Science Daily — Students of the evolution of social behavior got a big boost with the publication of the newly sequenced honeybee genome in October 2006. The honeybee (Apis mellifera) belongs to the rarified cadre of insects that pool resources, divide tasks, and communicate with each other in highly structured colonies. Understanding how this advanced state of organization evolved from a solitary lifestyle has been an enduring question in biology.
A honeybee gene originally used in egg production has become an important behavioral modulator and a timekeeper of social life. (Credit: Siri-Christine Seehuus / PLoS Biology)
In a new study published in PLoS Biology, Mindy Nelson, Kate Ihle, Gro Amdam, and colleagues reveal one possible path to community by showing that a single gene controls multiple traits related to honeybee sociability. First characterized for its role in reproduction, the gene, vitellogenin, is widely found in egg-laying insects, which depend on it for egg cell development.
A honeybee's lot in life depends on its age, gender, and caste. Reproduction falls to the queen and drones, while essentially infertile females, the workers, perform all the other duties required to support the colony. As young adults, workers tend larvae and perform assorted tasks in the hive. After about three weeks, they switch from domestic chores to foraging, and eventually specialize in pollen or nectar collection.
Scientists began to suspect that the protein synthesized from the vitellogenin gene--vitellogenin--might affect these social life history traits in honeybees as it became clear that the protein supported an array of functions not directly linked to egg-laying. For example, sterile workers synthesize vitellogenin to make the royal jelly they feed larvae. It can also prolong the lifespan of both workers and the queen by reducing oxidative stress.
As bees undergo the complex behavioral shift demanded by the change in job description, their physiology changes too: they have higher levels of juvenile hormone and lower levels of vitellogenin. It was speculated that these two physiological factors repress each other to affect the bees' behavior, with vitellogenin repressing juvenile hormone in younger bees to inhibit the shift from nest to field, and juvenile hormone repressing vitellogenin in bees that have switched to foraging to ensure that they stay true to their task and do not revert to nest jobs. In a previous study, the researchers also proposed that changes in vitellogenin gene expression early in life could foster the selective behavior that creates the division of labor between pollen and nectar specialists.
To test these proposed roles of vitellogenin in coordinating the social life of the honeybee, Nelson et al. inhibited the expression of the vitellogenin gene with RNA interference (RNAi). This gene-silencing tool introduces a double-stranded RNA (dsRNA) product whose sequence is complementary to a target gene, thereby setting off a series of events that ultimately "knocks down" the target gene. The researchers injected a vitellogenin dsRNA preparation into the abdomen of a subset of bees and compared their behavior and lifespan to a control group. (The control group also received a dsRNA treatment designed to mimic the stress of experimental handling without affecting gene expression.) The bees' vitellogenin levels were monitored at 10 days, 15 days, and 20 days old to make sure the RNAi effects persisted.
Compared to controls, dsRNA-treated bees had consistently lower levels of vitellogenin protein. These vitellogenin "knockdowns" started foraging at a younger age than controls--confirming that vitellogenin affects workers' occupational fate by repressing the shift from domestic to foraging tasks. The foragers also showed a preference for nectar, in keeping with evidence that workers genetically predisposed toward nectar have lower vitellogenin levels before leaving the nest, while those predisposed toward pollen have higher levels. But more directly, the researchers argue, these results show that vitellogenin controls social foraging specialization. What's more, the vitellogenin-deficient bees died earlier than the controls, demonstrating the protein's influence on honeybee longevity.
Altogether, these results demonstrate that vitellogenin regulates the organizational structure of honeybee society by influencing workers' division of labor and foraging preference. Vitellogenin, the researchers conclude, controls not only when bees start foraging and how long they live, but what they forage. Higher levels early in life favor pollen; lower levels favor nectar. Since current methods cannot yet distinguish the effects of vitellogenin from those of juvenile hormone, the researchers argue that the two physiological factors should be considered as partners in mediating task assignment and specialization. Since this partnership is uncommon in insects, it suggests that social behavior in honeybees emerged from a makeover of relations between vitellogenin and juvenile hormone. It also bolsters the notion that factors normally in control of female reproduction can lay the foundation for the transition from solitary life to complex social behavior.
Citation: Nelson CM, Ihle KE, Fondrk MK, Page RE Jr, Amdam GV (2007) The gene vitellogenin has multiple coordinating effects on social organization. PLoS Biol 5(3): e62. doi:10.1371/journal.pbio.0050062.
Source: Public Library of Science Date: March 18, 2007
2007-03-12
Fruit Flies May Pave Way To New Treatments For Age-related Heart Disease
Science Daily — The tiny Drosophila fruit fly may pave the way to new methods for studying and finding treatments for heart disease, the leading cause of death in industrialized countries, according to a collaborative study by the Burnham Institute for Medical Research, UC San Diego (UCSD) and the University of Michigan.
The study reports that mutations in a molecular channel found in heart muscle cell membranes caused arrhythmias similar to those that are found in humans, suggesting that understanding how this channel's activity is controlled in the cell could lead to new heart disease treatments. Led by Burnham's Professor Rolf Bodmer, Ph.D., and Staff Scientist Karen Ocorr, Ph.D., these new results,are to be published in Proceedings of the National Academy of Sciences.
"This study shows that the Drosophila heart can be a model for the human heart," said Burnham researcher Bodmer. "Fly hearts have many ion channels that also are present in human hearts, making it suitable to extend mechanistic insight found in the fly hearts to human heart function."
The researchers focused on a membrane channel in the tiny Drosophila heart called KCNQ. This membrane channel, found in flies and humans, regulates the heart's ability to return to a relaxed state after beating. This ability is crucial to healthy cardiac functions, and the inability to return to a relaxed state results in arrhythmias, which can lead to more serious heart disease and sudden death. In both flies and humans, cardiac arrhythmia and dysfunctions become more common with age.
The team found that mutations in the fly's single KCNQ gene led to severe arrhythmias that would be immediately fatal to a human, but not in this insect that does not rely on the heart for oxygen supply. Hearts in young flies with the KCNQ mutation exhibited prolonged heart contractions and irregular beats seen usually in older flies (and older people). To enable their study of the fly heart, the researchers created new methods to dissect the hearts, and quantify heart contractility and other functions by using a movie camera to capture fly's cardiac activity.
"We started with Nick Reeves and James Posakony at UCSD, who originally made the mutant KCNQ fly for a different purpose. We then studied these mutants with the new heart function assays that Ocorr was developing in my lab. Subsequently, we worked with Martin Fink and Wayne Giles at UCSD to develop a computer program that would allow the automated quantification of heart beat parameters and arrhythmias from the video images," Bodmer said. In addition, collaborations with H.S. Vincent Chen at Burnham and Soichiro Yasuda and Joseph Metzger of the University of Michigan enabled measuring the fly's electrocardiogram (ECG) and heartbeat force and tension, respectively.
"We now have a lot of methods to precisely assess heart function in the fly, which augments its usefulness as a genetic model for studying cardiac function," said Ocorr, who conducted most of these studies.
The study points to KCNQ as a major factor in heart disease, but Bodmer warns that much more research is needed to use it alone as a drug target. "The fact that heart functions deteriorate in the mutant flies during aging suggests that there are other channels and genes that contribute to cardiac aging," he said. "We need to better understand the regulatory systems that control the level and activity of known cardiac channels and other unknown factors involved in coordinated heart muscle contraction."
In fact, the researchers are now looking at identifying other genes that regulate KCNQ channel function and heart physiology, and--thanks to the short lifespan of Drosophila --can look at the effects of aging, which is much harder to do in mammals with a relatively long lifespan.
"There's an amazing conservation of genes between flies and humans," Bodmer said. "We can now look at how heart function ages in a realistic timeframe."
In addition to first author Ocorr, and contributions from collaborators Reeves, Fink, Chen, Yasuda, Posakony, Giles and Metzger, Bodmer's colleagues included Robert Wessells and Takeshi Akasaka at Burnham.
"The collaborative spirit at Burnham", said Bodmer, "greatly facilitated interactions among the researchers that brought this multidisciplinary study to fruition".
This work was supported by grants from the National Institutes of Health, as well as private support to H.S. Vincent Chen at Burnham from the American College of Cardiology Foundation.
Note: This story has been adapted from a news release issued by Burnham Institute.
Source:Burnham InstituteDate:March 12, 2007
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The study reports that mutations in a molecular channel found in heart muscle cell membranes caused arrhythmias similar to those that are found in humans, suggesting that understanding how this channel's activity is controlled in the cell could lead to new heart disease treatments. Led by Burnham's Professor Rolf Bodmer, Ph.D., and Staff Scientist Karen Ocorr, Ph.D., these new results,are to be published in Proceedings of the National Academy of Sciences.
"This study shows that the Drosophila heart can be a model for the human heart," said Burnham researcher Bodmer. "Fly hearts have many ion channels that also are present in human hearts, making it suitable to extend mechanistic insight found in the fly hearts to human heart function."
The researchers focused on a membrane channel in the tiny Drosophila heart called KCNQ. This membrane channel, found in flies and humans, regulates the heart's ability to return to a relaxed state after beating. This ability is crucial to healthy cardiac functions, and the inability to return to a relaxed state results in arrhythmias, which can lead to more serious heart disease and sudden death. In both flies and humans, cardiac arrhythmia and dysfunctions become more common with age.
The team found that mutations in the fly's single KCNQ gene led to severe arrhythmias that would be immediately fatal to a human, but not in this insect that does not rely on the heart for oxygen supply. Hearts in young flies with the KCNQ mutation exhibited prolonged heart contractions and irregular beats seen usually in older flies (and older people). To enable their study of the fly heart, the researchers created new methods to dissect the hearts, and quantify heart contractility and other functions by using a movie camera to capture fly's cardiac activity.
"We started with Nick Reeves and James Posakony at UCSD, who originally made the mutant KCNQ fly for a different purpose. We then studied these mutants with the new heart function assays that Ocorr was developing in my lab. Subsequently, we worked with Martin Fink and Wayne Giles at UCSD to develop a computer program that would allow the automated quantification of heart beat parameters and arrhythmias from the video images," Bodmer said. In addition, collaborations with H.S. Vincent Chen at Burnham and Soichiro Yasuda and Joseph Metzger of the University of Michigan enabled measuring the fly's electrocardiogram (ECG) and heartbeat force and tension, respectively.
"We now have a lot of methods to precisely assess heart function in the fly, which augments its usefulness as a genetic model for studying cardiac function," said Ocorr, who conducted most of these studies.
The study points to KCNQ as a major factor in heart disease, but Bodmer warns that much more research is needed to use it alone as a drug target. "The fact that heart functions deteriorate in the mutant flies during aging suggests that there are other channels and genes that contribute to cardiac aging," he said. "We need to better understand the regulatory systems that control the level and activity of known cardiac channels and other unknown factors involved in coordinated heart muscle contraction."
In fact, the researchers are now looking at identifying other genes that regulate KCNQ channel function and heart physiology, and--thanks to the short lifespan of Drosophila --can look at the effects of aging, which is much harder to do in mammals with a relatively long lifespan.
"There's an amazing conservation of genes between flies and humans," Bodmer said. "We can now look at how heart function ages in a realistic timeframe."
In addition to first author Ocorr, and contributions from collaborators Reeves, Fink, Chen, Yasuda, Posakony, Giles and Metzger, Bodmer's colleagues included Robert Wessells and Takeshi Akasaka at Burnham.
"The collaborative spirit at Burnham", said Bodmer, "greatly facilitated interactions among the researchers that brought this multidisciplinary study to fruition".
This work was supported by grants from the National Institutes of Health, as well as private support to H.S. Vincent Chen at Burnham from the American College of Cardiology Foundation.
Note: This story has been adapted from a news release issued by Burnham Institute.
Source:Burnham InstituteDate:March 12, 2007
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University of Iowa Researcher Studies Deafness In Fruit Flies, Humans
Researchers Locate Tumor-suppressor Gene In Fruit Flies That Controls Cell Production, Death Fruit Flies And Global Warming: Some Like It Hot
Fly Mutation Suggests Link To Human Brain Disease
'Drunk' Fruit Flies Could Shed Light On Genetic Basis Of Human Alcohol Abuse
2007-03-11
Fruit Fly Insight Could Lead To New Vaccines
Science Daily — The tiny fruit fly has a lot to teach humans. Researchers at the Stanford University School of Medicine have found for the first time that flies' primitive immune systems may develop long-term protection from infection, an ability previously thought impossible for insects.
The findings could have implications for new ways of developing human vaccines, especially for people with compromised immune systems.
The evidence that a fruit fly's immune response can adapt to - or retain memory of - an earlier infection contradicts the long-held dogma that immune memory cannot exist in invertebrates such as insects. Such memory of a specific pathogen, known as adaptation, is supposed to be a hallmark of the higher-level immune system response of humans and other vertebrates.
The Stanford work raises the possibility that humans could make use of this rudimentary immune response if their higher-level system is crippled. "It's a springboard to looking at the immune system in a whole new way," said David Schneider, PhD, assistant professor of microbiology and immunology and senior author of the study, which will be published in the Public Library of Science-Pathogens.
One of the two arms of the immune response in higher organisms is similar to that of flies. This arm is known as innate immunity, and it is thought to be a primitive first-line, nonspecific response to a pathogen "invader." The other arm found in higher organisms is adaptive immunity, which has a memory that retains an internal record of contact with an invader and - employing T and B cells - springs into action once it encounters the same invader again. This adaptive immunity explains why a vaccine provides protection.
"AIDS patients are like fruit flies in the sense that they don't have properly functioning T cells," said Schneider. "If there is anything we could do to make their remaining innate immunity better through adaptation, that would be really helpful."
Harnessing the potential power of adaptation in the innate immune system might also be a boon in the body's defense against bioterrorism or disease pandemics. "The B and T cells of the adaptive immune system take a long time to react," said Schneider. "But you might be able to speed things up if you could snort something up your nose that would make your innate immune system ready to fight."
While inviting novel ways of thinking about future vaccines and treating AIDS patients, the new finding immediately stirs up the field of insect immunology. Existing publications about the fruit fly's immune system explicitly state that it has no memory, and no ability to make specific long-term changes prompted by its exposure to pathogens. Because immune memory was defined as nonexistent, no one ever did the experiment to question whether the fly's immune system could adapt.
Then graduate student Linh Pham arrived in Schneider's lab. She was interested in pushing the boundaries of the assumptions of the innate immune system's limitations.
In the past decade or so, work done on fruit fly immunology has always been done on a fly infected only once - and that's not how things happen outside a lab, where a fly would be continually exposed to microbes. Pham thought to ask what happens when the flies encounter a microbe a second time.
Pham found a bacterium - Streptococcus pneumoniae - that infected the flies but didn't kill all of them. "I liken my work to the first vaccination experiments," said Pham, who is first author of the study. She essentially vaccinated over a million flies, typically doing 7,000 in a day, in numerous experiments. In a key experiment, she injected some flies with killed bacteria and others with just saline solution. She waited a week, then reinjected both groups with what should have been a lethal dose of live bacteria. Then she calculated the percentage of how many survived, compared with the flies that been injected only with saline.
"I didn't think the results would be so clean-cut," she said. Within two days, the second dose killed almost all of the flies that had initially received just saline solution. Those that had been vaccinated lived just as long - about one month - as a separate group that had not been infected.
To ensure it wasn't a fluke of the bacterium she chose, she tested other organisms. She identified a fungus that infects fruit flies in the wild, Beauveria bassiana, that elicited a similar protective effect. "It was really easy to show the adaptation part," she added. "Getting to the mechanism was the complicated part."
In the study, the researchers conclude that a much-studied receptor called Toll is involved, as are other processes. Pham is now teasing apart the finer aspects of how the fruit fly protects itself against S. pneumoniae.
Schneider and Pham said they hope their work encourages the search for a similar adaptive response in the innate immune systems of humans or other vertebrates. "One of the things that I thought was really cool about this work is that it might be a way to develop a vaccine that modulates the innate immune system," said Pham. "Of course, we are cautious about hoping for this."
Note: This story has been adapted from a news release issued by Stanford University Medical Center.
Source:Stanford University Medical Center Date:March 11, 2007
The findings could have implications for new ways of developing human vaccines, especially for people with compromised immune systems.
The evidence that a fruit fly's immune response can adapt to - or retain memory of - an earlier infection contradicts the long-held dogma that immune memory cannot exist in invertebrates such as insects. Such memory of a specific pathogen, known as adaptation, is supposed to be a hallmark of the higher-level immune system response of humans and other vertebrates.
The Stanford work raises the possibility that humans could make use of this rudimentary immune response if their higher-level system is crippled. "It's a springboard to looking at the immune system in a whole new way," said David Schneider, PhD, assistant professor of microbiology and immunology and senior author of the study, which will be published in the Public Library of Science-Pathogens.
One of the two arms of the immune response in higher organisms is similar to that of flies. This arm is known as innate immunity, and it is thought to be a primitive first-line, nonspecific response to a pathogen "invader." The other arm found in higher organisms is adaptive immunity, which has a memory that retains an internal record of contact with an invader and - employing T and B cells - springs into action once it encounters the same invader again. This adaptive immunity explains why a vaccine provides protection.
"AIDS patients are like fruit flies in the sense that they don't have properly functioning T cells," said Schneider. "If there is anything we could do to make their remaining innate immunity better through adaptation, that would be really helpful."
Harnessing the potential power of adaptation in the innate immune system might also be a boon in the body's defense against bioterrorism or disease pandemics. "The B and T cells of the adaptive immune system take a long time to react," said Schneider. "But you might be able to speed things up if you could snort something up your nose that would make your innate immune system ready to fight."
While inviting novel ways of thinking about future vaccines and treating AIDS patients, the new finding immediately stirs up the field of insect immunology. Existing publications about the fruit fly's immune system explicitly state that it has no memory, and no ability to make specific long-term changes prompted by its exposure to pathogens. Because immune memory was defined as nonexistent, no one ever did the experiment to question whether the fly's immune system could adapt.
Then graduate student Linh Pham arrived in Schneider's lab. She was interested in pushing the boundaries of the assumptions of the innate immune system's limitations.
In the past decade or so, work done on fruit fly immunology has always been done on a fly infected only once - and that's not how things happen outside a lab, where a fly would be continually exposed to microbes. Pham thought to ask what happens when the flies encounter a microbe a second time.
Pham found a bacterium - Streptococcus pneumoniae - that infected the flies but didn't kill all of them. "I liken my work to the first vaccination experiments," said Pham, who is first author of the study. She essentially vaccinated over a million flies, typically doing 7,000 in a day, in numerous experiments. In a key experiment, she injected some flies with killed bacteria and others with just saline solution. She waited a week, then reinjected both groups with what should have been a lethal dose of live bacteria. Then she calculated the percentage of how many survived, compared with the flies that been injected only with saline.
"I didn't think the results would be so clean-cut," she said. Within two days, the second dose killed almost all of the flies that had initially received just saline solution. Those that had been vaccinated lived just as long - about one month - as a separate group that had not been infected.
To ensure it wasn't a fluke of the bacterium she chose, she tested other organisms. She identified a fungus that infects fruit flies in the wild, Beauveria bassiana, that elicited a similar protective effect. "It was really easy to show the adaptation part," she added. "Getting to the mechanism was the complicated part."
In the study, the researchers conclude that a much-studied receptor called Toll is involved, as are other processes. Pham is now teasing apart the finer aspects of how the fruit fly protects itself against S. pneumoniae.
Schneider and Pham said they hope their work encourages the search for a similar adaptive response in the innate immune systems of humans or other vertebrates. "One of the things that I thought was really cool about this work is that it might be a way to develop a vaccine that modulates the innate immune system," said Pham. "Of course, we are cautious about hoping for this."
Note: This story has been adapted from a news release issued by Stanford University Medical Center.
Source:Stanford University Medical Center Date:March 11, 2007
2007-03-09
Holographic Images look into Biology
Holographic Images Use Shimmer To Show Cellular Response To Anticancer Drug
Science Daily — The response of tumors to anticancer drugs has been observed in real-time 3-D images using technology developed at Purdue University. The new digital holographic imaging system uses a laser and a charged couple device, or CCD, the same microchip used in household digital cameras, to see inside tumor cells. The device also may have applications in drug development and medical imaging.
"This is the first time holography has been used to study the effects of a drug on living tissue," said David D. Nolte, the Purdue professor of physics who leads the team. "We have moved beyond achieving a 3-D image to using that image for a direct physiological measure of what the drug is doing inside cancer cells. This provides valuable information about the effects of various doses of the drug and the time it takes each dose to become significantly effective."
The laser is gentle and does not harm living tissue, Nolte said. The cancer cells used for the research were grown independently in a bioreactor in the laboratory.
Holography uses the full spectrum of information available from light, more than what the human eye can detect, to create a 3-D image called a hologram. By shining a laser on both the object and directly on the CCD chip of the digital camera, the system screens the pattern of light reflected back from the object and allows the camera to record very detailed information, including depth and motion on a scale of microns, or 0.0001 centimeter.
The scattered light waves reflected back from the object come together at the camera's detector and form what is called "laser speckle." To the eye, this speckle appears as a random pattern of blotches of bright and dark, but the pattern changes if there is motion within the object.
"All living matter is in constant motion, and the laser speckle from a living object is constantly changing with that motion," Nolte said. "This was the key to the diagnostic ability of the technique. The image appears to shimmer with the motion inside the cell. As the anticancer drug works, there is less motion inside the cell and the shimmer effect is reduced. This can be seen right on the screen."
The findings of this National Science Foundation funded research was detailed in an oral presentation on Tuesday (March 6) at the American Physical Society Meeting in Denver, Colo. The team was selected from more than 7,000 submissions as one of 25 to present results at a meeting press conference. John Turek, a professor of basic medical sciences at Purdue, and Kwan Jeong, a graduate assistant, collaborated with Nolte on this work.
The team detects the motion of organelles inside cancer cells. Organelles are tiny specialized structures that perform internal cell functions and are a common target of anticancer drugs because they play a key role in the uncontrolled cell division that makes cancer lethal.
Colchicine, the anticancer drug studied by the group, limits the ability of organelles to travel throughout the cell and perform their functions. The drug disrupts the growth of microtubules, the highways of the internal cellular structure, and leaves organelles stuck at dead ends unable to move.
This reduction in motion translates to less shimmer in the image on the screen and can be quantitatively analyzed by a computer program, Nolte said.
"Let's say there are 1,000 organelles reflecting light; the exact pattern of the laser speckle is sensitive to each organelle's location," he said. "If one moves even one-half micron, then the pattern changes. It is highly dynamic and sensitive to changes."
In addition to the technology's sensitivity to motion, the field of view is unique because of its "dynamic range," the difference between the largest and smallest scale accessed.
"We can look at a fairly large section of the object, about a 30-micron-thick section of a 700-micron-thick tumor," Nolte said. "At the same time, we can retrieve information within the micron scale.
"Biologists currently have to look at things on the cellular level through microscopes. With this technology, we now can detect things on the cellular level and the tissue scale at the same time. In this case, the whole is greater than the sum of its parts. Tissue is more than just an accumulation of cells. It is a communication network in 3-D that behaves differently than 2-D cell cultures."
In addition to realizing the diagnostic applications of the shimmer, the group has simplified and reduced the cost of the system.
In 2002 Nolte's group was the first to use holography to produce images inside of tissue. The original technique used special semiconductor holographic film developed by the team as opposed to a CCD chip.
"At the time, the only way to capture the image was on this very expensive, very difficult to make film," Nolte said. "But the CCD cameras kept getting better and better and reached the point where we could make the transition from holographic film to the CCD."
Light waves have peaks and valleys that offer information about depth undetected by the human eye. By shining a second laser directly on the CCD chip, bright and dark fringes occur corresponding to the relationship of these peaks and valleys. These fringes, or interference patterns, can be recorded directly onto the camera.
"This extra laser light wave, called the reference wave, acts like a yardstick," Nolte said. "It provides depth information and measurement. It gives us the original image layered with the fringes and the specific locations of these fringes tell us about the 3-D structure of the object."
The team combines this holography technique with "laser ranging," a method similar to radar that measures the time it takes for a laser pulse to travel to an object and be reflected back.
"The holography gives us the peaks and valleys and detailed depth information, while the laser ranging allows us to control how deep we are looking," he said.
The team plans to make measurements of the cytoskeleton, the support structure of cells, and to further examine what types of motion influence the shimmer effect.
"What we have seen is just the tip of the iceberg," Nolte said.
Note: This story has been adapted from a news release issued by Purdue University. Source:Purdue UniversityDate:March 9, 2007
Science Daily — The response of tumors to anticancer drugs has been observed in real-time 3-D images using technology developed at Purdue University. The new digital holographic imaging system uses a laser and a charged couple device, or CCD, the same microchip used in household digital cameras, to see inside tumor cells. The device also may have applications in drug development and medical imaging.
"This is the first time holography has been used to study the effects of a drug on living tissue," said David D. Nolte, the Purdue professor of physics who leads the team. "We have moved beyond achieving a 3-D image to using that image for a direct physiological measure of what the drug is doing inside cancer cells. This provides valuable information about the effects of various doses of the drug and the time it takes each dose to become significantly effective."
The laser is gentle and does not harm living tissue, Nolte said. The cancer cells used for the research were grown independently in a bioreactor in the laboratory.
Holography uses the full spectrum of information available from light, more than what the human eye can detect, to create a 3-D image called a hologram. By shining a laser on both the object and directly on the CCD chip of the digital camera, the system screens the pattern of light reflected back from the object and allows the camera to record very detailed information, including depth and motion on a scale of microns, or 0.0001 centimeter.
The scattered light waves reflected back from the object come together at the camera's detector and form what is called "laser speckle." To the eye, this speckle appears as a random pattern of blotches of bright and dark, but the pattern changes if there is motion within the object.
"All living matter is in constant motion, and the laser speckle from a living object is constantly changing with that motion," Nolte said. "This was the key to the diagnostic ability of the technique. The image appears to shimmer with the motion inside the cell. As the anticancer drug works, there is less motion inside the cell and the shimmer effect is reduced. This can be seen right on the screen."
The findings of this National Science Foundation funded research was detailed in an oral presentation on Tuesday (March 6) at the American Physical Society Meeting in Denver, Colo. The team was selected from more than 7,000 submissions as one of 25 to present results at a meeting press conference. John Turek, a professor of basic medical sciences at Purdue, and Kwan Jeong, a graduate assistant, collaborated with Nolte on this work.
The team detects the motion of organelles inside cancer cells. Organelles are tiny specialized structures that perform internal cell functions and are a common target of anticancer drugs because they play a key role in the uncontrolled cell division that makes cancer lethal.
Colchicine, the anticancer drug studied by the group, limits the ability of organelles to travel throughout the cell and perform their functions. The drug disrupts the growth of microtubules, the highways of the internal cellular structure, and leaves organelles stuck at dead ends unable to move.
This reduction in motion translates to less shimmer in the image on the screen and can be quantitatively analyzed by a computer program, Nolte said.
"Let's say there are 1,000 organelles reflecting light; the exact pattern of the laser speckle is sensitive to each organelle's location," he said. "If one moves even one-half micron, then the pattern changes. It is highly dynamic and sensitive to changes."
In addition to the technology's sensitivity to motion, the field of view is unique because of its "dynamic range," the difference between the largest and smallest scale accessed.
"We can look at a fairly large section of the object, about a 30-micron-thick section of a 700-micron-thick tumor," Nolte said. "At the same time, we can retrieve information within the micron scale.
"Biologists currently have to look at things on the cellular level through microscopes. With this technology, we now can detect things on the cellular level and the tissue scale at the same time. In this case, the whole is greater than the sum of its parts. Tissue is more than just an accumulation of cells. It is a communication network in 3-D that behaves differently than 2-D cell cultures."
In addition to realizing the diagnostic applications of the shimmer, the group has simplified and reduced the cost of the system.
In 2002 Nolte's group was the first to use holography to produce images inside of tissue. The original technique used special semiconductor holographic film developed by the team as opposed to a CCD chip.
"At the time, the only way to capture the image was on this very expensive, very difficult to make film," Nolte said. "But the CCD cameras kept getting better and better and reached the point where we could make the transition from holographic film to the CCD."
Light waves have peaks and valleys that offer information about depth undetected by the human eye. By shining a second laser directly on the CCD chip, bright and dark fringes occur corresponding to the relationship of these peaks and valleys. These fringes, or interference patterns, can be recorded directly onto the camera.
"This extra laser light wave, called the reference wave, acts like a yardstick," Nolte said. "It provides depth information and measurement. It gives us the original image layered with the fringes and the specific locations of these fringes tell us about the 3-D structure of the object."
The team combines this holography technique with "laser ranging," a method similar to radar that measures the time it takes for a laser pulse to travel to an object and be reflected back.
"The holography gives us the peaks and valleys and detailed depth information, while the laser ranging allows us to control how deep we are looking," he said.
The team plans to make measurements of the cytoskeleton, the support structure of cells, and to further examine what types of motion influence the shimmer effect.
"What we have seen is just the tip of the iceberg," Nolte said.
Note: This story has been adapted from a news release issued by Purdue University. Source:Purdue UniversityDate:March 9, 2007
2007-03-08
Seminar
This afternoon on group's regular seminar, I was triggered by our boss to explain a conception. I know of it fully, so stand up, walk straightforwardly to the white board to address, but failed. Everybody even seemed more confused after my expression. At last one of my senior classmate helped me. Then i asked myself, too nervous? No! Maybe I didn't open my mouth appropriately, express my brain right, maybe i should practise more to improve my oral skill. :)
In addition, we should bear in mind that IDEA and CREATIVITY is the origin and spirit of Science.
In addition, we should bear in mind that IDEA and CREATIVITY is the origin and spirit of Science.
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