AP Biology class blog for discussing current research in Biology

Tag: #mutations

CRAZY NEW COVID-19 Mutation Makes Virus Weaker Against Antibodies

As revealed in a fascinating article that details a study conducted by the University of North Carolina at Chapel Hill, a mutated form of the virus has been discovered to be much more susceptible to antibodies produced by antibody drugs. This means that it is more easily disabled by antibodies produced by drugs such as the new vaccine. However, this may not all be good news as this new strain, called D614G, is also much more transmissible. D614G originated in Europe and has quickly become the most prevalent form of the virus. According to professor of epidemiology at UNC Ralph Baric, “The virus outcompetes and outgrows the ancestral strain by about 10-fold and replicates extremely efficiently in primary nasal epithelial cells, which are a potentially important site for person-to-person transmission.” These nasal epithelial cells act as a physical barrier against any pathogens attempting to enter the body and play a significant part in the control of the innate and acquired immune response. As we learned in biology, one method of innate immune response that our bodies have is mucous that traps pathogens. The nasal epithelial cells contain cilia that act to push the mucous and the pathogen contained inside out of the body. This means that if this new virus reproduces exceptionally well within the nasal epithelial cells, then it is extremely transmissible through any expulsion of mucous by either sneezing or coughing. It is also far more capable of bypassing the barrier of the mucous and entering the body. These epithelial cells also help the innate immune system by producing various cytokines. If a virus manages to make it past the barrier defenses, the epithelial cells will secrete cytokines. These cytokines will attract a type of cell called a neutrophil that digests pathogens. This means that these nasal epithelial cells are vital to the innate immune response and having a virus strain reproduce so effectively inside of them is extremely worrying.

The researchers believe that D614G is so effective at reproducing because it increases the virus’ ability to enter cells. The D614G mutation opens a flap on the tip of one of the spikes on the side of the virus which allows it to infect cells more effectively. However, this mutation also creates a weakness in the virus. When the flap is open, it becomes much easier for antibodies to bind to the spike proteins, preventing the virus from attacking additional cells.

Two researchers from the University of Wisconsin contributed to this study by experimenting with hamsters. To test the airborne aspect of this mutation, the hamsters were placed into different cages and groups so they could not touch and inoculated with either the original strain or D614G. By day two, in the group exposed to the mutation, six out of the eight hamsters were infected with D614G. In the group of hamsters exposed to the original virus, no additional hamsters were infected by day 2. This shows that this D614G is extremely effective at being transmitted airborne. However, the mutation had the same symptoms and effects as the original virus meaning it is not more severe. The researchers have also noted that these results may not be the same in human studies. I think that this study is equal parts of good and bad news. I am glad that the most prevalent form of the virus is much easier to deal with, but it is quite terrifying that it could mutate to be so much more contagious. How do you feel about this new development? Let me know in the comments. 

Some People Can’t Smell Stinky Fish?!

A New York Times article has just reported a new “mutant superpower.” In Iceland, a brand new genetic trait was discovered, in which 2% of the population can’t smell the stinky odor of fish. 

A study of 11,326 Icelanders was conducted, in which each participant was given six “Sniffin’ Sticks (pens imbued with synthetic odors)” of cinnamon, peppermint, banana, licorice, lemon, and fish. The participants were then asked to identify the odors based on how strong each smell was and how good each Sniffin’ Stick smelled. Across the majority, the fish was rated the lowest in pleasantness. However, a small group of people actually enjoyed the scent, noting that it smelled like caramel or even a rose. 

This small group of participants was discovered to have a genetic mutation that enables the TAAR5 gene to form. TAAR5 (Trace Amine Associated Receptor 5) aids in making proteins that recognize trimethylamine (TMA), a chemical found in rotten and fermented fish, and some bodily fluids, including sweat and urine.  TAAR5 is also a G Protein, meaning that it binds guanine nucleotides. And, like other coding proteins, TAAR5 is a quaternary structured protein that has three subunits. Because this protein is incapable of binding guanine nucleotides, it means that there will be at least one “broken” copy of the gene that codes for the inability to smell fish. 

To simplify: TAAR5 recognizes the chemical of smell in fish (TMA), however, with the mutation that prevents the TAAR5 from forming, the smell of fish (TMA) is unrecognizable.

Interestingly, research has shown that this mutation may be a reaction to the customs of Iceland and a possible next step in the evolution of the region. In Iceland, fish takes a prominent place on most menus including dishes like “rotten shark.” These cultural and possibly smelly dishes may explain why this mutation is much more prominent in Iceland compared to Sweden, Southern Europe, and Africa (where the study was repeated). Bettina Malnic, an olfaction expert at the University of Sao Paulo in Brazil, commented on the luck of the region study took place, saying, “if they hadn’t looked at this population, they might not have found the variant [of TAAR5].”

I am VERY sensitive to smell and, at the same time, a lover of sushi, so it definitely fascinates me that there are people out there who don’t have to deal with the odor of smelly fish. This mutation is definitely one I wish I obtained. What do you think about this? Do you think you could have this mutation?!


Meeting Your Great Great Great… Grandchildren

The MDI Biological Lab along with the Buck Institute of Research on Aging have discovered cell pathways that could increase the human lifespan by 400-500%. “The increase in lifespan would be the equivalent of a human living for 400 or 500 years.” The implications this would have are immense along with some potential drawbacks, but let’s get into the science first.

The research was conducted on C. elegans, a nematode, because “it shares many of its genes with humans and because its short lifespan of only three to four weeks.” The short lifespan allows scientists to quickly see the effects of their efforts to extend the healthy lifespan. The keyword here is “healthy” because prolonging life means nothing unless you can extend the quality as well. The scientists used a double mutant in the insulin signaling and TOR pathways. The alteration in the insulin pathway yields a 100% increase in lifespan and the TOR pathway yields a 30% increase. The incredible discovery though was that when combined the new lifespan was amplified by 500%!! The expected yield was 130%.

Image result for double mutant "

Here depicted is a diagram showing the meaning of a double mutant.

Researchers still say “the discovery in C. elegans of cellular pathways that govern aging, it hasn’t been clear how these pathways interact.” This discovery does lead to the mindset that the important methods of anti-aging are in the interactions between cellular pathways rather than singular pathways. This newly found interaction could also explain why scientists have had trouble discovering “the gene” the governs aging. The combinations of these treatments are described as being similar to the “way that combination therapies are used to treat cancer and HIV.”

It’s odd to picture a world where this treatment could be considered “cosmetic” in a way. Eventually, the human lifespan could expand to hundreds of years with some even living to 1000. The implications that this could have are a current problem we have of overpopulation. It is farfetched, but this would help immensely with the mission to expand into space. The ability to survive with hundreds of years on a potential “colony ship” allows humans to expand to other planets where we would be able to expand greatly. I’ll end with a question: If this treatment was 100% safe and affordable, would you get it? Why or why not?

How did butterflies evolve to eat poison?!

A recent article confirms that scientists have researched that caterpillars are now eating milkweed (which is supposed to kill them). How is this happening? “Scientists have unraveled the sequence of gene mutations that enabled the monarch butterfly to thrive on toxic milkweed.” We learn at a young age that caterpillars turn into beautiful butterflies, so something must be happening before metamorphosis. There are three gene changing mutation amino acid sites including, 111, 119, and 122. Mutation 122 had the biggest boost in resistance. Another article states that ‘monarch flies’ continue to have small amounts of cardiac glycosides through metamorphosis, which is a trait that has been developed in monarch butterflies to restrain predators.

Monarch butterfly eating milkweed

Monarch butterflies can eat milkweed due to a peculiarity in a crucial protein in their bodies, which is a sodium pump, that the cardenolide(steroid) toxins intervene with. How the pumps work? They move positively charged sodium atoms out of the cell resulting in the inside of the cell is negatively charged. In order for a heart to beat, the sodium pump has to build up enough electric charge and then nerves use the pumps to send signals to the brain.

Potassium pump diagram where the pump moves the sodium and potassium ions through the membrane

What does milkweed have to do with this? In the study, they first addressed how milkweed is toxic to almost all insects, but caterpillars depend on milkweed. Females use milkweed to lay eggs and caterpillars eat as much as they can before chrysalis. In the article, they are referred to as “flying poison” because the milkweed toxin gets send from their gut to their wings and anything that tries to eat it immediately vomits it up.  After these mutations, they now NEED milkweed to live and it altered the sodium pumps, so cardiac glycosides in the monarchs cells don’t affect them.

This mutation allowed butterflies to have their own food supply since milkweed is poisonous to other insects. Noah Whiteman, a biologist at the University of California, Berkely used CRISPR to try the mutations on fruit flies. The fruit fly experiment resulted in the findings that mutation 122 has bad side effects and is only useful if followed by another mutation. Other researchers say the order that mutations are done can make a big difference as well.


The Collateral Damage of CRISPR-Cas9


CRISPR’s ‘precise’ gene-editing has actually been damaging other parts of the DNA sequence, according to a recent study. Photo from this source.

Of the various gene-editing techniques, CRISPR-Cas9 is the fastest, simplest, and most accurate gene-altering method known to date. Comprised of simply two parts, CRISPR-Cas9 snips through targeted segments of DNA and causes a change in the genetic code. Scientists are hopeful that we can soon use this method to cut out mutations that code for HIV, cancer, and sickle cell disease. However, a study published in Nature Biotechnology has revealed an unwanted side-effect of CRISPR.

When using CRISPR-Cas9, there are two major molecules that create a mutation, or change, in a DNA segment. The first is an enzyme called Cas9. This enzyme works like a pair of scissors and that cuts the two helices at a specific location so DNA can be altered. The second tool used in this process is the guide RNA (gRNA) that binds to the DNA and ensures that the Cas9 molecule cuts the DNA in the correct place. Finally, after the incision, the DNA will seal itself back together, without a trace of the deleted segment.

Such a precise process seems flawless. In theory, one should be able to cut out the unwanted genetic material and our DNA should perfectly repair itself. Unfortunately, senior group leader and director of the study at Wellcome Sanger Institute in England, Allan Bradley, stated that “CRISPR is not as safe as we thought.” Through a systematic and tedious approach, Bradley and his colleagues edited a series of mouse and human cells with CRISPR and then examined DNA base pairs father and farther away from the cut site. By examining millions of base pairs, the team landed upon unsettling news.

Bradley and his team found that huge chunks of DNA were inadvertently deleted, mutated, and rearranged millions of base pairs away from the cut site. The DNA was mutated so immensely that cells lost function in 15% of cases. Because these CRISPR-induced mutations were shown so far away from the cut site, this information could have easily been overlooked in other studies.  

This research poses questions on the accuracy of such gene-editing methods. What are the long-term effects of genetic engineering with CRISPR? How can we ensure that base pairs so far away from the cut site aren’t altered? Although this is somewhat discouraging news for the CRISPR community, this newfound information is motivating more researchers to improve CRISPR technology before making it widely accessible.

Read the full article here.

Crispr-Cas9 is the gateway to a new frontier in genetic engineering. Here’s The good and the bad.

For a number of years now, molecular biologists have been diving increasingly further into the field of genome editing. The latest development into the field is the emergence of CRISPR-Cas9. CRISPR-Cas9 has risen to prominence over other potential methods of genome editing due to its relatively simple construction and low cost. CRISPR-Cas9’s original primary and intended purpose was to help fix mutations within DNA, and with this it could theoretically help eradicate entire diseases. This application of CRISPR is wholly positive, however with the increasing prevalence of the technique other potential uses have been discovered, and some of these potential uses raise profound ethical questions.

One of the main concerns of people skeptical about CRISPR is their assertion that once the door to the wholesale genetic editing of offspring is open, there is no going back. This, on its own, is a reasonable concern. The ability to choose a child’s sex, eye color, hair color and skin complexion is very likely to be made available to by CRISPR in the coming years. CRISPR does not yet have the capability to influence more abstract elements of the genome, such as intelligence and athletic ability, but this may not be far off. There are legitimate concerns that this is a slippery slope towards a dystopian society similar to the one seen in the movie Gattaca, where society is stratified into two distinct classes: those who are genetically engineered and those who are not.

Another concern raised by some scientists is the overall safety of genetic editing. A potentially very hazardous negative result of CRISPR is the possibility of an “off target mutation.” An off target mutation is the result of CRISPR mutating something other than the intended part of the genome and it could have disastrous consequences. Now, many scientists believe that with further advancements in the field the likelihood of something like an off target mutation occurring could be reduced to almost zero. However, it is important to examine the risks of any new process, and the prospect of something like an off target mutation occurring is certainly noteworthy.

For more information click here.

How DNA damaged from radiation causes cancer

In a recent study, professors from the Wellcome Trust Sanger Institute sought to see the similarity between spontaneous cancerous tumors and cancer caused by ionized radiation. By looking at the molecular fingerprint of different types of cancers, they were able to differentiate between cancers that formed by radiation and cancers that were not formed by radiation.

In the study, they studied the mutational signatures of the DNA. Mutational signatures are just ways in which the DNA is affected by cancerous mutations. They studied the DNA mutational signatures from DNA exposed to radiation, but not necessarily cancerous, and the mutational signatures of the DNA of cancerous cells of which some were caused by radiation exposure and some were not. Both included the same signatures.

The two mutational signatures that were observed were deletion of segments of DNA bases and balanced inversion, where the DNA is cut in two places, the middle piece flips around, and the pieces are joined back in the opposite orientation from before the flip. High energy radiation is the cause for balanced inversion, since it does not happen naturally in the body. After the mutation, the DNA cannot repair itself.

This gives us a better understanding of cancer and how ionized radiation affects DNA and produces these mutational signatures. Knowing this information, this helps us recognize which tumors are caused by radiation. Once we have a better understanding of this, it will prove important for determining how each cancer should be treated. But for now, this is a strong step forward in the battle against cancer and every step of the way is crucial if we are to be victorious.


Potential New Treatment Strategy for Brain Cancer!

Cancer is a disease characterized by the up-regulation of cell growth and it usually develops when normal cells are not able to repair damaged genetic material. New studies are revealing insights into the function of genetic mutations commonly found in a form of brain cancer, specifically the IDH mutation. Isocitrate Dehydrogenase(IDH) is a metabolic enzyme found in more than 70% of low grade gliomas and secondary glioblastomas, types of malignant brain tumors. In a normal cell, IDH enzymes help to break down nutrients and generate energy cells. When mutated, IDH creates a molecule that alters cells genetic programming and instead of maturing, the cell remain primitive. Studies have shown that cells holding this mutation also have an impaired ability to repair DNA. Strangely enough, low grade gliomas that have the IDH mutation are typically more sensitive to chemotherapy than those that lack the mutation. Why does this occur? We still don’t really know the answer.  Yet, researchers have discovered a potential new treatment option for the glial cells harvesting the IDH mutation– PARP Inhibitors.   A super cool future is waiting ahead.

When treating the IDH mutated cells with PARP Inhibitors, a substance in the form of a drug that blocks an enzyme called PARP, the cells were effectively killed. When the drug blocks PARP, it keeps the cancer cells from repairing their damaged DNA, and eventually they die off. The cells are extremely sensitive after the effects of the inhibitors, especially after taking the most common PARP drug called oliparib. PARP inhibitors are a form of targeted therapy–meaning the inhibitors work within a similar approach as radiation and chemotherapy– they simply damage or prevent the repair the DNA. Researchers have also found the up regulation of the unusual molecule called  2-HG(2-Hydroxyl-glutarate) within the IDH mutated enzymes. In a study with Dr. Brinda’s team at Yale, they found that 2-HG may be responsible for the defect, DNA repair inabilities, in these cells. When the production of 2-HG was blocked in these cells, the DNA repair defect was reversed and cells became unresponsive to the PARP inhibitor treatment. This finding further solidifies that PARP inhibitors may be the best new effective brain cancer treatment method. What do you think? I think this is pretty cool news!

Jto410 is the username of the radiologistwho took the picture

Low grade glioma MRI scan. Creative Commons Attribution-Share Alike 3.0 Unported license.

There are also many clinical trials occurring currently to observe 2-HG as a definite IDH biomarker for cells that are sensitive to treatment with PARP inhibitors. In addition, labs are also designing a clinical trial of olaparib and temozolomide, two PARB inhibitor drugs, in patients with low-grade gliomas. The results of these trials, are for sure going to make headlines within the Biology and Medical field! Even though, there are still many questions to answers and studies to conduct regarding brain cancer and the IDH mutation, we are definitely on the right track to cure the monster a.k.a “cancer.”

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