Posts about cell

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.

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.

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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?

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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.

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.

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2009 Nobel Prize in Chemistry: the Structure and Function of the Ribosome

graphic image of the components of a cellCross section of a cell by the Royal Swedish Academy of Sciences. A ribosome is about 25 nanometters (a millionth of a millimeter) in size. A cell contains tens of thousands of ribosomes.

The Nobel Prize in Chemistry for 2009 awards studies of one of life’s core processes: the ribosome’s translation of DNA information into life. Ribosomes produce proteins, which in turn control the chemistry in all living organisms. As ribosomes are crucial to life, they are also a major target for new antibiotics.

This year’s Nobel Prize in Chemistry awards Venkatraman Ramakrishnan, Thomas A. Steitz and Ada E. Yonath for having showed what the ribosome looks like and how it functions at the atomic level. All three have used a method called X-ray crystallography to map the position for each and every one of the hundreds of thousands of atoms that make up the ribosome.

Inside every cell in all organisms, there are DNA molecules. They contain the blueprints for how a human being, a plant or a bacterium, looks and functions. But the DNA molecule is passive. If there was nothing else, there would be no life.

The blueprints become transformed into living matter through the work of ribosomes. Based upon the information in DNA, ribosomes make proteins: oxygen-transporting haemoglobin, antibodies of the immune system, hormones such as insulin, the collagen of the skin, or enzymes that break down sugar. There are tens of thousands of proteins in the body and they all have different forms and functions. They build and control life at the chemical level.

Related: The Nobel Prize in Chemistry 20082007 Nobel Prize in Chemistry2006 Nobel Prize in Chemistryposts on chemistrybasic research posts

Details from the Nobel Prize site (which continues to do a great job providing scientific information to the public openly).
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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.

Related: Nobel Prize in Physiology or Medicine 20082007 Nobel Prize in Physiology or Medicine2006 Nobel Prize in Physiology or Medicine

Webcast of Dr. Elizabeth Blackburn speaking at Google:
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Making Embryonic Stem Cells

photo of Junying Yuphoto of Junying Yu, an assistant scientist with the University of Wisconsin-Madison by Bryce Richter, 2007.

Holy Grail of stem cell research within reach by Mark Johnson

It was time to test the 14 genes she had selected as the best candidates to reprogram a cell.

Using viruses to deliver the genes, she inserted all 14 at once into human cells. On the morning of July 1, 2006, Yu arrived at the lab and examined the culture dishes. Her eyes focused on a few colonies, each resembling a crowded city viewed from space. They looked like embryonic stem cells.

Cells must pass certain tests. They must multiply for weeks while remaining in their delicate, primitive state. When they are allowed to develop, they must turn into all the other cell types.

Bad things happen. Cells develop too soon. Cells die. There is no “aha!” moment, Thomson has said, only stress. He looked at the colonies and suppressed any excitement. He told Yu, essentially: OK, well get back to me in a couple of weeks.

In the fall of 2006, Yu was preparing to whittle down her list of genes when she fell ill. The pain in her gut was awful. She struggled to eat. Her doctor thought it was a stomach flu. Instead, in late October, Yu’s appendix burst. She was laid up for a month. When she returned to the lab, the problem with the culture medium struck again.

Not until January 2007 was she able to begin narrowing the list of genes. She spent several months testing subsets of them, finally arriving at four. Two, Oct4 and Sox2, were “Yamanaka factors,” the name given to the genes the Japanese scientist had used to reprogram mouse cells. Two, Nanog and Lin28, were not.

Using a virus to deliver the four genes, she reprogrammed a line of fetal cells, then repeated the experiments with more mature cells. Although the process was inefficient, succeeding with only a small fraction of cells, it did work.

Dr. Junying Yu, an American trained scientist who entered the US as a foreign student from China. Which is somewhat ironic given the movement of USA based stem cell researches to China. Great article showing the process of scientific inquiry.

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Social Amoeba

Amoebic Morality by Carol Otte

At first their behavior might seem odd; to gather together in the face of starvation surely ought to end in cannibalism or death. Not so, for they are capable of an extraordinary and rare transformation. The amoebas set aside their lives as individuals and join ranks to form a new multicellular entity. Not all the amoebas will survive this cooperative venture, however. Some will sacrifice themselves to help the rest find a new life elsewhere.

These astonishing creatures are Dictyostelium discoideum, and they are a member of the slime mold family. They are also known as social amoebas. Aside from the novelty value of an organism that alternates between unicellular and multicellular existence, D. discoideum is highly useful in several areas of research. Among other things, this organism offers a stellar opportunity to study cell communication, cell differentiation, and the evolution of altruism.

In response to the cAMP distress call, up to one hundred thousand of the amoebas assemble. They first form a tower, which eventually topples over into an oblong blob about two millimeters long. The identical amoebas within this pseudoplasmodium– or slug– begin to differentiate and take on specialized roles.

Another cool example of how life has evolved novel solutions to perpetuate genes.

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How Antibiotics Kill Bacteria

How Antibiotics Kill Bacteria

Since the first antibiotics reached the pharmacy in the 1940s, researchers discovered that they target various pieces of machinery in bacterial cells, disrupting the bacteria’s ability to build new proteins, DNA, or cell wall. But these effects alone do not cause death, and a complete explanation of what actually kills bacteria after they are exposed to antibiotics has eluded scientists.

The group found that all bactericidal antibiotics, regardless of their initial targets inside bacteria, caused E. coli to produce unstable chemicals called hydroxyl radicals. These compounds react with proteins, DNA, and lipids inside cells, causing widespread damage and rapid death for the bacteria.

With the results of these two experiments, the researchers were able to identify three major processes implicated in gentamicin-induced cell death: protein transport, a stress response triggered by abnormal proteins in the cell membrane, and a metabolic stress response.

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How Cells Age

How Cells Age

A new study by Harvard Medical School researchers reveals that the biochemical mechanism that makes yeast grow old has a surprising parallel in mice, suggesting it may be a universal cause of aging in all organisms.

In young organisms, SIRT1 effectively doubles as a gene-expression regulator and a DNA repairer. But when DNA damage accumulates—as it does with age—SIRT1 becomes too busy fixing broken DNA to keep the expression of hundreds of genes in check. This process is so similar to what happens in aging yeast that its discoverers believe it may represent a universal mechanism of aging.

Harvard researchers gain new insight into aging

Aging may be a case of neglect — an absentee landlord at the cellular level that allows gene activity to go awry, according to a study published today.

Scientists have long known that aging causes gene expression to change, and DNA damage to accumulate. But now, research led by Harvard Medical School scientists explains the connection between the two processes in mammals.

The paper, published in the journal Cell, found that a multi-tasking protein called SIRT1 that normally acts as guardian of the genome gets dragged away to DNA fix-it jobs. When the protein abandons its normal post to work as a genetic handyman, order unravels elsewhere in the cell. Genes that are normally under its careful watch begin to flip on.

“What this paper actually implies is that aspects of aging may be reversible,” said David Sinclair, a Harvard Medical School biologist who led the research. “It sounds crazy, but in principle it should be possible to restore the youthful set of genes, the patterns that are on and off.”

The study is just the latest to draw yet more attention to sirtuins, proteins involved in the aging process

Aging is fascinating. By and large people just accept it. We see it happen to those all around us, without exception. But what causes biological aging? It is an interesting area of research.

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Single-Celled Giant Provides New Early-Evolution Perspective

Discovery of Giant Roaming Deep Sea Protist Provides New Perspective on Animal Evolution
Biologist Mikhail “Misha” Matz and his colleagues recently discovered the grape-sized protists and their complex tracks on the ocean floor near the Bahamas. DNA analysis confirmed that the giant protist found by Matz and his colleagues in the Bahamas is Gromia sphaerica, a species previously known only from the Arabian Sea.

Matz says the protists probably move by sending leg-like extensions, called pseudopodia, out of their cells in all directions. The pseudopodia then grab onto mud in one direction and the organism rolls that way, leaving a track. Hr says the giant protists’ bubble-like body design is probably one of the planet’s oldest macroscopic body designs, which may have existed for 1.8 billion years.

“I personally think now that the whole Precambrian may have been exclusively the reign of protists,” says Matz. “Our observations open up this possible way of interpreting the Precambrian fossil record.”

He says the appearance of all the animal body plans during the Cambrian explosion might not just be an artifact of the fossil record. There are likely other mechanisms that explain the burst-like origin of diverse multicellular life forms.

Single-Celled Giant Upends Early Evolution

Slowly rolling across the ocean floor, a humble single-celled creature is poised to revolutionize our understanding of how complex life evolved on Earth.

A distant relative of microscopic amoebas, the grape-sized Gromia sphaerica was discovered once before, lying motionless at the bottom of the Arabian Sea. But when Mikhail Matz of the University of Texas at Austin and a group of researchers stumbled across a group of G. sphaerica off the coast of the Bahamas, the creatures were leaving trails behind them up to 50 centimeters (20 inches) long in the mud.

The trouble is, single-celled critters aren’t supposed to be able to leave trails. The oldest fossils of animal trails, called ‘trace fossils’, date to around 580 million years ago, and paleontologists always figured they must have been made by multicellular animals with complex, symmetrical bodies.

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Exploring the Signaling Pathways of Cells

New probe may help untangle cells’ signaling pathways

MIT researchers have designed a new type of probe that can image thousands of interactions between proteins inside a living cell, giving them a tool to untangle the web of signaling pathways that control most of a cell’s activities.

“We can use this to identify new protein partners or to characterize existing interactions. We can identify what signaling pathway the proteins are involved in and during which phase of the cell cycle the interaction occurs,” said Alice Ting, the Pfizer-Laubach Career Development Assistant Professor of Chemistry and senior author of a paper describing the probe published online June 27 by the Journal of the American Chemical Society.

The new technique allows researchers to tag proteins with probes that link together like puzzle pieces if the proteins interact inside a cell. The probes are derived from an enzyme and its peptide substrate. If the probe-linked proteins interact, the enzyme and substrate also interact, which can be easily detected.

To create the probes, the researchers used the enzyme biotin ligase and its target, a 12-amino-acid peptide.

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