SCIENTISTS REVEAL HOW LUNG CANCER SPREADS

Scientists have revealed the mystery behind spreading of lung cancer.

The researchers at the Cancer Research UK Manchester Institute discovered that the ties which lash cells together - controlled by a protein called TIAM1 - were chopped up when cell maintenance work goes wrong.

Healthy cells routinely scrap old cell parts so they could be broken down and used again. But this process spiraled out of control in lung cancer cells, which scraped too many TIAM1 ties.

Targeting this recycling process could stop lung cancer from spreading by keeping the cells stuck firmly together.

Lead researcher, Dr Angeliki Malliri, at the Cancer Research UK Manchester Institute at the University of Manchester, said that the research showed for the first time how lung cancer cells severed ties with their neighbours and start to spread around the body, by hijacking the cells' recycling process and sending it into overdrive. Targeting this flaw could help stop lung cancer from spreading.

SCIENTISTS CREATE NEW PROTEIN BASED MATERIAL WITH SOME NERVE

Scientists at the University of California, Berkeley, have taken proteins from nerve cells and used them to create a "smart" material that is extremely sensitive to its environment. This marriage of materials science and biology could give birth to a flexible, sensitive coating that is easy and cheap to manufacture in large quantities.

The work, to be published Oct. 14, in the journal Nature Communications, could lead to new types of biological sensors, flow valves and controlled drug release systems, the researchers said. Biomedical applications include microfluidic devices that can handle and process very small volumes of liquid, such as samples of saliva or blood, for diagnostics.

"This work represents a unique convergence of the fields of biomimetic materials, biomolecular engineering and synthetic biology," said principal investigator Dr. Sanjay Kumar, UC Berkeley associate professor of bioengineering. "We created a new class of smart, protein-based materials whose structural principles are inspired by networks found in living cells."

Kumar's research team set out to create a biological version of a synthetic coating used in everyday liquid products, such as paint and liquid cosmetics, to keep small particles from clumping together. The synthetic coatings are often called polymer brushes because of their bristle-like appearance when attached to the particle surface.

To create the biological equivalent of a polymer brush, the researchers turned to neurofilaments, pipe cleaner-shaped proteins found in nerve cells. By acting as tiny, cylindrical polymer brushes, neurofilaments collectively assemble into a structural network that helps keep one end of the nerve cell propped open so that it can conduct electrical signals.

"We co-opted this protein and turned it into a polymer brush by cloning a portion of a gene that encodes one of the neurofilament bristles, re-engineering it such that we could attach the resulting protein to surfaces in a precise and oriented way, and then expressing the gene in bacteria to produce the protein in large, pure quantities," said Kumar. "We showed that our 'protein brush' had all the key properties of synthetic brushes, plus a number of advantages."

Kumar noted that neurofilaments are good candidates for protein brushes because they are intrinsically disordered proteins, so named because they don't have a fixed 3-D shape. The size and chemical sequence of these hair-like proteins are far easier to control when compared with their synthetic counterparts.

"In biology, precision is critical," said Kumar. "Proteins are generally synthesized with the exact same sequence every time; the length and biochemical order of the protein sequence affects all of its properties, including structure and the ability to bind to other molecules and catalyze biochemical reactions. This kind of sequence precision is difficult if not impossible to achieve in the laboratory using the tools of chemical synthesis. By harnessing the precision of biology and letting the bacterial cell do all the work for us, we were able to control the exact length and sequence of the bristles of our protein brush."

The researchers showed that the protein brushes could be grafted onto surfaces, and that they dramatically expand and collapse in reaction to changes in acidity and salinity. Materials that are environmentally sensitive in this way are often referred to as "smart" materials because of their ability to adaptively respond to specific stimuli.

SCIENTISTS GROW LEG MUSCLE FROM CELLS IN A DISH

A team of researchers from Italy, Israel and the United Kingdom has succeeded in generating mature, functional skeletal muscles in mice using a new approach for tissue engineering. The scientists grew a leg muscle starting from engineered cells cultured in a dish to produce a graft. The subsequent graft was implanted close to a normal, contracting skeletal muscle where the new muscle was nurtured and grown. In time, the method could allow for patient-specific treatments for a large number of muscle disorders.

The results are published in EMBO Molecular Medicine.

The scientists used muscle precursor cells -- mesoangioblasts -- grown in the presence of a hydrogel (support matrix) in a tissue culture dish. The cells were also genetically modified to produce a growth factor that stimulates blood vessel and nerve growth from the host. Cells engineered in this way express a protein growth factor that attracts other essential cells that give rise to the blood vessels and nerves of the host, contributing to the survival and maturation of newly formed muscle fibres. After the graft was implanted onto the surface of the skeletal muscle underneath the skin of the mouse, mature muscle fibres formed a complete and functional muscle within several weeks. Replacing a damaged muscle with the graft also resulted in a functional artificial muscle very similar to a normal Tibialis anterior.

Tissue engineering of skeletal muscle is a significant challenge but has considerable potential for the treatment of the various types of irreversible damage to muscle that occur in diseases like Duchenne muscular dystrophy. So far, attempts to re-create a functional muscle either outside or directly inside the body have been unsuccessful. In vitro-generated artificial muscles normally do not survive the transfer in vivo because the host does not create the necessary nerves and blood vessels that would support the muscle's considerable requirements for oxygen.

"The morphology and the structural organisation of the artificial organ are extremely similar to if not indistinguishable from a natural skeletal muscle," says Cesare Gargioli of the University of Rome, one of the lead authors of the study.

In future, irreversibly damaged muscles could be restored by implanting the patient's own cells within the hydrogel matrix on top of a residual muscle, adjacent to the damaged area. "While we are encouraged by the success of our work in growing a complete intact and functional mouse leg muscle we emphasize that a mouse muscle is very small and scaling up the process for patients may require significant additional work," comments EMBO Member Giulio Cossu, one of the authors of the study. The next step in the work will be to use larger animal models to test the efficacy of this approach before starting clinical studies.

DATA SCIENTISTS FIND CONNECTIONS BETWEEN BIRTH MONTH AND HEALTH

Columbia University scientists have developed a computational method to investigate the relationship between birth month and disease risk. The researchers used this algorithm to examine New York City medical databases and found 55 diseases that correlated with the season of birth. Overall, the study indicated people born in May had the lowest disease risk, and those born in October the highest. The study was published in the Journal of American Medical Informatics Association

"This data could help scientists uncover new disease risk factors," said study senior author Nicholas Tatonetti, PhD, an assistant professor of biomedical informatics at Columbia University Medical Center (CUMC) and Columbia's Data Science Institute. The researchers plan to replicate their study with data from several other locations in the U.S. and abroad to see how results vary with the change of seasons and environmental factors in those places. By identifying what's causing disease disparities by birth month, the researchers hope to figure out how they might close the gap.

Earlier research on individual diseases such as ADHD and asthma suggested a connection between birth season and incidence, but no large-scale studies had been undertaken. This motivated Columbia's scientists to compare 1,688 diseases against the birth dates and medical histories of 1.7 million patients treated at NewYork-Presbyterian Hospital/CUMC between 1985 and 2013.

The study ruled out more than 1,600 associations and confirmed 39 links previously reported in the medical literature. The researchers also uncovered 16 new associations, including nine types of heart disease, the leading cause of death in the United States. The researchers performed statistical tests to check that the 55 diseases for which they found associations did not arise by chance.

"It's important not to get overly nervous about these results because even though we found significant associations the overall disease risk is not that great," notes Dr. Tatonetti. "The risk related to birth month is relatively minor when compared to more influential variables like diet and exercise."

The new data are consistent with previous research on individual diseases. For example, the study authors found that asthma risk is greatest for July and October babies. An earlier Danish study on the disease found that the peak risk was in the months (May and August) when Denmark's sunlight levels are similar to New York's in the July and October period.

For ADHD, the Columbia data suggest that around one in 675 occurrences could relate to being born in New York in November. This result matches a Swedish study showing peak rates of ADHD in November babies.

The researchers also found a relationship between birth month and nine types of heart disease, with people born in March facing the highest risk for atrial fibrillation, congestive heart failure, and mitral valve disorder. One in 40 atrial fibrillation cases may relate to seasonal effects for a March birth. A previous study using Austrian and Danish patient records found that those born in months with higher heart disease rates--March through June--had shorter life spans.

"Faster computers and electronic health records are accelerating the pace of discovery," said the study's lead author, Mary Regina Boland, a graduate student at Columbia. "We are working to help doctors solve important clinical problems using this new wealth of data."

ON OFF SWITCH FOR AGING CELLS DISCOVERED BY SCIENTISTS

Scientists at the Salk Institute have discovered an on-and-off “switch” in cells that may hold the key to healthy aging. This switch points to a way to encourage healthy cells to keep dividing and generating, for example, new lung or liver tissue, even in old age.

In our bodies, newly divided cells constantly replenish lungs, skin, liver and other organs. However, most human cells cannot divide indefinitely–with each division, a cellular timekeeper at the ends of chromosomes shortens. When this timekeeper, called a telomere, becomes too short, cells can no longer divide, causing organs and tissues to degenerate, as often happens in old age. But there is a way around this countdown: some cells produce an enzyme called telomerase, which rebuilds telomeres and allows cells to divide indefinitely.

In a new study published September 19 in the journalGenes and Development, scientists at the Salk Institute have discovered that telomerase, even when present, can be turned off.

“Previous studies had suggested that once assembled, telomerase is available whenever it is needed,” says senior author Vicki Lundblad, professor and holder of Salk’s Ralph S. and Becky O'Connor Chair. “We were surprised to discover instead that telomerase has what is in essence an ‘off’ switch, whereby it disassembles.”

Understanding how this “off” switch can be manipulated–thereby slowing down the telomere shortening process–could lead to treatments for diseases of aging (for example, regenerating vital organs later in life).

Lundblad and first author and graduate student Timothy Tucey conducted their studies in the yeast Saccharomyces cerevisiae, the same yeast used to make wine and bread. Previously, Lundblad’s group used this simple single-celled organism to reveal numerous insights about telomerase and lay the groundwork for guiding similar findings in human cells.

“We wanted to be able to study each component of the telomerase complex but that turned out to not be a simple task,” Tucey said. Tucey developed a strategy that allowed him to observe each component during cell growth and division at very high resolution, leading to an unanticipated set of discoveries into how–and when–this telomere-dedicated machine puts itself together.

Every time a cell divides, its entire genome must be duplicated. While this duplication is going on, Tucey discovered that telomerase sits poised as a “preassembly” complex, missing a critical molecular subunit. But when the genome has been fully duplicated, the missing subunit joins its companions to form a complete, fully active telomerase complex, at which point telomerase can replenish the ends of eroding chromosomes and ensure robust cell division.

Surprisingly, however, Tucey and Lundblad showed that immediately after the full telomerase complex has been assembled, it rapidly disassembles to form an inactive “disassembly” complex — essentially flipping the switch into the “off” position. They speculate that this disassembly pathway may provide a means of keeping telomerase at exceptionally low levels inside the cell. Although eroding telomeres in normal cells can contribute to the aging process, cancer cells, in contrast, rely on elevated telomerase levels to ensure unregulated cell growth. The “off” switch discovered by Tucey and Lundblad may help keep telomerase activity below this threshold.