BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: receptor

Genetic Variation the Savior

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On April 30, 2023

In Student Post

In the article “Genetic variation in the SARS-CoV-2 receptor ACE2 among different populations and its implications for COVID-19,” published in Nature Communications, the authors explore the genetic variation in the ACE2 receptor across different populations and its potential impact on COVID-19 susceptibility and severity. The ACE2 receptor is a key entry point for the SARS-CoV-2 virus into human cells. Its expression level and genetic variants may affect the virus’s ability to infect and replicate within the host. Therefore, understanding the genetic variation in ACE2 among different populations can provide insights into the different susceptibilities and severity of COVID-19 seen across the world. The authors analyzed genetic data from various global populations and found that there is significant genetic variation in ACE2 between populations. Specifically, they identified several ACE2 variants that are more prevalent in certain populations, including a “variant that is more common in East Asian populations” and may affect the receptor’s expression level.

Microorganisms-08-01259-g001

The authors also conducted in vitro experiments – medical procedures, tests, and experiments that researchers perform outside of a living organism – to investigate the impact of these ACE2 variants on SARS-CoV-2 infection. They found that some variants, such as the one more prevalent in East Asian populations, led to reduced viral entry and replication, while others did not significantly affect viral infection. These findings suggest that genetic variation in ACE2 may contribute to the different COVID-19 outcomes observed across different populations. For instance, the higher prevalence of the ACE2 variant in East Asian populations may explain why these populations had a lower incidence of severe COVID-19 despite being initially hit hard by the pandemic. Furthermore, the author highlights the importance of considering genetic variation when developing COVID-19 treatments and vaccines. For instance, vaccines that were designed based on the original strain of SARS-CoV-2 may be less effective against strains that have evolved to better utilize ACE2 variants prevalent in certain populations. Overall, the article sheds light on the genetic variation in ACE2 among different populations and its implications for COVID-19 susceptibility and severity. The authors’ findings show the importance of taking genetic diversity into account when studying diseases and developing treatments and vaccines, particularly in the context of a global pandemic. In our recent DNA unit in class genetic variation was one of the topics of discussion, genetic variation is extremely important for the survival of a population as there is an easier chance that the species will be able to adapt and survive in different situations. Without genetic variation, many species can die out and therefore including the topic of genetic variation in viruses like covid-19 is extremely detrimental to the survival of humans when fighting this illness.

Can Your Lungs Work Against COVID-19?

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On February 28, 2023

In Student Post

Within the last two to three years there has been an immense focus in the field of science, COVID-19. This pandemic has sparked a myriad of research opportunities as well as brought up questions we didn’t even know we needed answered.

With this, recent research at the University of Sydney shows that our lungs contain a protein that blocks the COVID-19 infection and works to create a protective barrier within our body. The way it works is that a protein receptor found in our lungs sticks to the virus, and then pulls it away from the targeted cells. The protein is known as the Leucine-Rich Repeat-Containing Protein 15 or in short, LRRC15. For context, leucine is an essential amino acid for protein synthesis as well as many other biological functions. The protein is a built-in receptor inside of our bodies that binds to the COVID-19 virus and doesn’t pass on the infection.

Lungs diagram detailed

Initially, the research was published on February 9, 2023, in the PLOS Biology Journal. Led by Professor Greg Neely and his team members, the findings serve to open a new sect of immunology and COVID research, specifically around the protein, LRRC15. Moreover, it creates a path to develop new drugs and treatments to prevent infections such as COVID-19. Greely states that ” This new receptor acts by binding to the virus and sequestering it which reduces infection,” essentially the receptor is able to attach to the virus and “squish” it before it moves to infection. He also pushes the idea that the new receptor can be used to “design broad-acting drugs that can block viral infection or even suppress lung fibrosis.” Continually Dr. Lipin Loo, one of Greely’s team members, mentions, “We think it acts a bit like Velcro, molecular Velcro, in that it sticks to the spike of the virus and then pulls it away from the target cell types,” here he outlines the stickiness of both the receptor and the virus as well as the receptor’s nature to latch onto the virus and “hold” it. In addition, Loo states, “When we stain the lungs of healthy tissue, we don’t see much of LRRC15, but then in COVID-19 lungs, we see much more of the protein,” here he fronts the idea that COVID-19 lungs are far richer in the LRRC15 protein than normal lungs, this may be due to a result of the protein’s ability to immobilize the virus.

To outline COVID-19 infects us by using a spike protein to attach to a specific receptor in our cells. It mainly uses the ACE2 receptor to enter human cells. Moreover, our lung cells have high levels of ACE2 receptors, which is why being infected can often cause severe problems in our lungs. Similar to ACE2, LRRC15 is a receptor for COVID. But, LRRC15 does not support infection, instead, it sticks to the virus and immobilizes it. This prevents other cells from becoming infected. LRRC15 attaches to the spike of the virus and pulls it away from certain target cell types. The LRRC15 protein is widely present throughout our body, it is in the: lungs, skin, tongue, fibroblasts, placenta, and lymph nodes. However, the researchers observe that the lungs “light up” with LRRC15 after infection. They think the new protein is a part of our body’s natural response to combatting the COVID-19 infection. It creates a barrier that separates the virus from our lung cells most susceptible to COVID-19 infection

SARS-COV-2

To connect to our AP Bio Class, we learned about adaptive immunity where we develop an acquired immunity after being exposed to pathogens, a specific response. I see some similarity here in that the LRRC15 protein is specific to immobilizing the COVID-19 infection. Additionally, in our Cell Signalling Chapter, we focused on signal transduction and its stages, reception, transduction, and response. Specifically in the reception stage, we focused on intracellular and transmembrane receptors. I think that LRRC15 would be transmembrane in order for it to efficiently bind to the COVID-19 Spike. With this, however, I would like to see more about the transduction component of the LRRC15 receptor. Lastly in our Enzyme Unit, we learned about how different factors can affect enzymatic activity; heat, pH, and even general surroundings. I wonder which factors work to hinder and work to stimulate the purpose of the LRRC15. I invite any and all comments with additional info relevant to the topics discussed.

Is This a Possible Explanation for COVID-19’s Rapid Transmission?

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On December 30, 2020

In Student Post

In a study done by Rommie Amaro and colleagues at the University of California San Diego, Maynooth University (Ireland), and the University of Texas at Austin, it has been discovered that certain Glycans, or a sugar molecule chain bound to the SARS-CoV-2 spike proteins, could be a real reason that SARS-CoV-2 can easily enter our bodies. 

In order for a human– or a host cell– to be infected with COVID-19, the actual virus (SARS-CoV-2) must infiltrate the host cells. As SARS-CoV-2 is covered in spike proteins, these proteins dock up with a host cell receptor called ACE2, which is embedded in the cellular membrane. In order for the virus to successfully dock with the receptor, it must change its shape in order to expose the Receptor Binding Domain (RBD), or exactly where the spike protein docks with ACE2.

At the specific spike protein/ACE2 docking points, the spike proteins are covered in Glycans, or sugar molecules. These glycans have the ability to protect the virus from the host cell’s immune system. Relating the importance of the glycans and the immune system to our class, we have heavily researched the roles of sugars in molecular processes and pathways and the functions of the immune system. With this knowledge, we are able to see, recognize, and understand how powerful and prevalent the glycan is in guarding the virus against our usually strong, organized immune system attacks. As the scientists in the study processed the information about the glycans, they were intrigued to discover how it could possibly lead to easier rates of infection.

To begin, they used dynamic computer models to simulate the glycan-covered spike proteins docked to the ACE2 in the cell membrane. They were able to deduct that the glycans help optimize the spike protein’s effort to expose its RBD. Thus, the glycans actively allowed easier infection through an easier docking experience. However, they also uncovered that the glycans only bound to certain spike proteins, meaning that the immune system, but specifically antibodies, could attack the virus at these docking points. Posing as an extremely positive discovery, the absence of glycans in certain docking points inspired the team to see if they could get rid of the glycans in total. Through Biolayer Interferometry, or technology that allows you to record biomolecular interactions, they were able to successfully mutate the spike protein so it didn’t have glycans anymore– thus, reducing SARS-CoV-2’s ability to bind to ACE2. 

The concept of removing the glycans from the spike proteins has been a major point of research in vaccine production. Although vaccines being made by Pfizer and Moderna are revolved around MRNA, ideas like debilitating the virus-protecting glycans are extremely revolutionary and could lead to possible amazing breakthroughs in the future.

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