Mice Cloned from Skin Cells

Healthy and viable mice that survive until adulthood have, for the first time, been cloned from adult stem cells. Scientists from Rockefeller University, including Howard Hughes Medical Institute investigator Elaine Fuchs, used cells called keratinocyte stem cells, which represent a new model system for cloning. Keratinocytes come from the skin, making them a particularly attractive stem cell source because of their ready accessibility. One day, they could be used to tailor therapies, as well as to better understand and treat diseases.

Original Article

Links between cancer and aging

Wielding a palette of chromosome paints, scientists at the Salk Institute for Biological Studies have taken a step closer to understanding the relationship between aging and cancer by visualizing chromosomes of cells from patients with a heritable premature aging disease known as Werner Syndrome.
 
In a study to be published in this week�s online edition of the Proceedings of the National Academy of Sciences researchers led by Jan Karlseder, Ph.D., assistant professor in Salk�s Regulatory Biology Laboratory, showed that rebuilding structures called telomeres, which are found at the tips of each chromosome, significantly blocks the type of genetic damage seen in cells of patients with Werner Syndrome.

 

Patients with Werner Syndrome manifest signs of aging, such as skin wrinkling, baldness, or hair graying, in their teens. Most die in their 40�s or 50�s due to a predisposition to diseases like cancer. �Cancer is almost always related to chromosomal instability,� explains Karlseder. �If telomeres are lost on individual chromosomes, then chromosomes are not protected and can fuse with other nonprotected chromosomes. Then when cells divide, chromosomes randomly break, leading to genome instability.�

 

Original Article

Carnegie Mellon Mechanical Engineering Researcher Proposes Development of Artificial Cells To Fight Disease

PITTSBURGH�Carnegie Mellon University's Philip LeDuc predicts the use of artificially created cells could be a potential new therapeutic approach for treating diseases in an ever-changing world.     Philip LeDuc

 

LeDuc, an assistant professor of mechanical and biomedical engineering, penned an article for the January edition of Nature Nanotechnology Journal about the efficacy of using man-made cells to treat diseases without injecting drugs. This idea was developed by a team of researchers from disciplines including biology, chemistry and engineering during an exciting conference organized by the National Academies and the Keck Foundation for developing new disease-fighting approaches for the future.

 

"Our proposal is to use naturally available molecules to create pseudo-cell factories where we create a super artificial cell capable of targeting and treating whatever is ailing the body. The human cell is like a bustling metropolis, and we aim to tap the energy and diversity of the processes in a human cell to help the body essentially heal itself," LeDuc said.  

 

Because the cell is an amazingly efficient system already, LeDuc and his team of researchers plan to use its microscopic package of tightly organized parts to improve medical treatment in diseases that exist in the body.    

 

According to LeDuc's journal article, the living cell operates much like a tiny industrial complex. His article proposes using the processes in a cell, such as the membrane, to create an enclosed functioning environment for a nanofactory. Then, by using other biologically inspired processes like molecular-binding and transport, the pseudo-cell can target, modify and deliver chemicals that the body needs to function properly.

 

In contrast to traditional drug-discovery ideas, where the product is delivered many times into the body, this journal article suggests using molecules that are already in the body and modifying these nanoscale systems to produce the biochemicals deficient in the body to help fight disease.    

 

"Understanding both the nature of a cell as an independent unit and its role in the life processes of larger organisms is crucial in our quest to duplicate the molecular units which form the building blocks of the cell and its parts," LeDuc said. "We see this development of artificial cells as a building block for a variety of new and exciting therapeutic approaches."

 

Original Article

Explaining How Mitochondrial Aging Leads to Diabetes

As we age, the mitochondrial �motors� that power our cells start to lose their horsepower. This drop-off in mitochondrial activity predisposes us to accumulate intracellular fat in muscle and liver cells, which can lead to insulin resistance and type 2 diabetes. A new study directed by Howard Hughes Medical Institute investigator Gerald I. Shulman has shown how changes in an enzyme known to be vital to the body's energy levels may lead to a decreasing ability to stave off diabetes as we get older.

 

�Type 2 diabetes is a major problem for us as we age,� says Shulman, pointing to the 40 percent of people over age 65 who suffer from type 2 diabetes or impaired glucose tolerance. Hoping to unravel how aging affects the components of the cell's energy production system, Shulman and colleagues at Yale University studied the effects of aging on the activity of AMP-activated protein kinase (AMPK).

 

Original Article

Man-made Proteins Could Be More Useful than Real Ones

Researchers have constructed a protein out of amino acids not found in natural proteins, discovering that they can form a complex, stable structure that closely resembles a natural protein. Their findings could help scientists design drugs that look and act like real proteins but won't be degraded by enzymes or targeted by the immune system, as natural proteins are.

 

The researchers, led by Howard Hughes Medical Institute (HHMI) professor Alanna Schepartz, report their findings in the February 14, 2007, issue of the Journal of the American Chemical Society, published in advance online on January 19, 2007. Schepartz and her coauthors, Douglas Daniels, James Petersson, and Jade Qiu, are all at Yale University. A story in the February 5, 2007, issue of Chemical & Engineering News spotlighted the research.

 

Original Article

Cheap, safe drug kills most cancers

IT SOUNDS almost too good to be true: a cheap and simple drug that kills almost all cancers by switching off their "immortality". The drug, dichloroacetate (DCA), has already been used for years to treat rare metabolic disorders and so is known to be relatively safe. It also has no patent, meaning it could be manufactured for a fraction of the cost of newly developed drugs.

Evangelos Michelakis of the University of Alberta in Edmonton, Canada, and his colleagues tested DCA on human cells cultured outside the body and found that it killed lung, breast and brain cancer cells, but not healthy cells. Tumours in rats deliberately infected with human cancer also shrank drastically when they were fed DCA-laced water for several weeks.

DCA attacks a unique feature of cancer cells: the fact that they make their energy throughout the main body of the cell, rather than in distinct organelles called mitochondria. This process, called glycolysis, is inefficient and uses up vast amounts of sugar. Until now it had been assumed that cancer cells used glycolysis because their mitochondria were irreparably damaged. However, Michelakis's experiments prove this is not the case, because DCA reawakened the mitochondria in cancer cells. The cells then withered and died (Cancer Cell, DOI: 10.1016/j.ccr.2006.10.020).

Michelakis suggests that the switch to glycolysis as an energy source occurs when cells in the middle of an abnormal but benign lump don't get enough oxygen for their mitochondria to work properly (see Diagram). In order to survive, they switch off their mitochondria and start producing energy through glycolysis.

Crucially, though, mitochondria do another job in cells: they activate apoptosis, the process by which abnormal cells self-destruct. When cells switch mitochondria off, they become "immortal", outliving other cells in the tumour and so becoming dominant. Once reawakened by DCA, mitochondria reactivate apoptosis and order the abnormal cells to die.

"The results are intriguing because they point to a critical role that mitochondria play: they impart a unique trait to cancer cells that can be exploited for cancer therapy," says Dario Altieri, director of the University of Massachusetts Cancer Center in Worcester.

The phenomenon might also explain how secondary cancers form. Glycolysis generates lactic acid, which can break down the collagen matrix holding cells together. This means abnormal cells can be released and float to other parts of the body, where they seed new tumours.

DCA can cause pain, numbness and gait disturbances in some patients, but this may be a price worth paying if it turns out to be effective against all cancers. The next step is to run clinical trials of DCA in people with cancer. These may have to be funded by charities, universities and governments: pharmaceutical companies are unlikely to pay because they can't make money on unpatented medicines. The pay-off is that if DCA does work, it will be easy to manufacture and dirt cheap.

Paul Clarke, a cancer cell biologist at the University of Dundee in the UK, says the findings challenge the current assumption that mutations, not metabolism, spark off cancers. "The question is: which comes first?" he says.
From issue 2587 of New Scientist magazine, 20 January 2007, page 13

Original Article