Synthetic Biology and Gene Synthesis

Types of Stem Cells

2012-01-04T06:55:00.000-08:00

A brief look at the different types of Stem Cells and their comparisons. You can click on the image for a larger view

The ISSCR has published a large list of the various TYPES of stem cells, and it warrants a closer look at them to develop a deeper understanding of what they are.

1. Adult Stem Cells or Tissue-specific Stem Cells

Many adult tissues contain stem cells that can replace cells that die or restore tissue after injury. Skin, muscle, intestine and bone marrow, for example, each contain their own stem cells. In the bone marrow, billions of new blood cells are made every day from blood-forming stem cells.
Adult stem cells are tissue-specific, meaning they are found in a given tissue in our bodies and generate the mature cell types within that particular tissue or organ. It is not clear whether all organs, such as the heart, contain stem cells. The term ‘adult stem cells’ is often used very broadly and may include fetal and cord blood stem cells.
There are a few stem cell therapies that are widely accepted by the medical community and these use tissue-specific stem cells. These are bone marrow or cord blood stem cell transplantation to treat diseases and conditions of the blood or to restore the blood system after treatment for specific cancers, skin stem cell therapies for burns and limbal stem cells for corneal replacement. In each case, the stem cells repair the same tissue from which they came.
Another type of adult stem cell is the mesenchymal stem cell. These are found in a number of tissues, including bone marrow, and may be able to produce bone, cartilage and fat. It is also possible that these or similar cells may aid in the regeneration of tissues. Extensive animal studies are currently ongoing to determine if these cells may be used for treatment of diseases such as arthritis and non-healing bone fractures. It is also possible that these or similar cells modulate the immune system in response to injury.

2. Fetal Stem Cells

As their name suggests, fetal stem cells are taken from the fetus. The developing baby is referred to as a fetus from approximately 10 weeks of gestation. Most tissues in a fetus contain stem cells that drive the rapid growth and development of the organs. Like adult stem cells, fetal stem cells are generally tissue-specific, and generate the mature cell types within the particular tissue or organ in which they are found.

3. Cord Blood Stem Cells

At birth the blood in the umbilical cord is rich in blood-forming stem cells. The applications of cord blood are similar to those of adult bone marrow and are currently used to treat diseases and conditions of the blood or to restore the blood system after treatment for specific cancers. Like the stem cells in adult bone marrow, cord blood stem cells are tissue-specific.

4. Embryonic Stem Cells

Embryonic stem cells are derived from very early embryos and can in theory give rise to all cell types in the body. However, coaxing these cells to become a particular cell type in the laboratory is not trivial. Furthermore, embryonic stem cells carry the risk of transforming into cancerous tissue after transplantation. To be used in cell transplant treatments the cells will most likely need to be directed into a more mature cell type, both to be therapeutically effective and to minimize risk that cancers develop. While these cells are already helping us better understand diseases and hold enormous promise for future therapies, there are currently no treatments using embryonic stem cells accepted by the medical community.

5. Induced Pluripotent Stem Cells (iPS cells)

In 2006, scientists discovered how to “reprogram” cells with a specialized function (for example, skin cells) in the laboratory, so that they behave like an embryonic stem cell. These cells, called induced pluripotent cells or iPS cells, are created by inducing the specialized cells to express genes that are normally made in embryonic stem cells and that control how the cell functions. Embryonic stem cells and iPS cells share many characteristics, including the ability become the cells of all organs and tissues, but they are not identical and can sometimes behave slightly differently. IPS cells are a powerful method for creating patient- and disease-specific cell lines for research. However, the techniques used to make them need to be carefully refined before they can be used to generate iPS cells suitable for safe and effective therapies.

What are stem cells and why are they important?

2012-01-02T06:51:00.000-08:00

Stem cells have two important characteristics that distinguish them from other types of cells.
First, they are unspecialized cells that renew themselves for long periods through cell division. The second is that under certain physiologic or experimental conditions, they can be induced to become cells with special functions such as the beating cells of the heart muscle or the insulin producing cells of the pancreas.

Scientists primarily work with two kinds of stem cells from animals and humans: embryonic stem cells and adult stem cells, which have different functions and characteristics that will be explained in this document. Scientists discovered ways to obtain or derive stem cells from early mouse embryos more than 20 years ago. Many years of detailed study of the biology of mouse stem cells led to the discovery, in
Stem Cell Information

Many years of detailed study of the biology of mouse stem cells led to the discovery, in 1998, of how to isolate stem cells from human embryos and grow the cells in the laboratory. These are called human embryonic stem cells. The embryos used in these studies were created for infertility purposes through in vitro fertilization procedures and when they were no longer needed for that purpose, they were donated for research with the informed consent of the donor.

Stem cells are important for living organisms for many reasons. In the 3- to 5-day-old embryo, called
a blastocyst, stem cells in developing tissues give rise to the multiple specialized cell types that make
up the heart, lung, skin, and other tissues. In some adult tissues, such as bone marrow, muscle, and
brain, discrete populations of adult stem cells generate replacements for cells that are lost through
normal wear and tear, injury, or disease.

It has been hypothesized by scientists that stem cells may, at some point in the future, become the basis
for treating diseases such as Parkinson's disease, diabetes, and heart disease. Scientists want to study stem cells in the laboratory so they can learn about their essential properties and what makes them different from specialized cell types. As scientists learn more about stem cells, it may become possible to use the cells not just in cell-based therapies, but also for screening new drugs and toxins and understanding birth defects.

However, as mentioned above, human embryonic stem cells have only been studied since 1998. Therefore, in order to develop such treatments scientists are intensively studying the fundamental properties of stem cells, which include:
1. determining precisely how stem cells remain unspecialized and self renewing for many years;
and
2. identifying the signals that cause stem cells to become specialized cells.

The International Society for Stem Cell Research lists out several types of Stem Cells. Look for that in our next post.

Source: National Institutes of Health

Stem Cells - The Basics

2012-01-01T00:00:00.000-08:00

Stem cells have the remarkable potential to develop into many different cell types in the body. Serving as a sort of repair system for the body, they can theoretically divide without limit to replenish other cells as long as the person or animal is still alive. When a stem cell divides, each new cell has the potential to either remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell.

Research on stem cells is advancing knowledge about how an organism develops from a single cell and
how healthy cells replace damaged cells in adult organisms. This promising area of science is also
leading scientists to investigate the possibility of cell-based therapies to treat disease, which is often
referred to as regenerative or reparative medicine.

Stem cells are one of the most fascinating areas of biology today. But like many expanding fields of
scientific inquiry, research on stem cells raises scientific questions as rapidly as it generates new
discoveries.

We will take you dear readers through various topics related to Stem Cells to understand the answers to questions such as:
What are stem cells?
What different types of stem cells are there and where do they come from?
What is the potential for new medical treatments using stem cells?
What research is needed to make such treatments a reality?

Source: http://stemcells.nih.gov

Stem Cells and Everything you need to know

2011-12-31T00:00:00.000-08:00

Dear Friends and Readers.

I've received several emails asking the blog to cover Stem Cells and it's uses and purposes. Over next few weeks, we'll be dedicating this section to All things Stem Cells related.

I also want to take this opportunity to thank you for your support on this blog and post taking it over in November 2011, I promise to take it to new levels and continue it's purpose of sharing and collaborating information regarding Synthetic Biology and Gene Synthesis.

Wishing everyone a Very very happy NEW YEAR!!

Thank You,
Morgan.

Hillary Clinton warns of gene assembly's ability to create bioweapons

2011-12-29T19:53:00.000-08:00

U.S. Secretary of State Hillary Clinton recently warned that gene assembly technology research could potentially be used by terrorists to create biological weapons. If this is 'a' possible future or not, only time will tell, however it is indeed a scary thought.

The threat from bioweapons has drawn little attention in recent years, as governments focused more on the risk of nuclear weapons proliferation to countries such as Iran and North Korea.
But experts have warned that the increasing ease with which bioweapons can be created might be used by terror groups to develop and spread new diseases that could mimic the effects of the fictional global epidemic portrayed in the Hollywood thriller "Contagion."

Many have been calling on the elimination of current viruses and diseases that, if in the wrong hands, could be a powerful weapon. The U.S. announced plans to destroy their smallpox stockpile in May 2011, despite protests from the public. The government feared that terrorists could use the virus to unleash a devastating attack. The disease, which killed one-third of those who were infected, was last seen in 1978.
As late as 2010, a congressional mandated panel reported that the U.S. would not be prepared for a bioweapon attack. The Commission on the Prevention of Weapons of Mass Destruction Proliferation said the Obama administration failed in its efforts to prepare for and respond to a biological attack, such as the release of deadly viruses or bacteria. After that report, Obama announced during his State of the Union speech that the country would be making strides to make sure it was prepared for a biological terrorist attack scenario.

The World Health Organization (WHO) has been pushing for countries to eliminate their stockpiles since 2006. However, at the WHO's annual meeting, it was decided that nations' could keep their smallpox stockpiles for at least another three more years in order to develop vaccines and anti-virals, according to Reuters.

"The emerging gene synthesis industry is making genetic material more widely available," she said. "This has many benefits for research, but it could also potentially be used to assemble the components of a deadly organism."

This probably reminds people about the Anthrax attacks almost a decade ago. Washington has urged countries to increase transparency in their effort to lower the threat of bioweapons, but U.S. officials have shied away from calling for a formal international verification system, citing the complications that would be involved in monitoring the vast number of labs that would have to be monitored.

Genes Predict Mesothelioma Treatment Response

2011-12-29T19:48:00.000-08:00

Mesothelioma is a fast-growing cancer triggered by exposure to asbestos. It is often treated with multiple modalities, including chemotherapy. As more is understood about the impact of genetics on medication response, chemotherapy for cancers like mesothelioma is moving away from a ‘one-size-fits-all’ approach to a more tailored approach based on individual cellular characteristics.

University of Chicago researchers have released the results of genetic studies they hope will shed some light on why some mesothelioma patients respond well to pemetrexed (Alimta) while others do not.

This is a copyrighted article hence cannot publish the entire thing here. But for more information on this you can visit the site at http://www.survivingmesothelioma.com/

Stem cell cure for hearing loss in aged

2011-12-29T17:56:00.000-08:00

In a first of its kind study, a team of scientists in the UK have tried to "grow" new stem cells in the ear that get damaged with age, a finding they say could help combat hearing loss associated with old-age.

Researchers at Keele University found that in some cases hearing begins to decline when fibrocytes - cells in the inner ear - start to degenerate with age.

Once these cells die and don't function correctly, other parts of the inner ear can become permanently damaged, leading to increased loss of hearing and possible deafness, said the researchers. Dr Dave Furness and his team have begun research which will explore whether replacement fibrocytes and fibrocyte stem cells can be successfully grown and implanted into the ear.

If successful, the research could pave the way towards the prevention of age related hearing loss, Furness said. "We set out to explore why deafness occurs as a result of aging and what we discovered was that fibrocytes, the part of the ear involved in managing fluid composition in the cochlea, do degrade due to old age," Furness said.

Once this happens, he said, it causes hearing sensitivity to decrease.

breaking news at times of india.

Today's lifestyles, tomorrow's cancers: trends in lifestyle risk factors for cancer in low- and middle-income countries

2011-10-25T20:13:00.000-07:00

Abstract

Background: The global burden of cancer is projected to increase from 13.3 to 21.4 million incident cases between 2010 and 2030 due to demographic changes alone, dominated by a growing burden in low- and middle-income countries (LMICs). Lifestyle risk factors for cancer are also changing in these countries and may further influence this burden.

Design: We consider examples of changes already occurring in population-level distributions of tobacco and alcohol consumption, body weight, and reproductive lives of women to gauge the magnitude of their projected impact on cancer incidence in future decades.

Results: Trends in lifestyle factors vary greatly between settings and by sex. Some common trends point to considerable increases in cancers of the (i) lung in men due to tobacco smoking; (ii) upper aerodigestive tract (UADT) due to increasing tobacco and alcohol consumption, worse in men; (iii) colon from increasing body mass index, and alcohol and tobacco consumption; and (iv) in women, breast due particularly to consistent international trends of younger age at menarche, smaller family size, and, at postmenopausal ages, increasing body weight.

Conclusions: In many LMICs, the future cancer burden will be worsened by changing lifestyles. Affected common cancer sites likely to experience the largest increases are lung, colon, UADT, and breast.

read the full article here

even better

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Existing Technique Can Detect Fetal Genetic Abnormalities in Maternal Blood

2011-10-25T20:07:00.000-07:00

Non-invasive procedure could make prenatal testing easier, but it comes with ethical problems.

Until last week, scrutinizing a fetus's DNA for indications of genetic abnormalities meant tapping into the mother's womb with a needle. Now there's a test that can do it using a small sample of the mother's blood. MaterniT21, a Down's syndrome test that Sequenom of San Diego, California, launched in major centres across the United States on 17 October, is the first of several such tests expected on the market in the next year. It signals the arrival of a long-anticipated era of non-invasive prenatal genetic screening, with its attendant benefits and ethical complications.

With the technology in place to sequence the fetal DNA carried in a pregnant woman's bloodstream, geneticists predict the list of conditions that can be detected by non-invasive means will grow rapidly. Another company, Gene Security Network of Redwood City, California, says its forthcoming test will also check for other genetic abnormalities, and Sequenom is studying the feasibility of expanding its test.

"There's every reason to think that in the future you'll be able to extract an enormous amount of information from that sequencing data," says Peter Benn, director of the Diagnostic Human Genetics Laboratories at the University of Connecticut Health Center in Farmington.

Sequenom's test sequences 36-base-pair fragments of DNA to identify sections from chromosome 21. Normally, the chromosome contributes 1.35% of the total maternal and fetal DNA in the mother's blood. An overabundance of this material indicates the genetic abnormality that marks Down's syndrome.

Sequenom is marketing its test as an add-on to current screening methods, which estimate the chance that a woman is carrying a fetus with Down's syndrome from ultrasound results and protein markers in the blood. Such non-genetic screening can detect 90–95% of Down's syndrome cases, but falsely indicates that up to 5% of women are carrying a baby affected by the condition. Sequenom's test could be taken after a positive screening result to help a woman decide whether to undergo amniocentesis, a test that extracts amniotic fluid with a needle and carries a small risk of miscarriage. A study published this month, and paid for by Sequenom, found that the company's test has a false positive rate of 0.2% (G. E. Palomaki et al. Genet. Med. http://dx.doi.org/10.1097/GIM.0b013e3182368a0e; 2011).

It could spare some women from having amniocentesis after a false-positive screening result. But Benn says that the test will also pose difficulties. For instance, because it would take 8–10 days to get the results of Sequenom's test, if a woman did still opt for amniocentesis, and the result confirms that the baby has Down's syndrome, there would be little time left to decide whether to terminate the pregnancy. And some women who test positive on MaterniT21 will probably choose to terminate pregnancies immediately rather than have amniocentesis.

"Inserting this new test in the way that Sequenom is proposing is very difficult, from the patient perspective, and difficult for physicians and counsellors to manage," Benn says.

Ethicists also caution that using such easy screening methods ever earlier in pregnancy might worsen the gender imbalance seen in countries such as China and India. And if it becomes routine to check for many different kinds of genetic abnormalities, ethicists predict that more couples may face the quandary of whether to carry an 'unhealthy' fetus to term.

"The idea that couples have choices about whether to continue their pregnancies may become strained because parents may be seen as irresponsible for allowing 'defective' pregnancies to go to term," says Mildred Cho, an ethicist at Stanford University in Palo Alto, California. Other ethicists worry that fears of eugenics will be raised if testing can be done for less-serious conditions.

Sequenom is solely focused on developing tests for conditions that are already part of prenatal screening programmes, says Mathias Ehrich, the company's senior director for research and development diagnostics. "We do not want to invent new applications. Our focus is on making existing clinical applications safer," he says. "I don't think that we are in a position to say that we should determine what hair colour the baby has."

Cell therapy fights leukaemia

2011-09-01T23:03:00.000-07:00

It vindicates the cancer researchers who believe that cells are very smart drugs.

Two weeks after receiving an experimental treatment for his cancer, David Porter's 65-year-old leukaemia patient seemed to take a turn for the worse. Fatigue and fever drove the patient back to hospital, where his temperature surged to more than 39º C and he began to shake, his body racked with nausea and diarrhoea.

But rather than being a clinical failure, the patient's return to hospital heralded the treatment's success. His symptoms were the dying scream of more than a kilogram of leukaemia cells under attack by genetically engineered immune cells called T cells that Porter, an oncologist at the University of Pennsylvania Medical Center in Philadelphia, and his colleagues had infused two weeks earlier. As the T cells destroyed their targets, the sheer volume of cellular debris temporarily overwhelmed the patient's body.

Cells may be smart, but researchers have struggled to harness that intelligence to fight cancer. Early attempts to engineer T cells with chimeric antigen receptors failed to coax the cells to proliferate in the body. As a result, the modified cells soon died off, leaving little impact on the disease.

Porter's group is one the first to report results from a generation of chimeric receptors that include both an antibody to target the cancer and part of a receptor that amplifies the T-cell response. This time, the doctored T cells proliferated more than 1,000-fold in the body, and were still present at high levels six months after the treatment.

June credits this expansion and persistence for the study's dramatic results: two patients in complete remission and a third showing a partial response. The treatment kills off normal antibody-producing B cells too, but patients can be given regular infusions of antibodies to compensate for this, Porter says.

"I was sure the war was on," the patient, who has asked to remain anonymous, wrote in a statement released to reporters. "It was another week later that I got the news that my bone marrow was completely free of detectable disease."

References
1. Porter, D. L. et al. N. Engl. J. Med. doi:10.1056/nejmoa1103849 (2011).
2. Kalos, M. et al. Sci. Transl. Med. 3, 95ra73 (2011).
3. Morgan, R. A. et al. Mol. Ther. 18, 843-851 (2010). | Article | PubMed | ISI | ChemPort |
4. Brentjens, R., Yeh, R., Bernal, Y., Riviere, I. & Sadelain, M. et al. Mol. Ther. 18, 666-668 (2010). | Article | PubMed | ISI | ChemPort |
5. Kochenderfer, J. N. et al. Blood 116, 4099-4102 (2010). | Article | PubMed | ISI | ChemPort |

You can read the entire article here

Gene therapy offers hope for Parkinson's disease

2011-08-10T06:28:00.001-07:00

An experimental gene-therapy treatment for Parkinson's disease has eased the movement problems of a small number of patients and raised no major safety concerns. The study, reported in The Lancet Neurology¹, is the first double-blind clinical trial to show a benefit of gene therapy to patients with the neurodegenerative condition.

Parkinson's disease is characterized by tremors, slowness and cognitive problems, and is caused by the death of neurons in brain circuits that makes dopamine. The effects cascade through interconnected brain regions involved in movement, with some areas becoming overactive.

Many patients are treated with the drug levadopa (L-DOPA), a chemical precursor of dopamine, and regain control of their movements. Over time, however, patients become less sensitive to L-DOPA and burdened by its side effects, which include psychological and physical problems.

Long-term fix

Gene therapy could offer a longer-lasting solution, says Andrew Feigin, a neurologist at the Feinstein Institute for Medical Research in Manhasset, New York, who led the trial along with Michael Kaplitt, at Weill Cornell Medical College in New York and Matthew During, at Ohio State University in Columbus. This involved 45 patients aged between 30 and 75 years old, and was funded by Neurologix of Fort Lee, New Jersey, which holds the patent for the therapy.

Half of the patients received an infusion of a virus engineered to deliver a gene called glutamic acid decarboxylase (GAD) into a brain centre that is overactive in Parkinson's disease — the subthalamic nucleus. GAD encodes a neurotransmitter called GABA, which quiets neurons in this area. Another treatment for Parkinson's, deep brain stimulation (DBS), uses electricity to silence neurons in the same region.

The remaining patients underwent brain surgery, but did not receive the gene therapy.

Six months after these surgeries, Feigin's team measured improvements in both sets of patients using a standardized assessment of Parkinson's disease that looks at factors such as gait, posture, and hand and finger movements. Patients who had received the gene therapy exhibited a 23.1% improvement on this scale, compared with a 12.7% boost for patients who had undergone the placebo surgery. However, patients given the gene therapy did not, as a whole, see any more quality-of-life benefits than the other group.

Feigin's team excluded six patients who may not have received the gene therapy because of problems in its delivery. He says that this is justifiable in a small trial intended to test whether or not a treatment works. "If you included people who didn't get the therapy it could easily wash out the benefit you might see," he says.

In safe hands

One patient who received the gene therapy required treatment for a bowel obstruction 4 months after surgery, but Feigin says this was not related to the therapy.

"I'm very excited to see that it's safe," says Stéphane Palfi, a neurosurgeon at Henri Mondor Hospital in Creteil, France who was not involved in the trial.

However, he notes that DBS typically offers much more benefit to patients with Parkinson's disease. And, he adds, unlike gene therapy, DBS can be tuned up or down depending on a patient's current condition.

Despite this, Palfi remains enthusiastic that gene therapy could provide another tool with which to manage Parkinson's disease. He is involved in an early-stage safety trial for delivering genes involved in making dopamine to the brains of patients with Parkinson's disease. Palfi says that, so far, nine people have received the treatment.

Other scientists are testing gene therapies that prevent neuron from dying in patients with Parkinson's disease.

Marc Panoff, chief financial officer at Neurologix, says that the company will seek permission from the US Food and Drug Administration later this year to conduct a larger clinical trial.

Source: http://www.nature.com/news/2011/110317/full/news.2011.167.html

‘Humanized' mice is latest MIT medical breakthrough

2011-07-13T19:56:00.000-07:00

A team led by Sangeeta Bhatia, a biomedical engineer at the Massachusetts Institute of Technology in Cambridge, made 20-millimetre-long artificial human livers and implanted them into otherwise normal mice. The researchers report today in Proceedings of the National Academy of Sciences that the mice showed metabolism characteristic of the human liver for weeks after implantation.

Although scientists commonly use mice for biomedical research, they are not always helpful for pharmaceutical testing. Because mouse livers react to drugs differently than human livers, they often can't be used to predict whether a potential drug will be toxic to people. That means that a drug that harms the liver could make it all the way to human clinical trials before researchers discover its risks.

"What's exciting to researchers is this idea that if we can create these mice with human livers, we can basically create a slew of human-like patients to do drug-development screens, or to ... develop new therapies," says Alice Chen, an author on the study who works in the lab of Sangeeta Bhatia, the John and Dorothy Wilson Professor of HST and Electrical Engineering and Computer Science.

"The key technique is that we make stable liver implants in the laboratory first," says biomedical engineer Chen The researchers combined human liver cells (hepatocytes) that carry out the liver's metabolic functions, with mouse fibroblast cells and human liver endothelial cells, which provide chemical signals the hepatocytes need to function. They encased the cell packages in a plastic scaffold and implanted them into mice.

When they gave the mice drugs that humans and mice break down differently, the mice produced the same breakdown products (metabolites) and showed the same metabolic interactions between drugs as a human would. The authors hope that the new technology will make drug development safer and less costly, by spotting toxicities before a drug gets to clinical trials.

You can read more of this fascinating story here and here

Gene therapy offers hope for Parkinson's disease

2011-05-19T07:07:00.001-07:00

Long-term fix

The remaining patients underwent brain surgery, but did not receive the gene therapy.

In safe hands

One patient who received the gene therapy required treatment for a bowel obstruction 4 months after surgery, but Feigin says this was not related to the therapy.

"I'm very excited to see that it's safe," says Stéphane Palfi, a neurosurgeon at Henri Mondor Hospital in Creteil, France who was not involved in the trial.

Other scientists are testing gene therapies that prevent neuron from dying in patients with Parkinson's disease.

Marc Panoff, chief financial officer at Neurologix, says that the company will seek permission from the US Food and Drug Administration later this year to conduct a larger clinical trial.

Source: http://www.nature.com/news/2011/110317/full/news.2011.167.html

China, Australia to collaborate on genetic research

2011-05-19T06:59:00.001-07:00

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

High Cholesterol protects against Infections

2009-06-06T07:18:00.000-07:00

A very good read..Many researchers have suggested that the blood lipids play a key role in the immune defence system. There is also a growing understanding that an inflammatory response of the arterial intima to injury is a crucial step in the genesis of atherosclerosis. and that infections may be one type of such injury.22 These two concepts are difficult to harmonize with the low-density-lipoprotein (LDL) receptor hypothesis, according to which high LDL cholesterol is the most important cause of atherosclerosis. However, the many observations that conflict with the LDL receptor hypothesis, may be explained by the idea that high serum cholesterol and/or high LDL is protective against infection and atherosclerosis.

Read the whole article here

Old Genes Can Learn New Tricks, Horned Beetles Show

2009-06-02T07:53:00.000-07:00

A popular view among evolutionary biologists that fundamental genes do not acquire new functions has been challenged by a new study in the Proceedings of the National Academy of Sciences.

Indiana University Bloomington biologist Armin Moczek and research associate Debra Rose report that two ancient genes were "co-opted" to help build a new trait in beetles -- the fancy antlers that give horned beetles their name. The genes, Distal-less and homothorax, touch most aspects of insect larval development, and have therefore been considered off-limits to the evolution of new traits. In the two horned beetle species Moczek and Rose studied, the genetic sequences of Distal-less and homothorax were hardly different, suggesting the two genes have retained their unique identities because of selective pressures not to change. What changed was not the genes themselves, but when and where they are turned on.

"Evolutionary biologists have a good idea of what it takes to change the shape of a wing, the length of a leg, or the anatomy of an eye," Moczek said. "What we have struggled with, though, is how these traits originate in the first place. How do you evolve that first wing, limb or photoreceptor from a flightless, limbless and blind ancestor?"

To investigate these questions, Moczek and Rose examined three development genes that are so old, all insects have them: Distal-less, homothorax and a third, dachshund. The genes were first characterized in fruit flies, and are categorized as "upstream" regulatory genes because they influence a wide variety of genetic processes in insect cells, such as the development of legs, antennae and wings. Moczek said that in horned beetles, each of the three genes is likely to have hundreds to thousands of downstream targets.

A tenuous consensus among evolutionary biologists was that such genes -- upon which so many different and important processes depend -- could not be easily modified, because any modification would affect countless aspects of the insect's development, any one of which could be bad for the individual insect, reducing its fitness relative to its peers.

Moczek and Rose's PNAS paper confirms one aspect of this idea. All three genes were sequenced and found to be highly conserved, or unchanged, not only among the individuals of each beetle species they examined, but also between the two species, Onthophagus taurus (Italy) and Onthophagus binodis (South Africa), whose lineages diverged about 24 million years ago. But that isn't the whole story.

To understand the effects of the three genes on horned beetle development, Moczek and Rose employed a new and promising technique, RNA interference, which disables the action of specific genes without compromising other genetic processes. Humans are only mimicking nature here; RNA interference is also a natural method of gene regulation in eukaryotes.

Moczek and Rose divided beetle larvae of both species into three treatment groups: no injection, buffer injection with nonsense RNA and buffer injection with RNA interference transcripts designed to disrupt one of three crucial developmental genes.

Moczek and Rose learned that two of the three genes, Distal-less and homothorax, are used by both O. taurus and O. binodis in the development of beetle horns. While Distal-less was found to affect both the development of thorax horns (which form just behind the head) and head horns, homothorax was only found to influence thorax horn development. The gene dachshund appears to have no effect whatsoever on horn development in either species.

"The evolution of novel features does not require the evolution of novel genes," Moczek said. "A lot of innovation can grow from within the organism's genetic toolbox."

More importantly, Moczek and Rose learned all developmental genes are candidates for such recruitment, not just the genes whose development functions are considered non-essential or limited in their effects.

Moczek also says the PNAS paper may compel evolutionary biologists to revisit pleiotropy, the foundational concept of one gene influencing many traits.

"It may be that our understanding of pleiotropy is too simplistic," Moczek said. "Now that we know fundamental development genes can acquire new and diverse functions with relative ease, pleiotropy may not be nearly as constraining as we have thought."

U.S. company finds "safer" way to make stem-like cells

2009-06-01T07:08:00.001-07:00

U.S. researchers said on Thursday they had come up with the safest way yet to make stem-like cells using a patient's ordinary skin cells, this time by using pure human proteins. The team at Harvard University and Massachusetts-based Advanced Cell Technology Inc said their technique involves soaking cells in human proteins that turn back the clock biologically, making the cells behave like powerful embryonic stem cells.

Dr. Robert Lanza of Advanced Cell sees almost immediate commercial applications.

"After a few more flight tests -- in order to assure everything is working properly -- it should be ready for commercial use," Lanza said by e-mail.

He said the company would seek Food and Drug Administration permission to test the cells in people by next year -- a process unlikely to be quick, especially with a brand-new technology such as this one.

Stem cells are the body's master cells, giving rise to all the tissues, organs and blood. Embryonic stem cells are considered the most powerful kind, as each one is pluripotent, with the potential to morph into any type of tissue.

Doctors hope to someday use them to transform medicine, for instance, by regenerating the cells destroyed in type 1 diabetes or regrowing eye cells to reverse blindness.

But embryonic cells require the use of an embryo or cloning technology, and several countries, including the United States, limit funding for such experiments.

Several teams of scientists have homed in on four genes that can turn back the clock in ordinary cells, making them look and act like embryonic stem cells. These so-called induced pluripotent stem cells, or iPS cells, could in theory be made using a patient's own skin, allowing grow-your-own transplants with no risk of rejection.

DIFFICULT WORK

Getting these genes into the cells is not easy, however.

The first attempts used retroviruses, which integrate their own genetic material into the cells they infect. Others used loops of genetic material called plasmids or other genetically engineered molecules to reformat the cells.

And another team used the proteins made by the four genes and valproic acid to reprogram cells, but Lanza said these methods all have drawbacks.

His team, working with Kwang-Soo Kim of the Harvard Stem Cell Institute and a team at CHA Stem Cell Institute in South Korea used a peptide, a protein fragment, to drag the human proteins into the cells.

"These have been around for a long time," Lanza said. "The AIDS virus uses the peptide to get into the cells it infects," he said.

Using cells from the foreskins of newborn boys -- a common laboratory technique -- they showed they could transform the cells into iPS cells. They regrew them into a variety of mature new cell types, they reported in the journal Cell Stem Cell.

"This method eliminates the risks associated with genetic and chemical manipulation, and provides for the first time a potentially safe source of iPS cells for translation into the clinic," Lanza said.

"This is the ultimate stem cell solution -- you just add some proteins to a few skin cells and voila! Patient-specific stem cells!"

One question that is not clear is who owns the technology. Lanza said many groups have tried to patent the various steps in the process and it is not yet clear whose patents will prevail.

New Cellular Targets For HIV Drug Development

2009-05-29T07:23:00.000-07:00

Focusing HIV drug development on immune cells called macrophages instead of traditionally targeted T cells could bring us closer to eradicating the disease, according to new research from University of Florida and five other institutions.

In the largest study of its kind, researchers found that in diseased cells — such as cancer cells — that are also infected with HIV, almost all the virus was packed into macrophages, whose job is to "eat" invading disease agents.

What's more, up to half of those macrophages were hybrids, formed when pieces of genetic material from several parent HIV viruses combined to form new strains.

Such "recombination" is responsible for formation of mutants that easily elude immune system surveillance and escape from anti-HIV drugs.

"Macrophages are these little factories producing new hybrid particles of the virus, making the virus probably even more aggressive over time," said study co-author Marco Salemi, Ph.D., an assistant professor in the department of pathology, immunology and laboratory medicine at the UF College of Medicine. "If we want to eradicate HIV we need to find a way to actually target the virus specifically infecting the macrophages."

At least 1.1 million people in the United States and 33 million in the world are living with HIV/AIDS, according to the Kaiser Family Foundation.

The researchers set out to see if HIV populations that infect abnormal tissues are different from those that infect normal ones, and whether particular strains are associated with certain types of illness.

They tackled the question using frozen post-autopsy tissue samples, pathology results and advanced computational techniques. They analyzed 780 HIV sequences from 53 normal and abnormal tissues from seven patients who had died between 1995 and 2003 from various AIDS-related conditions, including HIV-associated dementia, non-Hodgkin's lymphoma and generalized infections throughout the body. Four patients had been treated with highly active antiretroviral therapy, called HAART, at or near the time of death.

The researchers compared brain and lymphoma tissues, which had heavy concentrations of macrophages, with lymphoid tissues — such as from the spleen and lymph nodes— that had a mix of HIV-infected macrophages and T cells.

The analyses revealed great diversity in the HIV strains present, with different tissues having hybrid viruses made up of slightly different sets of genes. A high frequency of such recombinant viruses was also found in tissues generally associated with disease processes, such as the meninges, spleen and lymph nodes.

The researchers concluded that HIV-infected macrophages might be implicated in tumor-producing mechanisms.

The higher frequency of recombinant virus in diseased tissues likely is because macrophages multiply as a result of an inflammatory response, the researchers said.

"The study points to macrophages as a site of recombination in active disease," said neurobiologist Kenneth C. Williams, Ph.D., a Boston College associate professor and AIDS expert who was not involved in the study. "So people can say this is one spot where these viruses come from."

T cells — the so-called conductors of the immune system orchestra, whose decline is the hallmark of HIV disease — are an obvious target for HIV drug development because they die soon after infection, and are readily sampled from the blood and cultured. But although current drugs are effective at blocking infection of new cells and lowering viral loads to barely detectable levels, they never reduce the viral level in an infected person to zero.

"Where is it coming from?" said Michael S. McGrath, the University of California, San Francisco, professor who led the research team. "We believe it's coming from these macrophages."

Macrophages, like T cells, can be infected multiple times by HIV. But unlike T cells, when they get infected, they don't die within days, but live for several months, all the while being re-infected with multiple viruses of different genetic makeup. That situation is ripe for the emergence of hybrids.

"Most people who look at viral sequences assume that evolution of the virus is linear. In the real world that doesn't happen — large parts of the virus are swapped in and out. This group has shown that in this model," Williams said. "It sort of overturns the old way of trying to match virus sequence with pathology."

McGrath's group is now developing macrophage-targeting drugs that, through a grant from the National Institute of Mental Health, should be in human clinical trials in a few years.

"This is one of the last frontiers — killing off what we believe is a so far untouched reservoir," he said.

The work was published recently in the journal PLoS One.

Gene-laden Bubbles Grow New Blood Vessels

2009-05-24T00:15:00.000-07:00

Progress in human gene therapy -- the insertion of therapeutic DNA into tissues and cells in the human body -- has been slower than expected since the first clinical trials in 1990. One of the biggest challenges for this technology is finding ways to safely and effectively deliver genes only to the specific parts of the body that they are meant to treat.

Cardiologist Jonathan Lindner of Oregon Health and Science University will discuss his latest experiments in gene therapy, which use microscopic bubbles chemically modified to stick to the cells that line blood vessels.

This technique, ultrasound-mediated gene delivery (UMGD), exploits the properties of contrast agents, microparticles that are normally injected into the body to improve the quality of ultrasound images. In UMGD, the tiny particles are microbubbles composed of pockets of gas encapsulated by thin membranes that are coated with DNA before injection. A targeted pulse of ultrasound energy "rings" the bubbles like a bell, popping them in a specific location and releasing the DNA into the surrounding tissue.

To improve the specificity of this targeting, Lindner grafts long arm-like molecules to the outside of the bubbles. These arms, which do not interfere with the DNA attached to surface, are designed to recognize and bind to molecules on the outside of specific cells in the body, allowing the bubbles to attach to a tissue before being popped. In theory, this should improve both the specificity and efficiency of the gene therapy.

Lindner created an arm designed to attach to endothelial cells lining blood vessels. He will present data evaluating the behavior of these "targeted" bubbles in living tissue. The ability to stick these gene-laden microbubbles to the lining of blood vessels increased the amount of gene transfection. This strategy may be particularly important for delivering therapeutic DNA to the walls of blood vessels. For example, Dr. Lindner and collaborators have successfully stimulated the growth of new blood vessels using UMGD with microbubbles carrying a gene for vascular endothelial growth factor. This therapeutic use could be important for treating ischemia in patients who have had a heart attack, peripheral artery disease, or stroke.

The team is also investigating using the bubbles to transport small doses of drugs. "If you're trying to deliver a nasty drug to part of the body, this may be a way to improve safety," says Lindner.

The talk "Targeted microbubble technology and ultrasound-mediated gene delivery" by Jonathan Lindner will be presented at the 157th Acoustical Society of America Meeting to be held May 18-22 in Portland, Ore.

Fish Oil Protects Against Diseases Like Parkinson's

2009-05-16T03:15:00.000-07:00

Dr. Nicolas Bazan, Director of the Neuroscience Center of Excellence, Boyd Professor, and Ernest C. and Yvette C. Villere Chair of Retinal Degenerative Diseases Research at LSU Health Sciences Center New Orleans, will present new research findings showing that an omega three fatty acid in the diet protects brain cells by preventing the misfolding of a protein resulting from a gene mutation in neurodegenerative diseases like Parkinson's and Huntington's.

He will present these findings for the first time on April 19, 2009 at the Ernest N. Morial Convention Center, Nouvelle C Room, at the American Society for Nutrition, Experimental Biology 2009 Annual Meeting.

With funding from the National Eye Institute of the National Institutes of Health, Dr. Bazan and his colleagues developed a cell model with a mutation of the Ataxin-1 gene. The defective Ataxin-1 gene induces the misfolding of the protein produced by the gene. These misshapened proteins cannot be properly processed by the cell machinery, resulting in tangled clumps of toxic protein that eventually kill the cell. Spinocerebellar Ataxia, a disabling disorder that affects speech, eye movement, and hand coordination at early ages of life, is one disorder resulting from the Ataxin-1 misfolding defect. The research team led by Dr. Bazan found that the omega three fatty acid, docosahexaenoic acid (DHA), protects cells from this defect.

Dr. Bazan's laboratory discovered earlier that neuroprotectin D1 (NPD1), a naturally-occurring molecule in the human brain that is derived from DHA also promotes brain cell survival. In this system NPD1 is capable of rescue the dying cells with the pathological type of Ataxin-1, keeping their integrity intact.

"These experiments provide proof of principle that neuroprotectin D1 can be applied therapeutically to combat various neurodegenerative diseases," says Dr. Bazan. "Furthermore, this study provides the basis of new therapeutic approaches to manipulate retinal pigment epithelial cells to be used as a source of NPD1 to treat patients with disorders characterized by this mutation like Parkinson's, Retinitis Pigmentosa and some forms of Alzheimer's Disease."

Earliest Evidence Of Domesticated Maize Discovered: Dates Back 8,700 Years

2009-05-10T19:33:00.000-07:00

This is so fascinating. According to Ranere, recent studies have confirmed that maize derived from teosinte, a large wild grass that has five species growing in Mexico, Guatemala and Nicaragua. The teosinte species that is closest to maize is Balsas teosinte, which is native to Mexico's Central Balsas River Valley.

"We went to the area where the closest relative to maize grows, looked for the earliest maize and found it," said Ranere. "That wasn't surprising since molecular biologists had determined that Balsas teosinte was the ancestral species to maize. So it made sense that this was where we would find the earliest domestication of maize."

The study began with Piperno, a Temple University anthropology alumna, finding evidence in the form of pollen and charcoal in lake sediments that forests were being cut down and burned in the Central Balsas River Valley to create agricultural plots by 7000 years ago. She also found maize and squash phytoliths -- rigid microscopic bodies found in many plants -- in lakeside sediments.

Ranere, an archaeologist, joined in the study to find rock shelters or caves where people lived in that region thousands of years ago. His team carried out excavations in four of the 15 caves and rock shelters visited in the region, but only one of them yielded evidence for the early domestication of maize and squash.

Ranere excavated the site and recovered numerous grinding tools. Radiocarbon dating showed that the tools dated back at least 8700 years. Although grinding tools were found beneath the 8700 year level, the researchers were not able to obtain a radiocarbon date for the earliest deposits. Previously, the earliest evidence for the cultivation of maize came from Ranere and Piperno's earlier research in Panama where maize starch and phytoliths dated back 7600 years.

Ranere said that maize starch, which is different from teosinte starch, was found in crevices of many of the tools that were unearthed.

"We found maize starch in almost every tool that we analyzed, all the way down to the bottom of our site excavations," Ranere said. "We also found phytoliths that comes from maize or corn cobs, and since teosinte doesn't have cobs, we knew we had something that had changed from its wild form."

Ranere said that their findings also supported the premise that maize was domesticated in a lowland seasonal forest context, as opposed to being domesticated in the arid highlands as many researchers had once believed.

"For a long time, I though it strange that researchers argued about the location and age of maize domestication yet never looked in the Central Balsas River Valley, the homeland for the wild ancestor," said Ranere. "Dolores was the first one to do it.'

In addition to Ranere and Piperno, other researchers in the study included Irene Holst of the Smithsonian Tropical Research Institute, Ruth Dickau of Temple, and Jose Iriarte of the University of Exeter. The study was funded by the National Science Foundation, National Geographic Society, Wenner-Gren Foundation, Smithsonian National Museum of Natural History, Smithsonian Tropical Research Institute and the Temple University College of Liberal Arts.

Glucose-To-Glycerol Conversion In Long-lived Yeast Provides Anti-aging Effects

2009-05-06T14:38:00.000-07:00

Cell biologists have found a more filling substitute for caloric restriction in extending the life span of simple organisms. In a study published May 8 in the open-access journal PLoS Genetics, researchers from the University of Southern California Andrus Gerontology Center show that yeast cells maintained on a glycerol diet live twice as long as normal -- as long as yeast cells on a severe caloric-restriction diet. They are also more resistant to cell damage.

Many studies have shown that caloric restriction can extend the life span of a variety of laboratory animals. Caloric restriction is also known to cause major improvements in a number of markers for cardiovascular diseases in humans. This study is the first to propose that "dietary substitution" can replace "dietary restriction" in a living species.

"If you add glycerol, or restrict caloric intake, you obtain the same effect," said senior author Valter Longo. "It's as good as calorie restriction, yet cells can take it up and utilize it to generate energy or for the synthesis of cellular components."

Longo and colleagues Min Wei and Paola Fabrizio introduced a glycerol diet after discovering that genetically engineered long-lived yeast cells that survive up to 5-fold longer than normal have increased levels of the genes that produce glycerol. In fact, they convert virtually all the glucose and ethanol into glycerol. Notably, these cells have a reduced activity in the TOR1/SCH9 pathway, which is also believed to extend life span in organisms ranging from worms to mice.

When the researchers blocked the genes that produce glycerol, the cells lost most of their life span advantage. However, Longo and colleagues believe that the "glucose to glycerol" switch represents only a component of the protective systems required for the extended survival. The current study indicates that glycerol biosynthesis is an important process in the metabolic switch that allows this simple organism to activate its protective systems and live longer.

"This is a fundamental observation in a very simple system," Longo said, "that at least introduces the possibility that you don't have to be calorie-restricted to achieve some of the remarkable protective effects of the hypocaloric diet observed in many organisms, including humans. It may be sufficient to substitute the carbon source and possibly other macronutrients with nutrients that do not promote the "pro-aging" changes induced by sugars."

Funding for the study came from the American Federation for Aging Research and the National Institute on Aging (NIH).

Groundbreaking Study Reveals Intermediary Steps Of Genetic Encoding For The First Time

2009-05-05T10:13:00.000-07:00

The scientists report that they were able to crystallize a very large complex of a macromolecular "machine" in the human cell and determine its structure or what it actually looks like, thereby zeroing in on the process of genetic encoding. Importantly, 15 to 20 percent of all human genetic disorders, including muscular dystrophy, are caused by defects in this genetic encoding process known as RNA splicing.

Using x-ray crystallography, the scientists for the first time were able to create a three-dimensional structure of an integral complex of the human spliceosome, which consists of specialized RNA and protein subunits. The spliceosome's job is to modify the message relayed from our genetic material—DNA—by clipping, or splicing, genetic bits in such a manner that they are acceptable for translation into protein. Importantly, the spliceosome also rearranges the genetic bits of the message in such a way that it can generate multiple and varied proteins which can and do have dramatic effects on human development, said lead author and Brandeis biochemist Daniel Pomeranz Krummel.

"The process of RNA splicing is vital to human cell development and survival," said Pomeranz Krummel. "In this process, the regions of our DNA encoding for protein are removed from non-encoding regions and brought together—quite often in alternative arrangements. Defects in this process can have disasterous repercussions in the form of genetic disorders," said Pomeranz Krummel, adding that neuronal development can be particularly affected when things go awry. Indeed, defects in this process have recently been implicated in various human neurological disorders, including epilepsy.

Specifically, this macromolecular machine clips, or splices, gene sequences transcribed as part of a precursor to the mRNA, removing them before the final mRNA product is translated into protein. The spliceosome must clip these sequences, known as introns, at the right place in the precursor mRNA.

"In human cells one gene can be made into a variety of proteins, so if the process just goes slightly wrong, the genetic alteration can lead to incredible disaster; yet on the other hand, this incredible complexity has led to our amazing evolutionary progress," said Pomeranz Krummel. "The human genome is not terribly different from the earthworm's with regards to its size, but the process of RNA splicing that occurs in our cells is different. The fundamental difference between us and the earthworm is that our cells have evolved to utilize this process of RNA splicing to generate a whole other dimension to the transmission of genetic information."

Pomeranz Krummel's lab will next focus on understanding how this complex interacts with other macromolecular machines in the human cell. The study was funded by the Medical Research Council (U.K.) and the Human Frontier Science Program.

Did you know?? Omega-3 Kills Cancer Cells

2009-04-21T23:53:00.000-07:00

Docosahexanoic acid (DHA), an omega-3 fatty acid found in fish oils, has been shown to reduce the size of tumours and enhance the positive effects of the chemotherapy drug cisplatin, while limiting its harmful side effects. The rat experiments provide some support for the plethora of health benefits often ascribed to omega-3 acids.

DHA is an omega-3 fatty acid that is commonly found in cold-water fish oil, and some vegetable oils. It is a major component of brain gray matter and of the retina in most mammalian species and is considered essential for normal neurological and cellular developments. According to the authors, "While DHA has been tentatively linked with protection against cardiovascular, neurological and neoplastic diseases, there exists a paucity of research information, in particular regarding its interactions with existing chemotherapy drugs". The researchers found that, at the molecular level, DHA acts by reducing leukocytosis (white blood cell accumulation), systemic inflammation, and oxidative stress – all processes that have been linked with tumour growth.

El-Mowafy and his colleagues have called for greater deployment of omega-3 in the fight against cancer. They write, "Our results suggest a new, fruitful drug regimen in the management of solid tumors based on combining cisplatin, and possibly other chemotherapeutics, with DHA".

Human Genes Required For Hepatitis C Viral Replication Identified

2009-04-13T10:44:00.000-07:00

Massachusetts General Hospital (MGH) researchers are investigating a new way to block reproduction of the hepatitis C virus (HCV) – targeting not the virus itself but the human genes the virus exploits in its life cycle. In the March 19 Cell Host & Microbe, they report finding nearly 100 genes that support the replication of HCV and show that blocking several of them can suppress viral replication in cultured cells.

"We identified a large number of genes that have not been previously known to be involved in hepatitis C replication," says Raymond Chung, MD, director of Hepatology in the MGH Gastrointestinal Unit, the study's senior author.

Lead author Andrew Tai, MD, PhD, also of the MGH Gastrointestinal Unit, adds, "We may be a few years away from developing therapies based on these findings, but this study is a proof of principle that targeting host factors is a viable therapeutic strategy."

Usually spread by blood-to-blood contact, HCV infection becomes chronic in 70 to 80 percent of patients, and long-term infection can lead to liver failure or liver cancer. Today HCV-related liver disease is the most common diagnosis underlying the need for liver transplantation. HCV infection is usually treated with a six- to eleven-month regimen combining peginterferon and the antiviral drug ribavirin, but treatment is not successful in many patients and has serious side effects some cannot tolerate. Other therapies targeting viral enzymes are being developed, but there is concern that HCV's ability to mutate rapidly would lead to the emergence of resistant strains, so strategies directed against factors in the infected host rather than the virus may offer a complementary approach.

These strategies are being explored in a number of diseases – including influenza, West Nile virus and HIV – and previous studies have scanned a limited number of human genes for host cofactors of HCV infection. For the current study the researchers examined whether blocking each of the approximately 21,000 predicted messenger RNA transcripts in the human genome with small interfering RNAs (siRNAs) had any effect on HCV replication. Chung notes that this approach does not rely on any prior assumptions about gene function and can thereby identify genes not previously suspected of involvement.

The siRNA scan found 96 genes that appear to have a role in viral replication, and the research team studied several of them in greater detail. One gene codes for an enzyme called PI4KA, which is believed to be involved in the formation of membrane structures within the cell that may be the site of HCV replication. Another group of genes contribute to formation of the COPI coat that covers several types of cellular vesicles and is known to have a role in the replication of poliovirus. The researchers also focused on the gene for hepcidin, a liver protein that regulates iron absorption, since iron levels in the blood and liver rise in chronic HCV infection. They found that blocking each of these genes also blocked HCV replication, as did drugs that inhibit PI4KA and COPI, although the tested agents might not be suitable for therapeutic use.

"Now we need to work to uncover the molecular mechanisms by which these genes support HCV replication to get a better idea of which would be advantageous therapeutic targets," explains Chung, an associate professor of Medicine at Harvard Medical School.

Additional co-authors of the Cell Host & Microbe paper are Yair Benita, PhD, Sun-Suk Kim, MD, and Ramnik Xavier, MB,ChB, MGH Gastrointestinal Unit; and Naoya Sakamoto, MD, PhD,Tokyo Medical and Dental University. The study was supported by grants from the National Institutes of Health, the Massachusetts Biomedical Research Corporation, the American Gastrointestinal Association and the American Liver Foundation.

Synthetic Biology and Gene Synthesis

Types of Stem Cells

1. Adult Stem Cells or Tissue-specific Stem Cells

2. Fetal Stem Cells

3. Cord Blood Stem Cells

4. Embryonic Stem Cells

5. Induced Pluripotent Stem Cells (iPS cells)

What are stem cells and why are they important?

Stem Cells - The Basics

Stem Cells and Everything you need to know

Hillary Clinton warns of gene assembly's ability to create bioweapons

Genes Predict Mesothelioma Treatment Response

Stem cell cure for hearing loss in aged

Today's lifestyles, tomorrow's cancers: trends in lifestyle risk factors for cancer in low- and middle-income countries

Existing Technique Can Detect Fetal Genetic Abnormalities in Maternal Blood

Cell therapy fights leukaemia

References

Gene therapy offers hope for Parkinson's disease

Long-term fix

In safe hands

‘Humanized' mice is latest MIT medical breakthrough

Gene therapy offers hope for Parkinson's disease

Long-term fix

In safe hands

China, Australia to collaborate on genetic research

High Cholesterol protects against Infections

Old Genes Can Learn New Tricks, Horned Beetles Show

U.S. company finds "safer" way to make stem-like cells

New Cellular Targets For HIV Drug Development

Gene-laden Bubbles Grow New Blood Vessels

Fish Oil Protects Against Diseases Like Parkinson's

Earliest Evidence Of Domesticated Maize Discovered: Dates Back 8,700 Years

Glucose-To-Glycerol Conversion In Long-lived Yeast Provides Anti-aging Effects

Groundbreaking Study Reveals Intermediary Steps Of Genetic Encoding For The First Time

Did you know?? Omega-3 Kills Cancer Cells

Human Genes Required For Hepatitis C Viral Replication Identified