Lyndsay LaMariana (11 AM Micro) read an interesting article from Science Daily, which describes some new research in the Stem Cell field, which apparently accomplishes something neat–one terminally differentiated cell from an adult is converted into a completely different type of cell. This research was recently published in the journal Nature Neuroscience. Here is Lyndsay’s summary:
After continuous years of research Harvard Stem Cell Institute, Boston Children’s Hospital, and Harvard’s Department of Stem Cell and Regenerative Biology have effectively found an answer to their unsolved quest. These biologists have figured out how to turn human and mouse skin cells into neurons in order to test pain. This pain can range from tenderness such as after getting a shot, to falling and cutting open ones leg, and lastly to burning oneself and screaming out in pain. This is a very important aspect in their research because it makes their research more valid. These neurons can react to many different stimuli’s and senses of pain which the human body can do as well, meaning that the tests they do on these stem cells react in the same way that we would.
This is very important research in the medical field because it can be used in order to test and create new medicine and treatments. For example, scientists now could use this method to test how human skin cells would react to cancer therapy radiation. Scientists could test how the skin cells would react and how strong they can make the radiation. Not only testing how strong the radiation that could be used, scientists can also test how it could affect someone. If a scientist used this method and the skin cells reacted poorly they could prevent this from happening in real life and prevent an actual human being from being harmed.
This research can also be used to test medicine that can be placed on cuts and wounds to facilitate healing. These ointments, lotions, and or liquids can be tested prior on the neurons of the skin cells. This again will allow for scientists to test if a patient will be highly in pain or uncomfortable from a certain type of medication.
The only downside of this research is that in the beginning it was tested on embryonic stem cells and didn’t work. The research only showed results when switched to adult skin cells. This brings upon the question that if medicine is tested on these stem cells to infer pain levels it might only be valuable for adults. However, this is a huge breakthrough and it will only grow bigger from here. This is only the beginning for research on how these skin cells can be used and how effective they are with receiving pain and reacting.
After 15 straight days of bonus point summaries from students, today brings a special treat as it falls to me to fill the space with content. This was a cool story, spotted via Microbe World from a news story on NPR, detailing work by researchers at Georgia State University and published in the journal Science this week. We are aware in BIO230 of the critical importance of the normal microbiota in helping us to resist pathogens and disease, however much of this benefit is due to the fact that we have developed a state of peaceful co-existence with them (meaning that they do not generally cause disease), and they are able to out-compete the bad guys. On the face of it, this is a rather boring picture, however the research outlined here shows that it is much more interesting and complicated than we might think.
The researchers were interested in developing treatments for a common gastrointestinal infection due to rotavirus. Rotavirus is a highly contagious agent that causes vomiting and severe diarrhea that can last for up to a week. According to the Centers for Disease Control, prior to 2006 rotavirus infections in United States accounted for around a half million doctors’ office visits, with a large number (greater than 50,000) of hospitalizations. Worldwide, there have been about a half million deaths due to rotavirus annually, mainly in children under the age of 5, and indeed young children everywhere are the most susceptible to infection and have the most severe signs and symptoms. Since the deployment of a vaccine in the last decade, hospitalizations due to rotavirus have begun to decrease, and epidemiologists believe that the unvaccinated are now beginning to see some of the benefits of the vaccine through herd immunity. Currently, there are no antiviral treatments for rotavirus infection, and of course antibiotics actually will prolong the disease course by eliminating the normal bacterial microbiota. The main treatments for rotavirus are to avoid dehydration caused by vomiting and diarrhea. Consequently, there is strong interest in identifying novel, oustide the box approaches for actually treating these types of infection when they occur.
The researchers introduced a bacterial antigen (flagellin), which is the major component of the prokaryotic flagella, under the skin into either healthy mice or mice infected with rotavirus, and observed that healthy mice did not subsequently develop rotavirus when infected (disease was prevented), and in the already infected mice the disease course was stopped (i.e. the mice were cured). The protection was independent of an adaptive immune response, meaning that no prior exposure to the virus was necessary in order to induce the response. The responses to the virus depended on two innate immune pattern recognizing proteins, Toll-like receptor TLR5 and NOD-like receptor NLRC4. The binding of flagellin to immune cells via TLR5 led to the production of a signalling molecule by those immune cells called Interleukin 22 (IL-22), which bound to intestinal epithelial cells and protected them from rotavirus infection. Production of a second Interleukin (IL-18) following stimulation by flagellin through NLRC4 actually eliminated rotavirus-infected cells.
The model being proposed is rather interesting. Bacteria in the gut do not normally cause disease, however components on their surface seem to have powerful immune stimulating capabilities in preventing infection by other, structurally unrelated pathogens. The researchers stress that this study demonstrates the protective nature of flagellin works in mice, which are not humans, and therefore a lot of work still needs to be done to show this holds true for us as well. Fortunately, the basic pattern recognition and signalling pathways are highly conserved between mammals, so there is no a priori reason to expect that these experiments will fail. As indicated in the introductory paragraph, we currently have a pretty good vaccine for rotavirus infection here in the US, which is starting to show real promise in reducing the numbers of rotavirus infection just since its introduction a few years ago. However, the vaccine seems to be poorly effective outside the US, possibly due to genetic variation between strains of the virus in different parts of the world. This approach, if it works in humans, will offer a way to circumvent this problem as it is takes advantage of a generalized innate immune response to a pathogen, as opposed to the specific adaptive immune response promoted by a vaccine. Since it is an innate immune response, there is also no reason to expect that it might not be effective against other virus pathogens that gain access via the gastrointestinal route..
BONUS: Given the discussion above, list in the comment thread ONE microorganism that might offer this protective effect, along with where you found that information. No repeats. You may have to do some research to find this. Offer runs through the end of Thanksgiving Break!!!!
Allie White (12:00 Micro) found two articles from Science Daily (here and here) describing a significant causal link between rates of smoking and the incidence of tuberculosis. Here is Allie’s summary:
Throughout the past couple of years there has been an increase in the amount of bacteria that are resistance to antibiotics. According to many scientists, one of these top microorganisms is Mycobacterium tuberculosis. Every year M. tuberculosis takes the lives of 1.5 million individuals. Once an individual contracts M. tuberculosis, it becomes quite hard to fight it off. Since scientists know this fact, one of the main ideas they are pushing is prevention by making changes in everyday life. According to Medical scientists at Trinity College Dublin and St. James Hospital , the main drive of the tuberculosis epidemic is smoking. This concept is not new, back into 2011 the British Medical Journal stated that smoking could lead to an excess of 40 million deaths by 2050. Because of this discovery that smoking contributes to tuberculosis, there is more of a push to anti-smoking campaigns across the globe.
One positive contribution finding this discovery is the fact that it has opened more doors to therapy and vaccines for the treatment of tuberculosis. So how does smoking cause tuberculosis? Well in order to answer this question individuals must look at tuberculosis facts and statistics. Tuberculosis spreads from person to person by inhaling droplets that come out the infected individual’s mouth. Nine million people, often immunosuppressed, get sick every year by inhaling droplets from people who are infected with tuberculosis. Over the years many outbreaks and multi-drug resistant tuberculosis cases have occurred in many countries across the entire world. Smoking increases this risk dramatically. Smoking increases the risk of recurrence, mortality, and persistent infectiousness of tuberculosis. It is important to note that the exact reason behind the connection between smoking and tuberculosis is still quite uncertain.
At St. James Hospital in Dublin, a group of researchers conducted a study that compared smokers, non-smokers, and ex-smokers. The results of the study supports that smoking and tuberculosis have a connection. The study revealed that the white blood cells located in the lungs of people who have smoked in their life, smokers and ex-smokers, had a weaker response to a tuberculosis infection. With white blood cells malfunctioning, they are unable to make the neurotransmitter that normally combats M. tuberculosis. An interesting result of this study shows that these malfunctioned white blood cells suppress the lungs immunity after infection, which is a perfect environment for M. tuberculosis to thrive and take over. Because of this study and the results it has found shows that tuberculosis and smoking are linked together. Since they are in fact linked together, the efforts on anti-smoking should be increased because the less people that smoke the less people get tuberculosis. According to Joseph Keane, the head of the study
Tuberculosis remains a huge global health problem, the affects millions worldwide . . . making smoking the biggest global driver of the TB epidemic.
Tuberculosis is no joke. Not only should the awareness of anti-smoking increase but it also is important to note that tuberculosis is very resistant to antibiotics. Therefore, research, time, and money must be put into both anti-smoking and new vaccine/antibiotic efforts.
Meghan Hegarty (12:00 Micro) found another article from Science Daily, which describes research from Georgia Tech with a new method for drug delivery. The eye is an immunologically privileged site of the body, which is the reason corneal transplants are actually rather easy to accomplish. However, this also creates other problems in that delivery of compounds through the bloodstream to the eye can be challenging. Here is Meghan’s summary, which describes an outside of the box approach to the problem:
Nearly everyone has heard of smoking marijuana to help treat glaucoma, but how effective can this method be? Researchers have discovered a more effective and reliable method, one that involves the eye to be punctured by small needles. Microneedles that are no larger than 700 microns, can deliver drugs to specific areas of the eye rather than the whole eye. By this method, researchers believe the effectiveness of the treatment can be increased, as well as limit side effects and reduce the amount of drug needed to treat both glaucoma and corneal neovascularization.
Glaucoma is the second leading cause of blindness in the world and affects more than 2.2 million people in the United States alone. The microneedle injection treatment method could replace daily administration of eye drops and only be needed every three to six months. The second disease, corneal neovascularization, results in the growth of unnecessary blood vessels that impair vision. For this disease, researchers have created a treatment that would inject a dry drug compound to stop the vessel growth via a solid microneedle. The use of needles to treat eye conditions allows doctors to deliver the drug within the eye to specific areas, rather than the whole eye. Mark Prausnitz of the School of Chemical and Biomolecular Engineering at the Georgia Institute of Technology states that they are developing “different microneedle-based systems that can put the drug precisely into the part of the eye where it’s needed.” To further improve this, researchers want to create a drug that is has a controlled-release formulation that would allow one application to treat the condition for months.
The research is being supported by the National Eye Institute of the National Institutes of Health and is currently being tested on animals. The new treatments have become necessary since only about fifty-six percent of glaucoma patients follow the appropriate treatment protocol to their eye disease. Glaucoma is currently being treated with eye drops that need to be applied daily, a nuisance to many. The microneedle would inject drugs into space between two layers of the eye near the ciliary body. The drug would stay near the injection site and would reduce intraocular pressure through the injection. Because the injection targets a specific site, researchers are able to reduce pressure by using only one percent of the amount of drug that is required to produce a similar reduction with eye drops.
The ultimate goal for the researchers would be for patients suffering with glaucoma is for them to only need to visit a doctor to get the injection, and not need another injection for the next six months. Getting rid of the eye drop treatment method would potentially have better control of the symptoms and treatment. To treat corneal neovascularization, the needle would need to be help in place in the eye for roughly one minute until the drug dissolved into the cornea of the eye. In animal testing, the drug stopped the growth of unwanted blood vessels for about two weeks after one application.
Currently, eye injections are being completed with hypodermic needles that are much larger than the microneedles to administer a drug into the center of the eye. While patients tolerate this method, the microneedle treatment would not cause significant side effects and are tailored specifically to penetrate the eye only as far as needed to deliver the drug. For example, the needle required for glaucoma treatments would only need to be about half a millimeter long. Before this new treatment method can become available to people, more animal testing needs to be completed. If all goes well in the animal trials, people would have a much more effective and convenient method to battle their eye conditions.
Gracen Schilling (12:00 Micro) found another article in Science Daily that interested her, describing the work of scientists at Stony Brook University. This research describes a causal link between major depressive disorder (MDD) and the presence of an infectious agent. Longtime BIO230 readers will of course recall the link I found a few semesters back which seems to show a link between MDD and a generalized immune response that might not have as important of a role in our defenses today; that is MDD outbreaks might be due to an evolutionary relic of our ability to fight off infection. And if you are depressed, eat some yogurt to make yourself feel better. Anyway, here is Gracen’s summary:
An article I found on Science Daily proposed a theory that has brought up a brand new way of thinking; could depression be a form of an infectious disease? According to Turhan Canli, a professor of Psychology and Radiology and author in Biology of Mood & Anxiety Disorders, major depressive disorder (MDD) causation should be completely reevaluated to an infectious disease being the etiological agent. Dr. Canli says that MDD is likely to be from a parasitic, bacterial, or viral infection based on the pathways of each of these microorganisms. He argues that this is likely because first of all, people who have MDD have behaviors of illness like energy loss, which is very common in depression patients. Dr. Canli’s studies have also shown that the inflammatory biomarkers of MDD suggest that depression is more likely an illness related problem. Other studies have also shown that microorganisms like parasites, bacteria, and viruses can infect human hosts resulting in a shift in emotional behavior. Since the shift of emotional behaviors is a huge factor of MDD, this is a plausible theory. Dr. Canli’s third argument is that the human body is obviously an ecosystem for microorganisms and the role of viruses in the human genomes. The arguments of the human body as an ecosystem for these microbes makes sense since us humans do have multiple microorganisms growing inside of us. If these particular microorganisms flourish in the environment our body encases than their reproduction would definitely increase; likely causing an increase in symptoms and issues like MDD’s. The role of the human genome is likely related in some way to the retroviruses found in us, which would be a plausible reason for the genetic passing of MDD.
MDD being caused by an infectious disease is also backed up by the role of medicine. Dr. Canli suggests that since recurrence is very common and the medical treatments have remained consistent over time; research done on MDD obviously needs to broaden. Since no simple aspects of MDD have been defined clearly, new research to improve treatment is very important. With the high prevalence of MDD in the population today, it is obvious that even if this is not an infectious disease, the treatment methods still need to be reevaluated due to their faults. Dr. Canli ends by suggesting that a great research step would be to conduct a large-scale study of depression in patients with controls and protocols for infectious diseases. This would help conclude if MDD’s nature shows a correlation between depression and infectious disease possibly caused by any of the three microorganisms in which he found evidential reasoning towards having a role in depression.
Meghan Hegarty (12:00 Micro) found an article in Science Daily, which describes research examining how differentiated cells might be reprogrammed to better help with the healing process. For the curious among us, the compounds described by Meghan down below which promote this reprogramming are molecules that mimic viral RNA genomes, and as a result can stimulate certain host cell signalling pathways that we will learn about in the next chapter in Bauman. Here is Meghan’s summary:
Recent discoveries have shown that by transforming human scar cells into blood vessel cells, the repair of damaged tissue can be completed. Cardiovascular scientists of Houston Methodist and several others from Stanford University and Cincinnati Children’s Hospital learned new information that can remove scars. By coaxing fibroblasts into becoming endothelium, a different type of adult cell forms, creating the lining for blood vessels.
According to John Cooke of the Houston Methodist Research Institute Department of Cardiovascular Sciences, this is the first time a transformation of cell type has been completed along with the use of molecules and proteins. By turning fibroblasts into new cells, the possibility of molecule therapy to improve the healing process of cardiovascular damage or other scars may now be an option. Another way to generate endothelial cells is to use infectious virus particles to manipulate genes in DNA. To do this, DNA must encode proteins to alter gene patterns in a way that behave like endothelial cells. However, John Cooke states the using viruses to transfer genes into cells can cause multiple problems. This approach is more complicated and the possibility of damage to the patient’s chromosomes is higher. Manipulating fibroblasts is easier to complete and overall safer for clinical therapies.
To complete the method that Cooke suggests, fibroblasts have to be exposed to polyinosinic: polycytidylic acid that binds to toll-like receptor 3 which tricks the cells into reacting, like they are being attacked by a virus. This can be described as fibroblasts responding to a fake viral attack, which is an important step in the transformation of fibroblasts to new cells. After treating fibroblasts with polyinosinic: polycytidylic acid, other factors come in to play to compel less differentiated cells into becoming endothelial cells.
Rates of fibroblast transformation are somewhat low now, at only two percent of the fibroblasts transforming into endothelial cells, but the transformation rates are expected to get as high as fifteen percent. Cooke explains that this rate will provide the perfect amount of transformed cells, as not all fibroblasts need to be transformed. Fibroblasts perform important functions such as making proteins that hold tissue together. The approach to transforming fibroblasts will transform some of the scar cells into blood vessel cells that will allow blood flow to heal an injury.
In another part of the study completed, scientists introduced transformed human cells into immune-deficient mice that had a poor blood flow to their back legs. By incorporating human blood vessel cells into the mice, there was an increase in the number of vessels in the mouse limb which overall improved their circulation. The cells self assemble to form new blood vessels by joining with existing vessels in the mice. By figuring out how to manipulate adult cells of one type into a different type of cell, further development of regenerative medicine can be completed. Considering humans are usually unable to regenerate heavily damaged tissue, this process can become very important.
If the scientists can understand the underlying pathways and how to manipulate them to benefit people, new information to reawaken important mechanisms for regeneration can be discovered. More animal studies are needed before the scientists can begin clinical trials, such as seeing if they can heal an animal from an injury by this new method. Before testing this on humans, the scientists want to know if the therapy enhances the healing process by increasing blood flow to tissues that may have been damaged by a loss of blood.