anbhatia – BioQuakes

Author: anbhatia

CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, is a gene editing tool comprised of DNA sequences from prokaryotes, that is becoming more commonly used to treat and potentially cure life-threatening diseases that have previously been viewed as a death sentence; in December of 2022, a study was conducted at the University of California San Diego School of Medicine, where it was discovered that CRISPR technology can be used to target the gene that causes Huntington’s Disease.

First, we must understand what exactly Huntington’s Disease is. Huntington’s Disease, which was discovered in 1872, is a rare neurological disorder characterized by the gradual destruction of nerve cells in the brain. It is caused by a single defective gene, and this mutation is as dangerous and tragic as it is rare; the disease has no cure, and patients typically do not survive beyond 20 years post-diagnosis.

However, thanks to CRISPR, it is a very real possibility that that will soon change.

The study that was conducted at U.C. San Diego involved the experimentation of Cas13d – an RNA editing technique – against toxic RNA and protein buildup that is associated with the HTT gene mutation that causes Huntington’s Disease, and the trial was found to be successful in terms of eliminating that buildup. The experiment was conducted on mice, and it was also discovered that only one injection of the Cas13d therapy was necessary to yield results, and the benefits (improved motor function, lessened symptoms) lasted for eight months.

This discovery is especially fascinating as it connects to our AP Biology units in terms of mutations: The most common genetic mutations are insertions, substitutions, and deletions. The mutation that causes Huntington’s Disease, however, fits into neither one of these categories: if anything, the mutation is considered a duplication, as it is characterized by the unwanted repetition of cytosine, adenine, and guanine; these repetitions are what lead to the protein buildup, and damage the HHT gene.

In previous years leading up to the U.C. San Diego experiment, trials conducted to target the gene that causes Huntington’s Disease have mostly been unsuccessful, but we can hope that this new discovery is a step in the right direction and may provide the key to figuring out how to treat this disorder that has historically been viewed as a death sentence.

Biological Warfare: Bacterial Edition

By anbhatia

On March 15, 2023

In Student Post

In February 2023, a study was published announcing that bacteria possess something similar to humans that can activate and deactivate immune pathways, and therefore this “something” could be used to cure diseases; that “something” is called the ubiquitin transferase enzyme.

Biological warfare, the use of infectious agents to kill diseases caused by other infectious agents, has been considered as a potential solution in the past. In fact, years prior, a family of DNA sequences now referred to as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) were discovered in bacteria, and it was determined that these sequences were capable of killing other phages and being used to cure infections.

Our immune pathways, as we learned in our immunity unit in AP Biology, is crucial for our survival as a species. Our immune system consists of innate immunity, involving natural killer cells that serve as our first line of defense against pathogens, and adaptive immunity, involving B cells and T cells that need to be trained to fight these pathogens. Our immune pathways alone, however, cannot rid us of neurodegenerative diseases, and these diseases still unfortunately have no cure..

One may be wondering now, how can the ubiquitin transferase enzyme work to treat diseases like Parkinson’s? How does it help our immune pathways? Well, the answer to that is protein editing. The enzyme contains two proteins, CD-NTase-associated protein 2 and 3 (also known as Cap2 and Cap3); these proteins are what serve as the activation and deactivation for immune pathways: they can direct old, unnecessary, or damaged proteins to be broken down.

When the potential of CRISPR was discovered, scientists used genome editing to direct the machine so it would kill its targeted diseases. A similar attempt could be made with the ubiquitin transferase enzyme.

Finding the existence of this in bacteria especially is an amazing discovery, as not only does it propel us in the right direction in terms of potentially curing Parkinson’s or other neurodegenerative disorders, but it connects back to our other lesson in AP Biology that humans and bacteria are not so different after all. We share about a thousand genes!

It is particularly interesting knowing how biological warfare could be used to help us.

20 VS. 4- A Universal Flu Vaccine

By anbhatia

On January 17, 2023

In Student Post

20 VS. 4- A Universal Flu Vaccine

Every autumn, it’s the same routine: scientists predict which 4 or 5 strains of influenza will be circulating in the coming months, prepare a vaccine, and those who want it get it; sometimes the predictions are accurate, and people are spared from the virus, but other times it is not.

As we have learned in AP Biology, the human body has both innate immunity and acquired immunity to protect against diseases; vaccination is a form of artificially acquired immunity, in which a vaccine introduces the immune system to proteins from a virus; this trains the immune system to produce antibodies against the virus, so it knows how to encounter the actual virus later, should it be necessary. Unfortunately, when it comes to the flu vaccine, the antibodies that we are trained to produce from the vaccine are often not a match for the circulating flu strains, which causes the vaccine to be less effective.

But what if there were a way around this? Suppose that, instead of having to play a delicate guessing game as to which flu viruses are circulating more than others, there was a single, comprehensive vaccine that could provide immunity for multiple strains at once. This may be a real possibility in the near future; in November 2022, a research team at the University of Pennsylvania designed an influenza vaccine using mRNA technology, and when tested in mice and ferrets, was discovered to protect against 20 different strains of influenza.

One may be wondering, how could such a feat be possible? Well, we must look at how this specific vaccine was designed; it was made in a very similar fashion to the COVID-19 Pfizer and Moderna vaccines, using mRNA technology. When a person takes the Pfizer or Moderna vaccine, mRNA is introduced into the person’s body, triggering their cells to recreate a harmless version of the spike protein, causing the person’s immune system to recognize it and therefore learn how to create an efficient immune response against the virus.

The fact that this has been seen in the COVID-19 vaccine makes it easier to understand why the mRNA vaccine created for influenza was effective in mice. This is very different from the traditional influenza vaccine, which involves injecting an unactivated or weakened version of the virus into the body; while it is a formidable opponent against the influenza when the strains are a match, the design of traditional vaccines have been found to be less protective than mRNA vaccines.

The experimental 20-strain influenza vaccine has yet to undergo human trials, but it does provide some optimism looking into the future of flu seasons.

BQ- Outsmarting Bebtelovimab

By anbhatia

On December 8, 2022

In Student Post

On November 30, 2022, the FDA released a statement stating Bebtelovimab, an antibody treatment previously approved to work against COVID-19, has now lost its authorization status, due to the presence of new Omicron subvariants, BQ.1 and BQ.1.1, which are believed to be capable of avoiding this antibody treatment.

But, how are BQ.1 and BQ.1.1 able to avoid the treatments? Well, this can be traced back to the spike proteins themselves.

When the SARS-CoV-2 virus enters the body, it is able to bind to the ACE2 receptors and therefore be able to multiply and spread its genetic material to other cells in the body. Thanks to the development of the COVID-19 vaccine, however, our bodies are essentially programmed to respond the same way we would to an actual infection. As a result, we produce antibodies that learn to recognize the spike protein and therefore fight against it. This connects back to our lesson in AP Biology about immunity acquired from infection and vaccination.

However, the COVID-19 vaccine was made to protect against the original strain of the virus only (using the original spike protein), thus leaving people defenseless against mutations of the virus, such as Delta and Omicron. This is specifically happening with the newest subvariants, as BQ.1 has mutations of the spike proteins that our bodies don’t recognize as well.

Recently, a bivalent version of the vaccine was released to the general public to protect against other mutations of COVID-19 as well, including Omicron. The vaccine does provide protection against the original Omicron variants found at the end of 2021 and beginning of 2022, but because of BQ.1 and BQ.1.1 both having even more dissimilar spike protein mutations, they are able to bypass our antibodies produced by the vaccine, even faster than other subvariants of Omicron.

As a result, it is no surprise that the antibody treatment was pulled by the FDA; considering the variants can even bypass the newest boosters, they would likely be resistant to antibody treatments that were made to treat previous variants of COVID-19.

But this decision made by the FDA leaves us with even more unanswered questions than before: without Bebtelovimab approved for usage, what will happen to those hospitalized as a result of the new subvariants? And what about those who become hospitalized with previous subvariants? What will be their best chance?

You Survived The Black Death… But At What Cost?

By anbhatia

On October 24, 2022

In Student Post

As we all know, the Black Death, which occurred from 1346 to 1352, is regarded as the deadliest plague in human history. It killed about a third of the Earth’s population and survivors were left with physical and emotional scars. However, one of the most wondered aspects of this pandemic was how so many people still managed to survive, since the plague came with a 30-60% chance of death. Today, though, we know that genetic variants in people at the time granted their bodies a stronger ability than others to fight off the disease or even avoid it. Those survivors, thanks to Charles Darwin’s evolutionary theory of survival of the fittest, were able to pass down those genetic variants; however, what is not commonly talked about is how these genetic variants currently affect the descendants of the Black Death survivors.

Recently, it has been discovered that the same genetic mutations that saved civilians in the 14th century from the plague are now the same ones that are increasing civilians in the 21st century’s risk of disorders such as Crohn’s Disease.

The two genetic variants most credited with providing protection against Yersinia pestis, the bacteria that causes the bubonic plague, are ERAP2 and NOD2. Both of these genes have been proven to assist the body and immune system in fighting off the infection faster, and have been passed down generation to generation thanks to the survivors of the plague. However, it has also been discovered that these genes are linked to Crohn’s Disease. Crohn’s Disease is an inflammatory bowel disease that causes swelling in the digestive tract, and a major risk factor of the disease is NOD2. It has also been recently suspected that ERAP2 is also causing individuals to be genetically predisposed to Crohn’s Disease. While ERAP2 does not increase a person’s chances of developing Crohn’s, it is still something to be concerned about, especially since NOD2 has already also been identified as a risk factor for several years.

In conclusion, it is safe to say that while the Black Death may be over, the long term ramifications of it are most certainly not and there is still more information to be found as to how these ramifications present themselves today.

How do you feel about these new findings surrounding the Black Death and the revelation that what could save someone from it hundreds of years ago could be the same thing that puts someone at risk to another disease today?

BioQuakes

AP Biology class blog for discussing current research in Biology

Author: anbhatia

A Potential Cure: We’ve Waited 151 Years For This!

Biological Warfare: Bacterial Edition

20 VS. 4- A Universal Flu Vaccine

BQ- Outsmarting Bebtelovimab

You Survived The Black Death… But At What Cost?

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