Tag Archives: Life Science

Engineering: Cellphone Microscope

UCLA Professor Aydogan Ozcan‘s invention (LUCAS) enables rapid counting and imaging of cells without using any lenses even within a working cell phone device. He placed cells directly on the imaging sensor of a cell phone. The imaging sensor captures a holographic image of the cells containing more information than a conventional microscope. The CelloPhone received a Wireless Innovations Award from Vodafone

a wireless health monitoring technology that runs on a regular cell-phone would significantly impact the global fight against infectious diseases in resource poor settings such as in Africa, parts of India, South-East Asia and South America.

The CelloPhone Project aims to develop a transformative solution to these global challenges by providing a revolutionary optical imaging platform that will be used to specifically analyze bodily fluids within a regular cell phone. Through wide-spread use of this innovative technology, the health care services in the developing countries will significantly be improved making a real impact in the life quality and life expectancy of millions.
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For most bio-medical imaging applications, directly seeing the structure of the object is of paramount importance. This conventional way of thinking has been the driving motivation for the last few decades to build better microscopes with more powerful lenses or other advanced imaging apparatus. However, for imaging and monitoring of discrete particles such as cells or bacteria, there is a much better way of imaging that relies on detection of their shadow signatures. Technically, the shadow of a micro-object can be thought as a hologram that is based on interference of diffracted beams interacting with each cell. Quite contrary to the dark shadows that we are used to seeing in the macro-world (such as our own shadow on the wall), micro-scale shadows (or transmission holograms) contain an extremely rich source of quantified information regarding the spatial features of the micro-object of interest.

By making use of this new way of thinking, unlike conventional lens based imaging approaches, LUCAS does not utilize any lenses, microscope-objectives or other bulk optical components, and it can immediately monitor an ultra-large field of view by detecting the holographic shadow of cells or bacteria of interest on a chip. The holographic diffraction pattern of each cell, when imaged under special conditions, is extremely rich in terms of spatial information related to the state of the cell or bacteria. Through advanced signal processing tools that are running at a central computer station, the unique texture of these cell/bacteria holograms will enable highly specific and accurate medical diagnostics to be performed even in resource poor settings by utilizing the existing wireless networks.

This is another great example of engineers creating technologically appropriate solutions.

The Only Known Cancerless Animal

Unlike any other mammal, naked mole rate communities consist of queens and workers more reminiscent of bees than rodents. Naked mole rats can live up to 30 years, which is exceptionally long for a small rodent. Despite large numbers of naked mole-rats under observation, there has never been a single recorded case of a mole rat contracting cancer, says Gorbunova. Adding to their mystery is the fact that mole rats appear to age very little until the very end of their lives.

The mole rat’s cells express p16, a gene that makes the cells “claustrophobic,” stopping the cells’ proliferation when too many of them crowd together, cutting off runaway growth before it can start. The effect of p16 is so pronounced that when researchers mutated the cells to induce a tumor, the cells’ growth barely changed, whereas regular mouse cells became fully cancerous.

“It’s very early to speculate about the implications, but if the effect of p16 can be simulated in humans we might have a way to halt cancer before it starts.” says Vera Gorbunova, associate professor of biology at the University of Rochester and lead investigator on the discovery.

In 2006, Gorbunova discovered that telomerase—an enzyme that can lengthen the lives of cells, but can also increase the rate of cancer—is highly active in small rodents, but not in large ones.

Until Gorbunova and Seluanov’s research, the prevailing wisdom had assumed that an animal that lived as long as we humans do needed to suppress telomerase activity to guard against cancer. Telomerase helps cells reproduce, and cancer is essentially runaway cellular reproduction, so an animal living for 70 years has a lot of chances for its cells to mutate into cancer, says Gorbunova. A mouse’s life expectancy is shortened by other factors in nature, such as predation, so it was thought the mouse could afford the slim cancer risk to benefit from telomerase’s ability to speed healing.

While the findings were a surprise, they revealed another question: What about small animals like the common grey squirrel that live for 24 years or more? With telomerase fully active over such a long period, why isn’t cancer rampant in these creatures?

Engineered Circuits That can Count Cellular Events

Engineered circuits can count cellular events by Anne Trafton

MIT and Boston University engineers have designed cells that can count and “remember” cellular events, using simple circuits in which a series of genes are activated in a specific order.
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The first counter, dubbed the RTC (Riboregulated Transcriptional Cascade) Counter, consists of a series of genes, each of which produces a protein that activates the next gene in the sequence.

With the first stimulus — for example, an influx of sugar into the cell — the cell produces the first protein in the sequence, an RNA polymerase (an enzyme that controls transcription of another gene). During the second influx, the first RNA polymerase initiates production of the second protein, a different RNA polymerase.

The number of steps in the sequence is, in theory, limited only by the number of distinct bacterial RNA polymerases. “Our goal is to use a library of these genes to create larger and larger cascades,” said Lu.

The counter’s timescale is minutes or hours, making it suitable for keeping track of cell divisions. Such a counter would be potentially useful in studies of aging.

The RTC Counter can be “reset” to start counting the same series over again, but it has no way to “remember” what it has counted. The team’s second counter, called the DIC (DNA Invertase Cascade) Counter, can encode digital memory, storing a series of “bits” of information.

The process relies on an enzyme known as invertase, which chops out a specific section of double-stranded DNA, flips it over and re-inserts it, altering the sequence in a predictable way.

The DIC Counter consists of a series of DNA sequences. Each sequence includes a gene for a different invertase enzyme. When the first activation occurs, the first invertase gene is transcribed and assembled. It then binds the DNA and flips it over, ending its own transcription and setting up the gene for the second invertase to be transcribed next.

When the second stimulus is received, the cycle repeats: The second invertase is produced, then flips the DNA, setting up the third invertase gene for transcription. The output of the system can be determined when an output gene, such as the gene for green fluorescent protein, is inserted into the cascade and is produced after a certain number of inputs or by sequencing the cell’s DNA.

This circuit could in theory go up to 100 steps (the number of different invertases that have been identified). Because it tracks a specific sequence of stimuli, such a counter could be useful for studying the unfolding of events that occur during embryonic development, said Lu.

Other potential applications include programming cells to act as environmental sensors for pollutants such as arsenic. Engineers would also be able to specify the length of time an input needs to be present to be counted, and the length of time that can fall between two inputs so they are counted as two events instead of one.

Dennis Bray Podcast on Microbes As Computers

Carl Zimmer interviews Dennis Bray in an interesting podcast:

Dennis Bray is an active professor emeritus in both the Department of Physiology and Department of Neuroscience at the University of Cambridge. He studies the behavior of microbes–how they “decide” where to swim, when to divide, and how best to manage the millions of chemical reactions taking place inside their membranes. For Bray, microbes are tiny, living computers, with genes and proteins serving the roles of microprocessors.

2009 Nobel Prize in Physiology or Medicine

This year’s Nobel Prize in Physiology or Medicine is awarded to three scientists who have solved a major problem in biology: how the chromosomes can be copied in a complete way during cell divisions and how they are protected against degradation. The Nobel Laureates have shown that the solution is to be found in the ends of the chromosomes – the telomeres – and in an enzyme that forms them – telomerase.

The long, thread-like DNA molecules that carry our genes are packed into chromosomes, the telomeres being the caps on their ends. Elizabeth Blackburn and Jack Szostak discovered that a unique DNA sequence in the telomeres protects the chromosomes from degradation. Carol Greider and Elizabeth Blackburn identified telomerase, the enzyme that makes telomere DNA. These discoveries explained how the ends of the chromosomes are protected by the telomeres and that they are built by telomerase.

If the telomeres are shortened, cells age. Conversely, if telomerase activity is high, telomere length is maintained, and cellular senescence is delayed. This is the case in cancer cells, which can be considered to have eternal life. Certain inherited diseases, in contrast, are characterized by a defective telomerase, resulting in damaged cells. The award of the Nobel Prize recognizes the discovery of a fundamental mechanism in the cell, a discovery that has stimulated the development of new therapeutic strategies.

Scientists began to investigate what roles the telomere might play in the cell. Szostak’s group identified yeast cells with mutations that led to a gradual shortening of the telomeres. Such cells grew poorly and eventually stopped dividing. Blackburn and her co-workers made mutations in the RNA of the telomerase and observed similar effects in Tetrahymena. In both cases, this led to premature cellular ageing – senescence. In contrast, functional telomeres instead prevent chromosomal damage and delay cellular senescence. Later on, Greider’s group showed that the senescence of human cells is also delayed by telomerase. Research in this area has been intense and it is now known that the DNA sequence in the telomere attracts proteins that form a protective cap around the fragile ends of the DNA strands.

Many scientists speculated that telomere shortening could be the reason for ageing, not only in the individual cells but also in the organism as a whole. But the ageing process has turned out to be complex and it is now thought to depend on several different factors, the telomere being one of them. Research in this area remains intense.

The 3 awardees are citizens of the USA; two were born elsewhere.
Read more about their research at the Nobel Prize web site.

Molecular biologist Elizabeth Blackburn–one of Time magazine’s 100 “Most Influential People in the World” in 2007–made headlines in 2004 when she was dismissed from the President’s Council on Bioethics after objecting to the council’s call for a moratorium on stem cell research and protesting the suppression of relevant scientific evidence in its final report.

Webcast of Dr. Elizabeth Blackburn speaking at Google:
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Bacteria Use Nitric Oxide to Resist Antibiotics

Scientists Discover Mechanism to Make Existing Antibiotics More Effective at Lower Doses

Eliminating this NO[nitric oxide]-mediated bacterial defense renders existing antibiotics more potent at lower, less toxic, doses. With infectious diseases the major cause of death worldwide, the study paves the way for new ways of combating bacteria that have become antibiotic resistant.

NO is a small molecule composed of one atom of oxygen and one of nitrogen. It was known as a toxic gas and air pollutant until 1987, when it was first shown to play a physiological role in mammals, for which a Nobel Prize was later awarded. NO has since been found to take part in an extraordinary range of activities including learning and memory, blood pressure regulation, penile erection, digestion and the fighting of infection and cancer. A few years ago, the Nudler’s group from NYU demonstrated that bacteria mobilize NO to defend against the oxidative stress. The new study from the same group supports the radical idea that many antibiotics cause the oxidative stress in bacteria, often resulting in their death, whereas NO counters this effect. This work suggests scientists could use commercially available inhibitors of NO-synthase, an enzyme producing NO in bacteria and humans, to make antibiotic resistant bacteria like MRSA and ANTHRAX more sensitive to available drugs during acute infection.
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The study by Nudler and his colleagues was funded by a 2006 Pioneer Award from the National Institutes of Health in Bethesda, Maryland. The Pioneer Award, a $2.5 million grant over five years, is designed to support individual scientists of exceptional creativity who propose pioneering and possibly transforming approaches to major challenges in biomedical and behavioral research.

Norman E. Borlaug 1914-2009

The Father Of the Green Revolution

Norman E. Borlaug, 95, an American plant pathologist who won the Nobel Peace Prize in 1970 for starting the “Green Revolution” that dramatically increased food production in developing nations and saved countless people from starvation, died Saturday at his home in Dallas.

“More than any other single person of this age, he has helped provide bread for a hungry world,” the Nobel committee said in honoring him. “Dr. Borlaug has introduced a dynamic factor into our assessment of the future and its potential.”
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In his lecture accepting the Nobel Prize, he said an adequate supply of food is “the first component of social justice. . . . Otherwise there will be no peace.”
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In 1977, Dr. Borlaug received the Medal of Freedom, the highest civilian honor of the U.S. government.

Billions Served: Norman Borlaug interviewed by Ronald Bailey

As a matter of fact, Mother Nature has crossed species barriers, and sometimes nature crosses barriers between genera–that is, between unrelated groups of species. Take the case of wheat. It is the result of a natural cross made by Mother Nature long before there was scientific man. Today’s modern red wheat variety is made up of three groups of seven chromosomes, and each of those three groups of seven chromosomes came from a different wild grass. First, Mother Nature crossed two of the grasses, and this cross became the durum wheats, which were the commercial grains of the first civilizations spanning from Sumeria until well into the Roman period. Then Mother Nature crossed that 14-chromosome durum wheat with another wild wheat grass to create what was essentially modern wheat at the time of the Roman Empire.

Durum wheat was OK for making flat Arab bread, but it didn’t have elastic gluten. The thing that makes modern wheat different from all of the other cereals is that it has two proteins that give it the doughy quality when it’s mixed with water. Durum wheats don’t have gluten, and that’s why we use them to make spaghetti today. The second cross of durum wheat with the other wild wheat produced a wheat whose dough could be fermented with yeast to produce a big loaf. So modern bread wheat is the result of crossing three species barriers, a kind of natural genetic engineering.
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I see no difference between the varieties carrying a BT gene or a herbicide resistance gene, or other genes that will come to be incorporated, and the varieties created by conventional plant breeding. I think the activists have blown the health risks of biotech all out of proportion.
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the data that’s put out by the World Health Organization and [the U.N.’s Food and Agriculture Organization], there are probably 800 million people who are undernourished in the world. So there’s still a lot of work to do.

I am a bit more cautious about supporting genetic engineering in our food supply but I agree with him that we need to remain focused on the lives of hundreds of millions of hungry people (which is far too often ignored). I am worried about the risks to the environment and human health. I am also worried about the concentration of food plants in a greatly reduced genetic varieties that are more productive in general but increase the risks of massive food failures (due to limited genetic varieties).

40 New Species Found in Papua New Guinea

The rat is not afraid of humans, which could make it vulnerable. Photo by the BBC.

Yet another discovery of dozens of new species has been made. The rat that’s the size of a cat: 40 new species in ‘lost world’ at a remote volcano in Papua New Guinea.

In the kilometre-deep crater of Mount Bosavi, they found a habitat teeming with life which has evolved in isolation since the volcano last erupted 200,000 years ago.

Among the new species was the the Bosavi Woolly Rat. One of the biggest rats in the world, it measures just over 32 inches from nose to tail and weighs 3lb. The silvery grey mammal has dense fur and its teeth suggest it has a largely vegetarian diet and probably builds nests in tree hollows or underground.
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It is estimated that along with the giant rat and cuscus the expedition found about 16 species of frogs, one species of gecko, at least three species of fish, at least 20 of insects and spiders and possibly one new species of bat.
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Further evidence of the rich wildlife of the tropical location came with the discovery of the Bosavi Silky Cuscus. This animal, which resembles a small bear, is a marsupial that lives up in trees, feeding on fruits and leaves.

Weighing in at some 4.5lb, it has thick silky fur adapted for the mountain environment in which it lives. Dr Helgen has identified it as a new subspecies in the group of strange marsupials known as cuscuses.
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The habitat in the area is currently regarded as pristine, but less than 20 miles to the south of Mount Bosavi extensive logging operations are happening.

Researchers Work to Protect Bats Against Deadly Disease

Researchers work to protect Wisconsin bats against deadly disease

Redell, who studies bats for the Department of Natural Resources, lives every day now with the threat of a disease called white-nose syndrome hanging over his head. The disease, though not yet in Wisconsin, has killed more than 90 percent of the cave bats in Eastern states such as New York and Vermont. Experts predict it could make its way to Wisconsin, with its eight species and hundreds of thousands of bats, in as little as two years.
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One female little brown bat – with a body less than the length of your thumb – can eat its body weight in insects in one evening, Redell said. Such is the insect-hunting prowess of the bats that they are thought to save farmers billions of dollars in crop losses, according to Sheryl L. Ducummon, with Bat Conservation International.

In a recent scientific article on the ecological and economic importance of bats, Ducummon reported that, in one summer, the 150 bats in an average colony of big brown bats can conservatively eat 38,000 cucumber beetles, which attack corn and other farm crops. Damage from the beetle and their larvae cost corn farmers as much as $1 billion a year.

The loss of such an insect-eating force could be devastating, Redell said. The approximate 1 million bats that have already died of white-nose syndrome in the last three years on the East Coast would have eaten 700,000 tons of insects were they still hunting the night skies, he said.

Bats perform other important tasks, too. Several Western species serve crucial roles as pollinators for desert plants such as agave and as seed dispersers for dozens of species of cacti.
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“I mean, this is like a mouse that flies, but it has the predatory capabilities of a polar bear,” Blehert said. “They are physically adapted to command the night sky. You’re talking about a little thing with a body less than half the size of your thumb whose heartbeat can get up to 1,000 beats a minute when they are flying but that can slow when they are hibernating in the winter to 4 beats a minute. And they live 20 to 25 years!”

Bats really are amazing and very valuable animals.

Honeybees Warn Others of Risks

Honeybees warn of risky flowers

They trained honeybees to visit two artificial flowers containing the same amount and concentration of food. They left one flower untouched, making it a “safe” food source for the bees.

On the other flower, they placed the bodies of two dead bees, so they were visible to arriving insects, but would not interfere with their foraging. They then recorded whether and how the bees performed a waggle dance on their return to other members of the hive colony.

On average, bees returning from safe flowers performed 20 to 30 times more waggle runs that bees returning from dangerous flowers.

That shows that the bees recognise that certain flowers carry a higher risk of being killed or eaten by predators, such as crab spiders or other spider species that ambush visiting bees.