Archive for the “Advances” Category
What could those three possibly have in common? Believe it or not, they all play the role of a lead action figure in kids video games. Hearing the latest edition of the german biotechnology news broadcast, I was surprised to learn that researchers at the Riedel-Kruse Lab in Stanford University have developed, what-they-call, Biotic Video Games, where the paramecium are controlled and maneuvered about via a joystick and managed to publish their findings in a research paper!
The device is basically composed of a fluid compartment, where the paramecium move around and roam about freely. I am sure you are wondering, exactly how
BIG (small) IS a paramecium. Well, it is so small, making it actually difficult to observe by the naked eye. But no worries! They can be seen quite clearly on your screen, while you’re playing, thanks to the provided microscope camera, which is connected to electrodes and supplies you with a live feed, being superimposed on the flash game board onto your screen. The joystick is capable of creating a weak electric field, which influences the direction of their movement, as you wish.
Eight different games have been developed and given quite funny names, as Ciliaball, Pac-man and Pond Pong. For instance, in one game version, the player needs to move about the paramecium to score a soccer goal. To help you easier imagine this, take a look at this 3-part video.
As Riedel-Kruse put it, these games serve two ultimate goals: First, to awaken the scientific interest in those young kids and teenagers, hopefully motivating them to someday pursue a career, heading off in that direction. And after all, scientists can collect and analyze information about those tiny organisms, whilst playing with them.
So please do take a break and enjoy some time away with your paramecium
Image Source: Stanford University Schools of Medicine and Engineering
Riedel-Kruse IH, Chung AM, Dura B, Hamilton AL, & Lee BC (2011). Design, engineering and utility of biotic games. Lab on a chip, 11 (1), 14-22 PMID: 21085736
Tags: biotech game
, biotic game
, electric field
, flash game
, super mario
, super sonic
, video game
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Though risky, transplants are crucial treatment interventions for many patients.They can save lives of cancer patients, others with severely ill organs and recently there are trials to make them a mainstream treatment for autoimmune disease patients ( i’ve just read an article about that topic and i’d really love to write about it soon too).
But the major problem with transplants, other than the agonizing wait for the right donor on endless lists for sometimes many years, is that when things go wrong with transplants, the patient’s life becomes at mortal risk. Almost 40% of transplant patients will show rejection episodes within the first year after the operation. The detection of these immunological reactions are usually so late, and the only solution will be to flush the patient’s system with huge doses of immunosuppressive drugs that are toxic themselves and can have debilitating effects on cancer patients for instance. Also, to be able to detect rejection reactions, the doctors should take biopsies of the new organ, a process that can cause damage to the organ itself, let alone the stress and the already fragile patient condition. Transplant patients have to undergo exploratory biopsies monthly for one year after the operation!!!!!
Will these risky, life-saving procedures be safer in the future?
Early detection of these reactions was an interesting topic and a field of research for the cardiologist Hannah Valantine of Stanford University School of Medicine in Palo Alto, California. In 2009, she devised a new test that detects the immunological changes in a transplant patient in an episode of rejection. The test, called AlloMap, became the first of its kind to be approved by the FDA for use in the detection of heart transplant rejections. Yet, it failed to detect the rejections early in about half the patients.This, of course, didn’t satisfy Valantine.
Along with biophysicist Stephen Quake of Stanford, they came out with a much more sensitive test. The idea was that DNA from the new organ constitutes around 1% of the free DNA in blood of transplant patients. This DNA is foreign from the DNA of the patient and using her test, it can be very sensitively detected, despite the fact that it is circulating in minute amounts. To validate their test, they used it on stored plasma samples from transplant patients that later showed rejection signs. It was found that the amounts of the rejected organ’s DNA in such episodes are elevated soon after the surgery and constitutes around 3% of the free DNA in plasma, and of course, will be much elevated later, in the peak of the episode. They reported the results in The Proceedings of National Academy of Sciences.
The good thing about this test, besides its high sensitivity, is that it is much less invasive than a biopsy, and the biopsy will not be needed except for confirmation, in case the test is positive and the DNA % is higher than normal. Also, early detection will allow doctors to use much smaller doses of immunosuppressives to control the case and therefore, less side effects will be experienced. Valantine is a cardiologist, but believes the test can be used with other types of transplanted organs, other than hearts.
, organ rejection
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Infections in the teeth implants are dreaded, running a high risk of potentially affecting the jaw bones. It is actually not that uncommon. The overall number of performed teeth implantations in the US and Europe has doubled over the last decade, yet studies show that 10 percent of the implants are associated with problems, usually in the first year directly after the operation. To prevent any further deterioration, the implants sometimes have to be removed.
New methods are now being developed by researchers in the University of Zurich to keep inflammation-causing bacteria at bay. In their PLoS ONE article, they present their materials and methods, which have successfully eliminated 99% of the microbes after a 15-minute electrical treatment.
Conventional treatment methods of this sort of inflammation depend on the utilization of topical antibiotics, which is surely a burden for the patient. The aim of the study was to develop a non-invasive approach to efficiently fight off the bacteria, or, as the researchers phrase it in their paper, to develop “an in-situ decontamination of the dental implants”.
The whole idea is based on the process of water treatment, where sterile water is produced through electrolysis. In order to simulate the conditions in the jaw, an Escherichia coli bacterial film was coated onto the titanium implants, which were impregnated in a gelatinous preparation. In the experimental design, one implant functioned as the cathode and the other as the anode. The implants were subjected to a 15-minute-long electrical treatment, of an intensity ranging between 0 and 10 Milliampere. This artificially generated electrical field caused the hydroxyl ions of the water molecules to migrate to the cathode, and thus raising the pH. A color change of the indicators, used in the gelatin, prove that an alkaline environment predominates at the cathode. On the other hand, the pH value drops at the anode, forming an acidic milieu.
The numerous experimental models with various electrical intensities show that in cases, where an acidic ambience was produced around the implants, 99% of the bacteria died off after a 15-minute treatment. Therefore, the patient implants in the future will take up the role of the anode. A clip at the lip will be used as a cathode.
What at first glance might seem as a torture mechanism is in reality completely harmless. The minute amount of Milliampere, which is sufficient to conquer the bacteria, is hardly even perceived by the patient and would tops cause a mild muscle twitching.
, escherichia coli
, PLoS ONE
, teeth implant
, Universität Zurich
, zurich university
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If you have ever been one of the unlucky ones waiting for a cancer diagnosis biopsy, or having a friend or a relative undergoing the process, then you must know how the wait is nerve wrecking. The standard procedure is using a biopsy needle to extract some cells of the tissue suspected for cancer, and then waiting for about a week, until the results come out. To make matters worse, results can sometimes be inconclusive or 100% correct.
Simple smartphone applications might be able to rapidly diagnose cancer in the future
Fortunately, a group of scientists at Massachusetts General Hospital (MGH) in Boston, were able to develop a new technology, that is much more rapid and almost 100% accurate in the diagnosis process. They developed a small NMR device (detects compounds by the mode of oscillation of their nuclei in a magnetic field) the size of about a coffee cup, and they were also able to synthesize magnetic Nanoparticles, which stick to certain tumor specific proteins. So now all I have to do, is head to the clinic, have the needle biopsy performed and the cells taken. Then they are mixed with the magnetic Nanoparticles and the results are taken from the small NMR device and read using a simple smartphone application.
This technique was used in the first trial on 50 patients, taking less than an hour to diagnose each. Also, as the device can detect 9 tumor associated proteins, combining the results for 4 of these gave accurate results in 48 out of the 50 patients. In another trial, the accuracy was 100% in the 20 patients tested. The conventional tests’ average accuracy is 74-84 %.
This new technology will also cut down on the cost of repeat biopsies, which can be very expensive, and scientists hope it will have many other applications as well, like patient cancer follow-up, through quantitative analysis of the tumor associated proteins. Maybe the biopsy will not be needed in the future and a simple blood test will also do….
, cancer diagnosis
, magnetic nanoparticles
, smart phones
, tumor associated proteins
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A simple online search for anti-microbial clothing and you are bound to come across an assortment of brand names, even Adidas, promoting their products, mostly sportswear. But are they really safe? To answer this question, researchers at the Hohenstein Institute tested the safety of such anti-bacterial textiles. The result: Even in cases of volunteers, who wore those clothing articles for an extended period of time, their skin flora was not affected.
Over the last years, anti-microbial textiles have gained popularity. It started off in the medical sector in an approach to cut down on cross-infection between patients and to ensure the safety of the hospital staff. Recently, the industry has managed to find potential customers, those who are interested in sport and outdoor activities, looking for ways to control bad odours. The majority of these products, found on the market, are manufactured using anti-bacterial silver strands, which help in “eliminating 99.9% of odour-causing bacteria” as one ad claims. Furthermore, one firm releases products to be used in cases of neurodermatitis. On their homepage, it is stated that, “our silver textiles provide a realistic alleviation of this agonizing skin disease” and are backed up by statements of health experts.
Despite the previous positive experiences concerning the implementation of silver, like in the purification of water, anti-bacterial clothing have raised a controversial discussion in the media. This encouraged researchers to run a 6-week-long experiment, in which 60 healthy volunteers participated. For the study, special T-shirts were manufactured, which conveyed antimicrobial activity on one side, yet a non-antibacterial placebo effect on the other. For confirmation that this model actually did exert an antibacterial effect, the T-shirts were tested in the laboratory using Staphylococcus aureus und Klebsiella pneumonia. The volunteers were instructed to wear the T-shirts for at least 8 hours each day during the course of 4 weeks. The researchers analyzed on a weekly basis several parameters concerning the skin flora. In all the participating volunteers, the skin flora, both before and after, were within the normal range. There were no threats of a skin pathogen at any time. Therefore, these clothes have been characterized as being harmless and it seems like, their market will continue to expand as more people appreciate the benefits of leading an active life style.
, bad odour
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This post on Microbe World entitled: “Software for Programming Microbes” did attract my attention, and I followed its source in the MIT Technology Review: An amazing article presenting a fascinating newly emerging technology of programming bacteria to do whatever we want them to do, produce drugs more efficiently, clean up oil spills, anything… useful! But the methodology was quite beyond my imagination.
I was extremely lucky to be able to interview Dr. Christopher Voigt, Associate Professor at the University of California, San Francisco, who is the project leader. Dr. Voigt has published over 34 articles indexed in Pubmed and you can find more about his projects on his lab website.
Now I will leave you with the interview! I thank Radwa for reviewing it.
Dr. Christopher Voigt
1. May you please simplify the term “genetic circuit” to the micro-readers? What drove you to use software to genetically modify bacteria?
A genetic circuit functions like an electronic circuit, but uses biochemical interactions to do the computation. I am a computer programmer at heart and find living cells to be the ultimate challenge.
2. We used to hear a lot about the use of genetically modified bacteria in cleaning up toxicants or oil spills, producing drugs and biofuel. How is “programming bacteria” different from the “regular” definition of genetic engineering, which might be based on inserting a gene, a regulatory gene, or an operon that encodes for a certain needed functionality?
Genetic programming controls the timing and conditions under which those processes occur. It doesn’t refer to the pathways by which molecules are made or degraded.
3. In MIT Technology Review, you mentioned that like for a computer, programming bacteria is about writing a program to be encoded on a piece of DNA to implement a function. How can bacterial cells understand the code? How can the software make them sense the outer media?
The DNA contains codes for when molecules like proteins and mRNA should start and stop being produced and under what conditions. A protein can change its state when it senses a condition and bind to DNA to cause genes to be turned on or off. This acts like a sensor.
4. Honestly, I can’t imagine writing a piece of code to link bacterium to one another, because node->pRight!=NULL ? I just can’t imagine it. Is there any risk of overloading natural functions by accident?
5. How can programing bacteria make use of quorum sensing?
Quorum signaling enables cells to be programmed to communicate with each other.
6. How can drug discovery and production benefit from programmable bacteria in the near future?
It makes it easier to access and control those pathways.
Tags: Christopher Voigt
, genetic circuit
, programmable bacteria
, quorum sensing
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For a long time, mental retardation was believed to be incurable, as it is usually caused by gene mutations that disrupt brain development right from the beginning and even before birth. But thanks to a lot of hard-working scientists, there are trials now to improve the quality of life of such patients, along with their caregivers. The work has been focused on a condition known as “Fragile X syndrome”. In this disease, a mutation takes place in a gene called FMR1 , which is responsible for the production of proteins, that regulate neural development, usually leading to mental retardation according to the extent of such mutations.
Fragile X syndrome's common physical symptoms : elongated face, large ears, etc
Another important contributor to the condition is the metabotropic glutamate receptor-5, abbreviated to mGluR5. It is responsible for controlling the process of protein synthesis at the neuronal synapses, becoming hyperactive in case of fragile X. Being an interesting therapeutic target, a major pharmaceutical company developed AFQ056, an mGluR5-receptor blocker, in the hope that it’ll restore normal transcription levels. The results of the initial double blind clinical trials, conducted on 30 patients, were evaluated through the notes taken by the caregivers about the behavioral improvements of the patient. This included less repetitive behavior, less hyperactivity, less tantrums and having better chances of establishing communication with the patients.
What seemed like a puzzle is that some caregivers reported no change at all after the patients took the drug. So after data analysis, the researchers found that the only patients affected by the treatment were the ones (7 patients out of 30) having a certain genetic marker: complete methylation of the FMR1 gene regulator sequence, and therefore, complete lack of FMR1 transcription. Another disappointment was that the drug didn’t improve cognition or memory, but this, they say, might be attributed to the short duration of the trial, lasting for only 4 weeks.
The next step is to repeat the trial, but this time on 160 selected patients, after testing them for the marker and the experiment will last for 3 months, hoping to obtain better results that are more significant to the patients of this illness.
Sources: Wikipedia and Science News
, fragile X syndrome
, mental retardation
, metabotropic Glutamate receptor 5 blockers
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Which hair colour a person possesses depends mainly on the proportional amount of two melanin pigments, mainly the black-brown pigment, known as eumelanin, and the blond-red pigment, known as pheomelanin. The assortment of hair colours present is a consequence of the numerous combination proportions of each pigment.
For quite some time now (since 1997), the gene responsible for the classic red-hair phenotype has been discovered. At that time, the research team was concerned with the MC1R gene on chromosome 16. Its role was the production of MC1R receptor, which assists in the conversion of pheomelanin to eumelanin. Individuals with two copies of the recessive gene, causing a mutation in the MC1R, are most likely to turn out red-headed due to the build-up of pheomelanin. However, since the other hair colours are controlled by a variety of genes, it was, until recently, a tough task to predict a person’s hair colour from strands of his/her DNA.
Now, researchers at the Erasmus University Rotterdam have released an article identifying 13 DNA markers, located on 11 genes, which can guide us to the prediction, with a fairly high accuracy, of an individual’s hair colour. “For our study, the authors utilized the DNA and the accompanying information regarding hair colour from hundreds of Europeans and analysed various genes, that were previously known to be involved with this trait”, pointed out Professor Manfred Kayser, who lead this study. The accuracy percentage is as high as 90% when it comes to black and red hair, but dropping down to 80% or more with blond or brown hair.
The further potential implications of the study will soon be applied to forensic investigations. Along with their previously published work regarding eye colour and height from the DNA, these researchers aim at forming a descriptive profile of previously unidentified individuals, whether victims or offenders.
, forensic medicine
, hair colour
, red hair
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Forget about the old Petri dishes and culture media! A brilliant new method for the growing of microorganisms in order to study their behavior, especially in a large community, again tracking the phenomenon of quorum sensing , has been developed and put to use.
The new invention, by Connell et al., resembles a trapping sack for microorganisms, made of bovine serum albumin covalently cross-linked by laser lithography to form a three dimensional structure. These harboring chambers are very small, with a 2 to 6 picoliter capacity, and are permeable, and thus allowing an infinite influx of nutrients and other essential small molecules for the bacteria growing inside.
Scientists have already compared the growth rates of Pseudomonas cells in “the trap sacks” to those in conventional culture media and mouse lungs and the results were promising! The new technique allows them to study patterns of antibiotic resistance, infection and biofilm formation more clearly and in earlier phases of bacterial growth…
Source: Science magazine, Vol. 330 issue 6004.
Image source: Microbiology Bytes
Tags: antibiotic resistance
, culture media
, microbial trapping
, pseudomonas biofilms
, quorum sensing
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The pursuit of renewable sources of energy just hit a crucial breakthrough. Since the stores of fossil fuel are diminishing as we speak, researchers are trying to exploit the machinery of microorganisms for the production of diverse chemical compounds, which can be consumed by themselves or later channeled into some form of combustible fuel. One major group of those compounds are alkanes, those saturated organic compounds abundantly found in gasolline.
The study started off when ten out of the eleven strains of Cyanobacteria, that were photoautotrophically cultured, produced forms of alkanes, mostly those with 15 & 17 carbons atoms “termed penatdecane and heptadecane respectively”. Logically, that indicates that the ‘alkane-producing gene’ is shared in all ten of them, yet absent in that unlucky 11th strain. So the search was launched.
Trying to pinpoint the gene responsible for the production of alkanes through using a method referred to as subtractive genome analysis, the study authors compared ten genomes of the alkane-producing strains to figure out which genes they have in common. Next, any of those shared genes was immediately eliminated if it had additionally showed up in the genome of the NON-alkane producing strain. Eventually, the researchers were left with 17 genes found in common and the function of 10 of them had already been previously assigned. Through careful scrutiny of the families to which proteins of those remaining 7 genes probably belong to, two of them particularly stood out, being likely participants in the pathway of the alkane synthesis.
And as always, there is no better way to test the hypothesis than to consult a microbiologist’s favorite lab microbe. To our pleasant surprise, extracts from the colonies of Escherichia coli engineered to express both genes did in fact contain alkanes. So, although we are still not fully aboard the track heading the way towards large scale production of alkanes using such microbes, this is definitely a gigantic leap in the right direction!
, escherichia coli
, subtractive genome analysis
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