From a humble point of view, as I was attending a bioinformatics and genomics workshop held in FOPCU, the lecturer was pointing to us, that up until now, no one has managed to come up with a method capable of converting a full-functioning protein back into the original nucleotide sequence on its corresponding gene. At that instance, the following thought occurred to me, as to why this would ever be needed?
For starters, we already have the protein in hand, its 3D structure is, for many, completely figured out and some even their orientation in space, their actions and functions. Then, as far as I understand, being the mould from which a protein is later assembled is the only function a gene, or one which is expressed anyways, has. Knowing that for instance, in gastrin hormone, the 4th amino acid is leucine, would it matter whether it was translated from the codon CUA and not UUG?
Now three thoughts impose themselves. I could only imagine that the presence of SNPs (which is basically a nucleotide that varies among individuals and thought to influence certain traits) within the nucleotide sequence of the gene is the reason behind the researchers’ attention. However, this ultimately means, that if a method were to exist, it would have to produce a different nucleotide sequence for proteins coming from different people. Simple logic.
Another probable explanation, that could come to mind, would be the existence of a difference in the structure of the leucine amino acid, held on tRNA molecules with varying anticodons, where each would have some “characteristic” features that distinguish it from the other tRNA. If that were the case, then it probably has managed to fly below the radar for quite some time, as no matter which reference I turn to, it is taken for granted that these amino acids are carbon copies. So being non-identical in any way, would cause the resulting protein to function in a slightly different manner, which could explain the diversity of their actions in varying individuals. Who knows?
Last, but not least, is the possibility of gaining fast insight into the genome of a previously undiscovered species of living organism, where one can quickly figure out all the expressed genes through this simple task of “reverse translation”. However sequences of the unexpressed genes would still have to adopt the old-fashioned way. No choice there!
Just wondering what the future has in store.
, gene sequence
, reverse translation
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Not too long ago, I read about a research done at the Kennedy Institute of Rheumatology Division, which has identified a new ligand for Toll-like receptor 4. This receptor was previously known for activating the immune system through the detection of threats as lipopolysaccharide or gram-negative bacteria. The new ligand, Tenascin-C, is an extracellular glycoprotein, whose elevated expression in cases of inflammation provoked scientists to study its role in the process.
The study noted that its presence was critical to maintain the ongoing inflammation seen in cases of rheumatoid arthritis. In reference to this study, the author stated “We have uncovered one way that the immune system may be triggered to attack the joints in patients with rheumatoid arthritis. We hope our new findings can be used to develop new therapies that interfere with tenascin-C activation of the immune system and that these will reduce the painful inflammation that is a hallmark of this condition”
I was able to contact Dr Kim Midwood and obtained this brief interview:
1. Do you have any speculations as to why Tenascin-C is overly expressed in certain individuals causing prolonged inflammation cases, whilst remaining within normal levels in others?
What regulates tissue levels of tenascin-C is not currently known and this is something that we are working on finding out.
2. From the different ligands of TLR4, why was Tenascin-C of particular interest in your research?
I have a long standing interest in how cell behavior is influenced by the extracellular environment, and in particular the role of extracellular matrix proteins in regulating cell phenotype during the response to tissue injury. For the last 10 years, I’ve been studying the role of tenascin-C – a protein specifically and transiently expressed upon tissue injury, but persistently expressed in chronic inflammatory diseases such as rheumatoid arthritis. This pattern of expression, plus the high homology of tenascin-C domains to other known pro-inflammatory matrix molecules or ‘DAMPs’ prompted us to investigate whether tenascin-C was an endogenous activator of the immune response and whether its persistent expression in RA contributed to disease pathogenesis.
3. What do you think the extent of similarity will be between the mice & human response to the Tenascin-C blockage?
I cannot predict how differently the mouse and human will behave.
4. Do you suspect a certain mechanism of the increase in inflammatory molecules caused by Tenascin-C?
We know that tenascin-C activates TLR4, activation of this receptor is well known to induced the expression of pro-inflammatory genes via activation of many intracellular signaling pathways.
5. How do you see the potential of such study for rheumatoid arthritis patients?
We plan to identify ways to inhibit the pro-inflammatory action of tenascin-C in the hope that this may be useful in reducing chronic inflammation in the joint.
Original research paper: Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease. Nature Medicine 15, 774 – 780 (2009). PMID: 19561617 (Vote for the abstract on Biowizard)
Image Credit: Davidson College Undergraduate Course
Tags: chronic inflammation
, intracellular signal
, Kim Midwood
, rheumatoid arthritis
, rheumatoid therapy
, Toll-like receptor
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This is not a prison break scheme. I was shocked to hear on BBC that researchers published a study, in the journal Genetic Vaccines and Therapy, about a new route for the delivery of specifically DNA virus vaccinations. Using the vibrating needle, normally used in tattoo parlors, they first experimented with mice & found a 16-fold increase in the humoral & cell-mediated antibody response elicited by these animals compared to the intramuscular injection. The needle implants small DNA fragments into the epidermis, which triggers a non-specific immune response believed to be the reason for the higher antibody levels found despite the lower dose of DNA used.
Flattering as it sounds, a lot of skeptics doubt that it would become a complete replacement of the conventional routes currently in use. It does not come without a cheap price either. Many tattoo lovers loathe the accompanying pain. Plus, potential users won’t be getting a tattoo in the process either because the needle won’t be loaded with ink.
Just truly amazed at whoever first comes up with such ideas and tries putting them to the test.
Image Credit: Enquirer
, Gene Therapy
, immune response
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Seriously, these days, no matter where I turn to, there is somebody contracting some form of bacterial infection that turns out to be pretty serious. At the beginning of the new year, a 20-year-old perfectly fit Brazilian model died of what appeared to be a Pseudomonas aeruginosa infection. As far as I know, polymyxins should work like a charm. Sadly, her life ended after enduring the amputation of her limbs and a nephroectomy procedure in an attempt to save her. And now again, rumor has it that Michael Jackson contracted a MRSA infection following a nose job.
Where did the antibiotics go? Is the bacterial resistance way ahead of us that we can’t even keep up? In a field study conducted amongst fellow neighbors & relatives, many did infact admit that they go rushing to their local pharmacies demanding a prescription of antibiotics for a mild flu or a fever of 38 degrees. Not that that is worse enough, they don’t comply to the pharmacist’s orders “if he did infact give an order” to administer it for the full course of the medication.
This should be a warning sign…an alarm triggering off right about now. Developed countries are already facing these problems, we shouldn’t be lingering around. Public awareness campaigns, maybe similar to those concerning the bird flu being aired these days, ought to be held. Our community is in desperate need of our expertise to guide, inform, and advise them about the consequences and potential threats at stake here.
“The window is closing and we’re coming to the end of the antibiotic era,” said J. Glenn Morris Jr., M.D., who heads the division of hospital epidemiology at the University of Maryland School of Medicine, College Park, MD. This was in 1999.
Can we really beat antibiotic resistance? or are bacteria getting the best of us?
Tags: bacterial resistance
, brazilian model
, michael jackson
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Yesterday, I was watching an episode of “The Doctors” where they were talking about a new study that completely amazed me…It was carried out at the Karolinska Institutet & the findings come in favor of men, mostly!! They found a link between a person’s genetic makeup & their relationship status. I have to admit that is pretty interesting.
The gene studied was AVPR1A, which actually has to do with one of the receptors for ADH, predisposes men to make unhealthy decisions, when it comes to relationships, once they have the allele 334. That is how it got its name, which it is pretty much now famous for as “The Commitment Gene”. Presence of two copies makes matter even worse…It is funny once you start thinking hmm..and how did they discover that!! The study was carried out on 550 sets of twins where they had to complete a survey evaluating their life in general & specifically when it comes to relationships..whether they are married, divorced, not ready to commit yet..
Luckily for the ladies, these genes can’t really dictate what a person does because that is all about his choices…but after all, it would be added on to the growing pile of excuses :). I wonder in the future if women would ask their future spouses to first undergo an examination and search for that gene…Who knows what the future might bring us!
, The Doctors
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To yet again prove Darwin’s theory, in a new study done in the University of Wisconsin, researchers have discovered that eight hearing-related genes have evolved over a time range of 40,000 years to cope with the ever-changing complex nature of verbal communication between human beings. Some of these changes are as recent as 2000 years ago.
As sound waves enter the ear, stereocilia “shown in orange” move. This movement is converted to electrical signals headed for the brain.
Seven of those genes are concerned with the production of proteins which make up the stereocilia & membranes that surround it. The 8th gene makes up structures which transmit sound waves to the inner ear.
Since communication requires both a talking tongue on one end & an ear capable of hearing on the other, the genetic changes concerning the ear must have favored a portion of the population to become better adapted to the “hearing process”. In any defense, they could have been able to detect on a more precise level, the emotional status of the person behind the spoken words, point out unconfidence in a specific speech, or even seperate out a conversation in the midst of a crowd.
This discovery certainly challenges the idea that languages have emerged from a single mutation which in somehow allowed the tongue to correctly twist, fold up & down, curve around within the buccal cavity & create the familiar sounds we know today.
This shows that not only human evolution has been going on since humans, or even neandertals for that fact, have existed but it continues all for the sake of a more prosperous life on our mother Earth.
Source & Image Credit: Science News
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The title stunned me as I was surfing the Yahoo News. At some evolutionary phase, birds really did have thumbs. So what happened to them? Researches at Yale University and the University of Wisconsin propose that it shifted its position after studies made on the gene expression in crocodiles, as published in PLoS ONE.
Going back now, birds have only three fingers, which until very recently where believed to be the 2nd, 3rd, and 4th respectively. The only problem this faced was that fingers in the early birds such as Archaeopteryx correspond to number 1, 2, and 3 “thumb, forefinger, and middle finger”. Fossil records clearly indicate that finger 4 and 5 “ring and pinky finger” were lost in the flying dinosaur ancestors of birds.
To end this debate, researchers began to focus on the expression of HoxD11 gene. In mice, digit 1 had no expression for this gene, which also held true for the 1st digit in birds, which suggests that in reality, it is actually a thumb. But to test this, it was compared to crocodiles, the closest living relatives to birds. The findings did in fact support what they suspected. The expression, as in mice, was absent only in finger one “the thumb”
So, birds at one time had thumbs. And the fact remains because they still do. It chose to develop at a different position in the body, that’s all.
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Researchers at Yale & the University of Chicago were faced with a surprising conclusion based on their scientific experimentation on mice. Unlike the common belief that microbes are in fact “bad” & possess a harmful threat to our health, some of these bacteria prove their innocence. Mice, that were exposed to common bacteria in the normal gut flora, were protected against the development of Type I diabetes. Previous research had shown that mice, exposed to killed Mycobacterium tuberculosis, were also protected. So, this means that mice that grow in their natural habitat are better off than the ones raised in the much improved sanitary conditions of the lab.
This comes to support the hypothesis many scientists have lately adopted. They tend to believe in a directly proportional realtionship between a person’s exposure to parasites, bacteria, worms, etc.. within the surrounding evironment and his immunity. The more, the better..that is within limits of course.
This actually makes perfect sense to me. It is really obvious when you see, for example, people living in third world countries with mosquitoes hovering around and considered normal. But when they travel abroad for a while and come back, they get different sorts of allergies & rashes from those previously “harmless” mosquitoes. What parasites and microbes do for you is not all bad. Unfortunately, I had to experience this dilemma.
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Recently, I have been able to get in touch with Professor Jan Roelof van der Meer after reading about his work in EurekAlert in the field of color-coded bacteria. Currently, he is an associate professor at the Department of Fundamental Microbiology, University of Lausanne.
In a review published in collaboration with Professor Robin Tecon, the researchers explained why the bacteria were specifically useful in the detection & tracing back the age of oil spills, chemicals and other pollutants leaking into seawater and the soil. Since the bacteria are easily manipulated, researchers were able to genetically produce MBS “Microbe-Based Sensors” which produce specific reporter proteins when in contact with a certain pollutant. Such reporter proteins can then be detected merely by observation or instrumentally.
Enclosed within the review, this figure illustrates the concept of a bacterial sensor-reporter cell where the benzene-ring-look-a-likes represent the pollutants.
And I leave you with the interview:
1. Is there hope that MBS won’t just play a role in detection, but in cleaning up as well?
Normally not. To enhance biodegradation rates in the environment, one usually tries to stimulate the bacteria which are already present at the site. There are no cases where genetically modified bacteria were applied to clean up contamination.
2. How can this method trace back the age of a spill?
Interestingly, we found that there seems to be a specific pattern of dissolution of different compounds from oil. A fresh spill will first ‘show’ linear alkanes and compounds like benzene, toluene, ethylbenzene. Only later will polycyclic aromatic hydrocarbons, like naphthalene, appear. We had not seen this before, because one typically cannot measure the first phase of an oil spill, since this is detected only after a while.
3. Which method do you prefer in the genetic engineering of these MBS?
Depends. For E. coli, we use very classical cloning techniques involving plasmids. For other bacteria, we have to use transposon delivery methods mostly.
4. Is the acquired trait of producing a reporter protein passed on to future generations of the bacteria?
Normally yes. If the reporter construct is integrated in the genome of the bacteria, it is relatively stably maintained even without selection pressure for the marker. When the construct is on a plasmid, like in E. coli, one has to constantly keep the ‘pressure’ for the marker on the plasmid, usually an antibiotic resistance marker.
5. This field, as you kindly mentioned, started 20 years ago; what hope lies for its progess in the future?
My major hope is that people (industries, labs) finally apply the methods in their analysis as alternatives for costly chemical analysis. Further progress has to come from miniaturization, multiple target detections and improved methods to preserve the bacterial cells.
, color coding
, genetic engineering
, oil spill
, reporter protein
, van der Meer
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In a study conducted by researchers in the University of Maryland School of Medicine, physical activity has proved to counteract FTO gene “fat, mass, and obesity-associated gene” in a group of European descendants who resided in the USA, known as Old Order Amish.
FTO gene has recently been linked to obesity & increased BMI “Body Mass Index” in numerous studies. Europeans usually have one or two copies of a variation of this gene. The research has enforced this prior assumption but brought, yet, another advantage since the study was done on 704 men & women of similar descent and thus similar genetic makeup, which what makes them ideal for genetic research. This helped researchers study the effect of physical activity on the expression of this gene.
In subjects, who were physically active throughout their daily routine, having multiple copies of the FTO gene didn’t seem to affect their BMI, despite the fact that in those, who were less active, a link between their BMI and FTO gene was obvious. This suggests that the choices one has to make in everyday life can deeply impact our body’s response to its own genes.
In order to compare the different variations in this gene, subjects were asked to wear accelerometers to measure their body movement on a 24-hour basis for seven days. They were then classified accordingly in order to conduct a comparative analysis. The genetic analysis revealed that 26 SNPs in the FTO gene were linked to BMI.
In the future, this may help tailor methods to prevent obesity in genetically susceptible individuals. So, after all we can’t blame it on our genes. Our decisions might in fact make up who we are & who we will become.
Source: Medical News today
Original research paper: Physical Activity and the Association of Common FTO Gene Variants With Body Mass Index and Obesity. PMID: 18779467 (Vote for the abstract on Biowizard)
, gene variant
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