antioxidant when incorporated into proteins, has been shown in many studies to reduce the incidence of cancers — notably lung, colorectal and prostate.

Alan Diamond, professor of human nutrition at the University of Illinois at Chicago, and his colleagues report in the May 23 issue of the Proceedings of the National Academy of Sciences on research findings using specially bred transgenic mice that suggest it is the level of selenium-containing proteins in the body that is instrumental in preventing cancer, and that dietary selenium plays a role in stimulating the body's level of these selenoproteins.

Mice Lacking Key Immune Component Still Control Chronic Viral Infections

Despite lack of a key component of the immune system, a line of genetically engineered mice can control chronic herpes virus infections, researchers at Washington University School of Medicine in St. Louis have found.

Scientists can't prove it yet, but they suspect the missing immune system component, a group of molecules known as the Major Histocompatibility Complex (MHC) Class Ia, has a previously unrecognized backup that is similar enough to step in and fill the void left by its absence. If so, that backup may become a new focus for efforts to design antiviral vaccines.

Making Mice Old Before Their Time

Knocking out a gene that helps repair nicks in DNA causes young mice to develop many of the degenerative characteristics of their wizened elders. Mice lacking the gene develop hunchback, thinning skin, decreasing bone density, and a declining immune system — all in the span of a month.

The researchers do not know whether the accelerated aging-like effects of losing the gene, called SIRT6, relate to its role in DNA repair. Nor do they know whether the degenerative effects are relevant to the natural aging process. However, they said, the discovery offers an intriguing new model for studying DNA repair, as well as its possible role in aging-related degeneration.

Researchers develop all-in-one remote control gene expression tool derived from HIV

In an article appearing online today in the journal Nature Methods, researchers at the EPFL (Ecole Polytechnique Fédérale de Lausanne) unveil a powerful new tool that will facilitate genetic research and open up new avenues for the clinical treatment of genetic disease.

An all-in-one tool like this – efficiently combining techniques that each previously required separate delivery – will likely see wide use in genetic research and in clinical gene therapy applications. It is particularly applicable for use in stem cells, embryonic cells and tissues and organs that are amenable to genetic transduction.

Rare breast stem cell drives formation of breast tissue and may also lead to tumours

Scientists from The Walter and Eliza Hall Institute, using a mouse model, have discovered the rare stem cell that drives the formation of all breast tissue. This discovery lays an important foundation for understanding how normal breast tissue develops. The identification of the breast stem cell is also likely to provide clues about how breast cancer develops and how rogue cells evade current therapies.

Scientists discover a protein linked to serotonin and depression

For the more than 18 million Americans who suffer from depressive illnesses, the best pharmacological treatments are those that increase levels of serotonin, the brain chemical that regulates mood, sleep and memory. New research by an international team of scientists, led by Rockefeller University researchers in Nobel prize winner Paul Greengard’s laboratory, shows that a gene called p11 is closely related to serotonin transmission in the brain — and may play a key role in determining a person’s susceptibility to depression.

The newly discovered link between depression and the serotonin system, reported in the January 6 issue of the journal Science, could lead to new treatments for these mental disorders.

First synthetic biology company is launched

Synthetic Genomics, Inc., a company founded by the genome sequencing pioneer Dr. J. Craig Venter, is developing new scientific processes to enable industry to design and test desired genetic modifications. Using the genome as a bio-factory, a custom designed, modular “cassette” system will be developed so that the organism executes specific molecular functions. Synthetically produced organisms with reduced or reoriented metabolic needs will enable new, powerful, and more direct methods of bio-engineered industrial production.

According to Dr. Venter: “Work in creating a synthetic chromosome/genome will give us a better understanding of basic cellular processes. Genome composition, regulatory circuits, signaling pathways and numerous other aspects of organism gene and protein function will be better understood through construction of a synthetic genome. Not only will this basic research lead to better understanding of these pathways and components in the particular organisms, but also better understanding of human biology. The ability to construct synthetic genomes may lead to extraordinary advances in our ability to engineer microorganisms for many vital energy and environmental purposes.”

This is a very exciting new step towards biosingularity. Dr. Venter is a true visionary who has been relentlessly pushing the technology to decode the complex program of biological systems.

Role of p53 inhibitor in tumor suppression and aging

The p53 tumor suppressor plays a critical role in cancer formation, and many anticancer strategies aim to activate p53 in order to curb tumor formation. Mdm2 is a key inhibitor of p53 and therefore an attractive target to modulate p53 activity in cells. However, conflicting evidence exists regarding whether or not p53-mediated tumor suppression comes at the cost of accelerated aging.

In the January 1 issue of Genes & Development, Dr. Mary Ellen Perry and colleagues validate the p53 inhibitor, Mdm2, as a promising target for cancer therapies.

Study suggests way to re-energize immune response to chronic viral infection

Like boxers wearied by a 15-round bout, the immune system’s CD8 T cells eventually become “exhausted” in their battle against persistent viral infection, and less effective in fighting the disease.

In a study to be published Dec. 28 on the journal Nature’s website, researchers at Dana-Farber Cancer Institute and Emory University have traced the problem to a gene that turns off the infection-fighting drive of CD8 T cells in mice. The discovery raises the possibility that CD8 cell exhaustion can be reversed in human patients, reinvigorating the immune system’s defenses against chronic viral infections ranging from hepatitis to HIV, the virus that causes AIDS.

Researchers discover how a high-fat diet causes type 2 diabetes

Howard Hughes Medical Institute researchers have discovered a molecular link between a high-fat, Western-style diet, and the onset of type 2 diabetes. In studies in mice, the scientists showed that a high-fat diet disrupts insulin production, resulting in the classic signs of type 2 diabetes.

In an article published in the December 29, 2005, issue of the journal Cell, the researchers report that knocking out a single gene encoding the enzyme GnT-4a glycosyltransferase (GnT-4a ) disrupts insulin production. Importantly, the scientists showed that a high-fat diet suppresses the activity of GnT-4a and leads to type 2 diabetes due to failure of the pancreatic beta cells.

Sickle cell disease corrected in human models using stem cell-based gene therapy

In a study to be published in the January 2006 issue of Nature Biotechnology, researchers led by a team of scientists at Memorial Sloan-Kettering Cancer Center have devised a novel strategy that uses stem cell-based gene therapy and RNA interference to genetically reverse sickle cell disease (SCD) in human cells. This research is the first to demonstrate a way to genetically correct this debilitating blood disease using RNA interference technology.

Scientists Discover a Gene That Regulates Lifespan

Genes that control the timing of organ formation during development also control timing of aging and death, and provide evidence of a biological timing mechanism for aging, Yale researchers report in the journal Science.

“Although there is a large variation in lifespan from species to species, there are genetic aspects to the processes of development and aging,” said Frank Slack, associate professor of Molecular, Cellular and Developmental Biology and senior author of the paper. “We used the simple, but genetically well-studied, C. elegans worm and found genes that are directly involved in determination of lifespan. Humans have genes that are nearly identical.”

Researchers hone in on differentiation of heart stem cells

A team of scientists from the Gladstone Institute of Cardiovascular Disease (GICD) has identified a key factor in heart development that could help advance gene therapy for treating cardiac disorders.

The findings could help cardiac stem cell researchers one day develop strategies for gene and cell- mediated cardiac therapies.

Creating first synthetic life form

Work on the world’s first human-made species is well under way at a research complex in Rockville, Md., and scientists in Canada have been quietly conducting experiments to help bring such a creature to life.

Robert Holt, head of sequencing for the Genome Science Centre at the University of British Columbia, is leading efforts at his Vancouver lab to play a key role in the production of the first synthetic life form — a microbe made from scratch.

The project is being spearheaded by U.S. scientist Craig Venter, who gained fame in his former job as head of Celera Genomics, which completed a privately-owned map of the human genome in 2000.

A Little Telomerase Isn’t Enough: Study Links Length Of Chromosome Ends To A Rare Disease Of Stem Cells

Chromosome ends, or telomeres, are repetitive stretches of DNA that protect chromosomes in much the same way as plastic tips on shoelaces prevent the fabric from fraying. Each time a cell divides, its chromosome ends get a little shorter, and eventually the cell can no longer divide because its critical genetic information is exposed. In stem cells, however, a protein called telomerase normally maintains the telomeres’ length, allowing the cells to divide indefinitely.

Now, the Hopkins researchers report that mice engineered to have just half the normal amount of telomerase can’t maintain their stem cells’ chromosome ends, showing that a little telomerase isn’t enough. In these “half-telomerase” mice, their telomeres shortened over time, bringing an early demise to stem cells that replenish the blood supply, immune system and intestine, the researchers report. Moreover, offspring of these mice bred to have normal levels of telomerase still exhibited early loss of stem cells, the researchers report in the Dec. 16 issue of Cell.

Cancer Support Cells May Evolve, Fuel Tumor Growth, Study Shows

University of North Carolina at Chapel Hill scientists have demonstrated in a living organism that cancers may cause surrounding supportive cells to evolve and ultimately promote cancer growth.

The new research offers what is believed to be the first evidence that mutations within cancer cells can signal surrounding tissue cells to alter their molecular composition in ways that promote tumor growth and proliferation. Moreover, the findings also suggest that cell mutations that promote cancer progression may arise in cells other than the predominant cancer cell.

Lower levels of Cancer-suppressing Protein Increase Life Span

Fruit flies can live significantly longer, and remain healthy, when activity of the fly version of the tumor-suppressing protein p53 is reduced in nerve cells. Published in Current Biology, the results shed important new light on the role this “protector of the genome” plays in aging and point to p53 as a viable target for anti-aging drugs.

The p53 gene plays a critical role in the body. It protects human cells by producing a protein that triggers apoptosis, or cell suicide, when DNA is badly damaged. This prevents the spread of genetic mutations and the formation of cancer. When the p53 gene is damaged or missing, cancer may result. In fact, more than 50 percent of human cancers carry p53 mutations.

New technique multiplies life span in simple organisms

A counterintuitive experiment has resulted in one of the longest recorded life-span extensions in any organism and opened a new door for anti-aging research in humans.

Scientists have known for several years that an extra copy of the SIR2 gene can promote longevity in yeast, worms and fruit flies. That finding was covered widely and incorporated into anti-aging drug development programs at several biotechnology companies. Now, molecular geneticists at the University of Southern California suggest that SIR2 instead promotes aging.

Hair follicle stem cells contribute to wound healing

Hair follicle stem cells are important contributors to the wound-healing process, according to new research by investigators at the University of Pennsylvania School of Medicine. Using an animal model, the researchers discovered that stem cells in the hair follicle are enlisted to help heal wounds in the skin. This finding, may suggest a therapeutic target for the development of drugs to encourage and promote wound healing.

Genetically engineered mice have no fear!

Could this explain what gave cartoon hero Mighty Mouse the courage to fight evil? Researchers have found that flesh-and-blood mice lacking a particular gene are unusually brazen, venturing into wide open spaces and onto narrow bridges that their genetically normal kin avoid. The mutant mice also appear to have weaker memories of scary encounters than normal mice do.