BioQuakes

AP Biology class blog for discussing current research in Biology

Author: microshoreganism

Is CRISPR the COVID-19 Cure?

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On March 20, 2022

In Student Post

New Developments In CRISPR Gene Editing Technology Show Promising Advances In Possible COVID-19 Antiviral Pill

CRISPR Gene Editing. If you have never heard of it, don’t worry, I hadn’t either. When google searching CRISPR Gene editing, I went straight to Wikipedia for the simple answer that it is a procedure done in molecular biology, in which the genomes of a living organism can be modified with extremely high precision. One of its many applications is the treating and prevention of disease, enabling researchers to edit DNA and use the natural defense system of bacteria to target and destroy the genetic material of viruses. In a new study from this summer, Dr. Sharon Lewin and her team of researchers at the Peter Doherty Institute for Infection and Immunity at the University of Melbourne believe they may have harnessed CRISPR’s gene editing abilities to block the replication of COVID-19. 

Very similar to the replication of DNA, RNA replication begins with a single strand of “Template” RNA. In DNA, because it can only be replicated in one direction (5’-3′), and the strands run antiparallel, each strand is built in opposite directions creating one leading strand and one lagging strand. However, RNA only needs one strand made because it is single-stranded instead of a double. In SARS-CoV-2, an enzyme called RNA-Dependent RNA Polymerase adds nucleotides in the 5’-3′ direction, replicating the template RNA. Because humans have DNA, we don’t copy RNA; instead, we transcribe it to make proteins. Therefore this RNA replication process does not occur in humans and only in viruses.

Lewins’ team designed the gene editing to target single strands of RNA, like those found in COVID-19. CRISPR is most commonly associated with Cas9, an RNA-guided enzyme that cleaves foreign nucleic acids. However, Lewin and her team used a different enzyme, Cas13b, which could cleave RNA instead. Targeting specific sites on the RNA strands of SARS-CoV-2, Cas13b binds to the RNA and destroys the part of the virus needed to replicate, “Once the virus is recognized, the CRISPR enzyme is activated and chops up the virus,” said Lewin. She continues to explain that although the COVID-19 vaccines are highly effective, there is still a clear and urgent need for treatment once the disease is contracted. The ideal treatment would be an antiviral drug that could be taken shortly after the patients tested positive for COVID-19, “That’s what we hope to achieve one day with this gene scissors approach.” 

CRISPR Cas9 technology

Having written in previous blog posts about my mother’s struggles with COVID-19, my dad also had a very different yet real struggle. Like most people, my dad, having somehow not contracted COVID from my mom at the beginning of quarantine, was very fearful of getting sick himself. Fortunately, my dad has still never had COVID (knock on wood). This is great because he has remained healthy; however, it also had downsides. For my brother and me, being both kids and relatively healthy, when we contracted COVID in mid-August, it was nothing more than a rough cold. A cold that, after ten days, not only was gone but enabled me to feel some sense of temporary immunity to the virus and allowed me to feel comfortable going out with friends and returning to some level of normalcy. My dad never got this. Because he never contracted COVID, he lived a completely secluded life until this past February (when he gave up and began going out in public). If my family and I went to a mall, he would wait in the car. If we ate out, he would wear a mask the whole time and not eat until we got home. The fear for my dad was not specifically getting covid but not having some antiviral drug to take once he contracted the virus. A solution like Dr. Lewins would have been and still would be a life-changer for many families who still live in fear of getting sick from COVID-19.  

Although this breakthrough in RNA CRISPR technology is remarkable, the study was performed in lab dishes and is still waiting for testing on animals or humans. Additionally, CRISPR technology medicines have not been approved to treat any diseases. Unfortunately, we are probably a couple of years away from a widely available treatment. 

Can Your Eyes Save Your Brain?

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On February 16, 2022

In Student Post

Are Retinal Tests Able to Identify Early-Onset Alzheimer’s?

According to The Alzheimer’s Association, In 2021, 6.2 million Americans were living with Alzheimer’s Disease. 1 in every 9 people (11.3%) above the age of 65 has Alzheimer’s Disease, and these percentages only increase with age, leaving 35 percent of people above the age of 85 with Alzheimer’s or Dementia. For those who do not know, Dementia is a general term for the loss of memory and other thinking abilities, severe enough to interfere with daily life. Alzheimer’s is the most common type of Dementia, and it affects not just memory but behavior. Mainly recognized in adults above the age of 60, our current form of diagnosing Alzheimer’s is waiting until people become overly forgetful or begin to act out of character. Although early detection is occasionally possible through brain scans, this method is expensive and unsuitable for most. 

My uncle Steven was only 51 when he was diagnosed with Alzheimer’s. Although caught decently early, his changes in behavior and short-term memory loss were apparent. Often asking a question only minutes after he had previously been told the answer, my family was devastated. Before being diagnosed, my uncle was the CFO of a Fortune 500 company and was always seen as a mentally and physically strong man. Having no choice but to retire young and focus on his health was a hard truth for all of us to accept. 

Alzheimer's Disease

Sad and confused about how this had happened, I did extensive research on the causes of Alzheimer’s. Although there are multiple possible causes and factors that play into the development of Alzheimer’s disease, one way is through inheritance. Early-onset Alzheimer’s diseases, like my uncle’s, can be inherited genetically. Humans typically have 46 chromosomes in each cell of their body. Each of these chromosomes contains anywhere between 20,000 and 250,000 genes. Usually having two copies of each chromosome, one copy comes from the mother’s egg and the other from the father’s sperm. Each egg and the sperm are haploid, meaning they contain 23 chromosomes. When the sperm fertilizes the egg, two copies of each chromosome and gene are present. Although some genes are required from both parents to be passed onto their offspring, Alzheimer’s is inherited in an autosomal dominant pattern. This is one of the many ways that disorders can be passed down through families, and it means that only one parent needs to have the abnormal gene for you to get the disease. Thus people who inherit one copy of the APOE e4 allele have a significant chance of developing Alzheimer’s. However, those who inherit two copies of their allele are at even greater risk. It is important to note that not all people with the disease have the e4 allele, and not all people with the allele develop Alzheimer’s. Because in most cases, an infected person inherits the gene from an infected parent, it is not likely that my uncle developed Alzheimer’s genetically as no one else in my family tree ever had the disease.

Autosomal dominant inheritance

Moving forward with my research, I looked into possible treatments; unfortunately, most drugs are still in trial or only applicable to individuals diagnosed before any level of severe memory loss occurs. While this is a sign of good progress, I can’t help but feel there must be some better solution to diagnose Alzheimer’s before it becomes too late. Thankfully, Dr. Ashleigh Barrett-Young and her team agreed.

Working at Otago’s Dunedin Multidisciplinary Health and Development Research Unit, Barrett-Young and her team of researchers have investigated the retina’s potential to indicate Alzheimer’s earlier in life. As stated by Barrett-Young, “In the near future, it’s hoped that artificial intelligence will be able to take an image of a person’s retina and determine whether that person is at risk for Alzheimer’s long before they begin showing symptoms, and when there is a possibility of treatment to mitigate the symptoms.” The Dunedin study analyzed the retinal nerve fiber layer (RNFL) and Ganglion cell layer (GCL) of 865 people at the age of 45. Dr. Barret-Young and her team reported that thicker RNFL and GCL were associated with better cognitive performance, while a thinner RNFL was linked to a more significant decline in processing speed. Adding to their report, “These findings suggest that RNFL could be an indicator of overall brain health. This highlights the potential for optical scans to aid in the diagnosis of cognitive decline.” Since treatment for Alzheimer’s is yet to be discovered, the ability to identify the disease in preclinical stages could allow the possibility of aid before it’s too late. Although further studies are required to determine if retinal scans can predict precisely Alzheimer’s, or just the expected cognitive decline of the brain, researchers have hope. 

So, while this solution sadly offers no benefit to my uncle, I feel hopeful that this new diagnosis technique will be beneficial for the millions of people who would have had family members or friends combating Alzheimer’s disease but caught it early enough to intervene and do something about it. 

14 Days or 14 Months?

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On December 20, 2021

In Student Post

The Infamous “14-day” COVID-19 Illness Has Still Not Ended for Some.

Approximately one in four COVID-19 patients appear to have lingering symptoms, even after they have fully recovered from the virus, says the University of California Davis Health. Known as “Long Haul Covid,” it has been relatively unknown why each person’s immune response differs drastically. 

Feeling sick just two days after the world closed on March 11, 2020, my mom began to show all the symptoms of COVID-19. Tests were scarce, and by the time she was able to get one, it came back negative. However, she dealt with the severe and immediate symptoms of COVID-19 for six months straight. She maintained an on and off fever for months and has still not regained her taste or smell. Unsure of why everyone around her (including myself) contracted the virus and recovered after a mere 14 days, she searched for answers everywhere.

Luckily Dan Longo, Professor of Medicine at Harvard Medical School, published an article this past week in which he thinks he has discovered the reason. Antibodies mimicking the virus. You see, our body has a particular system for how it typically handles viruses.

When pathogens pass the body’s barrier defenses, they trigger innate cellular defenses. In the area of entry, Mast cells release histamine and macrophages (large phagocytic cells), which secrete cytokines. These cytokines attract dendritic cells, which engulf the bacteria (COV2 virus) and fuse it with a lysosome to break it down, preserving the foreign antigen (epitope). The dendritic cell will then display the foreign antigen on an MHC protein on the cell’s surface. A T-helper cell will then come and identify the foreign antigen. Now activated, the T-helper cells will release interleukin (a cytokine) to signal the beginning of the cell-mediated and humoral response. In the Cell-Mediated immune response, the T-helper cells will stimulate other T-cells to divide and create two types of cells. T-memory cells will circulate your body to prevent reinfection, and Cytotoxic T-cells will kill any infected cells. In the Humoral Response, B cells will bind to the antigen on the virus and recognize it, while selected B cells will be stimulated by T-helper cells and divide. The divided B cells will become B plasma cells whose job is to secrete antibodies that bind to and neutralize the pathogen. Or B-memory cells whose job, much like the T-cells, is to circulate the body, preventing reinfection. 

Primary immune response 1

In regards to COVID-19, however, why hasn’t our immune response been consistent for everyone? Longo’s article answers that by closely drawing upon the concepts of Nobel Laureate Niels Jerne’s Network Hypothesis, in which she states that, as usual, the B-plasma cells produce protective antibodies in response to an antigen. However, these same antibodies later trigger a new antibody response, only this time toward themselves. These secondary antibodies are called anti-idiotype antibodies, and they are created when one antibody binds to the set of unique epitopes of another antibody. These secondary antibodies bind to and deplete the initial protective antibody response, mirroring the original antigen itself. Quoted from Longo’s research partner UC Davis Vice-Chair of Research and Distinguished Professor of Dermatology and Internal Medicine William Murphy, “A fascinating aspect of the newly formed anti-idiotype antibodies is that some of their structures can be a mirror image of the original antigen and act like it is binding to the same receptors that the viral antigen binds. This binding can potentially lead to unwanted actions and pathology, particularly in the long term.” Binding to the ACE2 receptor, an angiotensin-converting enzyme identified as the receptor for the SARS-CoV-2 viral entry, the anti-idiotype antibodies could affect normal ACE2 functions. With a lack of research surrounding the theory, Murphy states that he believes some of the long-lasting effects of COVID-19 reported result from the critical tasks of ACE2 being tampered with. In terms of the vaccine, most of the research studies on antibody responses focus on initial protection instead of long-term effects. Thankfully, Longo concludes by saying that most of Murphy’s and his questions are testable and can be at least partially tested in their laboratory.

anti-idiotype antibody

It has been 21 months since my mom first contracted COV2, and thankfully she is doing much better. However, causing much frustration, she has not fully recovered. Similar to an autoimmune disease, she has periods where she feels fantastic and periods when she struggles. And so, while the information about Long Haulers Covid has increased dramatically, it is evident that there is still much to learn. 

Have We Discovered The Itchy Stitch?

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On October 27, 2021

In Student Post

A Brand New Poison Ivy Vaccine is in the Works; here is What We Know So Far.

Vaccine: The word spoken and heard by most Americans at least ten times daily this past year, yet not usually preceded by “Poison Ivy.” Working at Duke University, biochemist Sven- Eric Jordt heads a team of researchers investigating pain and itch mechanisms, studying the unpleasant sensations of Toxicodendron radicans, better known as poison ivy. Jordt reveals that contact dermatitis (the red rash received from poison ivy) is usually treated by local doctors and rarely shown attention or mass funding. Author of ‘A Vaccine Against Poison Ivy Misery Is In The Works,’ Claudia Wells states, “given the toll in suffering and dollars, you would think serious attention would be paid to this worsening public health issue, you’d be wrong.” When pharmaceutical companies recognized more money was to be made on drugs for chronic skin conditions like eczema, they felt no need to research effective treatments on a temporary rash.  

Toxicodendron radicans (poison ivy) 2 (49046043216)

Having never personally contracted poison ivy, I cannot describe the exact feelings of pain or irritation, but to quote a good friend, “it would be less painful for my skin to be set on fire.” Now I must state that this friend did have an extreme reaction to poison ivy, they pitched their tent in a field of the poisonous plant, yet severe reactions are more common than most might assume. Every year 10 – 50 million Americans contract poison ivy and suffer for an average of 2-3 weeks. Research obtained in a six-year study at Duke University found that an increase of carbon dioxide, i.e., climate change, causes the poison ivy plant to produce a more potent allergenic form of Urushiol, the resin responsible for the rash. With increased concerns regarding climate change, it appears odd that Jordt is one of few who take this rash seriously.

 Currently, the main treatment methods of antihistamines and cortisone cream do the rash very little justice. This is because our body’s reaction to Urushiol has no relationship to histamines, rendering antihistamines useless. In explaining this information to my dad, he agreed that all of the efforts recommended to him when he got poison ivy, a little less than two years ago, proved ineffective. To solve this, Sven Jordt and his colleagues began to analyze receptors that matched with proteins that showed inflammation from Urushiol.

In biology, receptors are proteins that receive signals by bonding with molecules known as ligands to send a specific message onward. A cell’s response depends on the types of receptors present, and each cell has its own number and type of receptor that allows them to act differently to various stimuli. Regarding poison ivy, Jordt and his team discovered that interleukin 33, an immune chemical in the body, is the main culprit behind the symptom of itchy skin. Jordt and his team of researchers are currently testing antibodies against IL-33, such as ST2, in primary sensory neurons. If ST2 could effectively block IL-33’s receptors, the necessity to scratch would virtually disappear. “This is all very new information,” Dermatologist Brain Kim, co-director of the Center for the Study of Itch & Sensory Disorders at Washington University in St. Louis, states. In the past, scientists believed that both the rash and itch from poison ivy were triggered by the immune system’s T cells. Further studies, however, have shown that the inflamed rash and itch sensation come from two different places entirely; It is believed “T cells do cause the inflamed rash of poison ivy but that these other pathways provoke the itch.” (Brian Kim)

 While human research has been challenging to complete due to a lack of study funding, a compound called PDC-APB, a small synthetic molecule derived from active urushiol components, is being developed into a vaccine to prevent painful contact dermatitis.

 As stated earlier, I have thankfully never had poison ivy myself, and I would like to keep it that way. As someone who goes on Sunday hikes through the woods with my family, contracting poison ivy is a constant fear of mine and leaves me wearing pants while walking in the July heat. I think a vaccine would be a fantastic option for someone who spends much of their time in places of possible poison ivy. The only question would be, is this the solution to our itchy problem?

 

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