BioQuakes

AP Biology class blog for discussing current research in Biology

Author: Joshmosis

Analyzing Viruses in One Step Using LUNAS

In this article from the American Chemical Society, Maarten Merkx and his colleagues research how to use and combine CRISPR-related proteins with a bioluminescence technique whose signal could be detected with a digital camera. This new technique can diagnose illnesses faster while being much more efficient and practical. Bioluminescence is a chemical reaction involving the luciferase protein that causes the luminescent, glow-in-the-dark effect. The luciferase protein has been incorporated into sensors that emit an easily observed light when they find their target, but they lack the incredibly high sensitivity required of a clinical diagnostic test.

Mareel - Bioluminescence in Norra Grundsund harbor 2

CRISPR, a gene-editing technique, has the ability to increase sensitivity, but it requires many steps and additional specialized equipment. With the new technique, called LUNAS (luminescent nucleic acid sensor), two CRISPR/Cas9 proteins specific for different neighboring parts of a viral genome each have a distinct fragment of luciferase attached to them. If a specific viral genome that the researchers were testing for was present, the two CRISPR/Cas9 proteins would bind to the targeted nucleic acid sequences and come close to each other, allowing the complete luciferase protein to form and shine blue light in the presence of a chemical substrate. RPA-LUNAS successfully detected SARS-CoV-2 RNA within 20 minutes, even at concentrations as low as 200 copies per microliter.

This is similar to the process of gene regulation that uses an inducible operon as we learned in class. An inducible operon is a type of negative regulation that turns on when it interacts with an inducer. It is usually off which means there is an active repressor that binds to the operator to block the RNA polymerase from transcribing the DNA. When there is the inducer, such as the virus, the inducer inactivates the repressor by binding to the allosteric site which allows the RNA polymerase, such as the CRISPR/Cas9 proteins, to transcribe and eventually produce the protein, such as the luciferase protein.

As we are recovering from the devastating COVID-19 Pandemic, how can new medical advancements and technology help us prepare for future outbreaks?

Revolutionizing Photosynthesis: The Power of Rubisco Enzyme Engineering

Enzyme engineering has the power to create several new discoveries and possibilities in the evolutionary field. Questions that were not answerable through decades of really hard biochemistry have now become accessible by integrating this evolutionary perspective. In the past, Rubisco faced many issues, such as starting to catalyze an undesired reaction, in which it mistakes O2 for CO2 and produces metabolites that are toxic to the cell. In the article by the Max Plank Society, researchers have discovered that the Rubiscos that show increased CO2 specificity recruited a novel protein component of unknown function, through resurrecting and studying billion-year-old enzymes in the lab using a combination of computational and synthetic techniques.

According to this article by Alejandra Manjarrez that analyzes that research, form I rubisco has the highest specificity for carbon dioxide and the most efficient catalytic activity. Form I Rubisco is made up of eight identical catalytic large subunits and eight identical small subunits. Researchers suspected that its enhanced ability to discriminate CO2 from chemically similar molecular oxygen could be related to the presence of these small subunits since no other forms of Rubisco have them.

1aa1

For years, research focused on changing amino acids in Rubisco itself, but new findings suggest that adding new protein components to the enzyme could be more productive. Rubisco is the most prevalent enzyme on the planet and is the key enzyme responsible for photosynthetic and chemoautotrophic carbon fixation and oxygen metabolism. It catalyzes the fixation of atmospheric CO2 to ribulose-1,5-bisphosphate (RuBP) to form two molecules of 3-phosphoglycerate (3PGA). This is the first part of the Calvin cycle which, as you learned in class, involves using atmospheric carbon dioxide, ATP, and NADPH to create G3P, which is the building block of glucose, through the processes of carbon fixation, reduction, and regeneration of the CO2 acceptor. With the new improvements in the efficiency of Rubisco and enzyme engineering as a whole, plants may be able to combat the increasing amount of carbon dioxide emissions hurting the earth through improved photosynthesis.

A New Way to Predict COVID-19?

SARS-CoV-2 without background

According to this article from the Karolinska Institutet, its researchers believe IL-26(Interleukin-26) is a possible biomarker for acute COVID-19 because of its correlation with patients with acute COVID-19 infection in conjunction with its correlation with an exaggerated inflammatory response.

IL-26 is an inflammatory mediator and a driver of chronic inflammation because of its ability to act as a carrier of extracellular DNA, and as an antimicrobial molecule through its capacity to form pores in bacterial membranes.

In addition, this article from the Yale School of Medicine states that high levels of neutrophils, inflammatory cells, are a biomarker for COVID-19 patients who become severely ill. The article also connects COVID-19 with obesity, believing obesity increases the risk of severe illness from COVID-19. Another biomarker is thrombomodulin, a soluble form of a protein on the surface of endothelial cells, which was highly correlated with survival among all COVID-19 patients

Here is an image of a neutrophil:

Blausen 0676 Neutrophil (crop)

 

In an older article regarding biomarkers for the early stages of COVID-19, Professor Burkhard Becher and his team at the Institute of Experimental Immunology at the University of Zurich discovered that the number of natural killer T cells in the blood is a biomarker to predict the severity of the disease. As you learned, killer T cells, also known as Cytotoxic T Cells, are part of the Cell-Mediated Response to kill infected or cancerous cells. In this case, these T-cells help fight against the cells infected with SARS-CoV-2 to get rid of the virus from the body. The reason the vaccine is so important is that it creates memory cells that help prevent reinfection and improves the body’s reaction to the virus

Here is an image of a T-cell:

Healthy Human T Cell

Biomarkers are significant because they give us an understanding of what the virus does to the body and how the body reacts to it. This information can be used to help find early suspicion of disease, confirm disease severity, classify the disease, rationalize therapies, assess response to therapies, and predict the outcome. I believe that by being able to better analyze COVID-19 using these biomarkers, we will eventually be able to control the spread of the virus and end this pandemic we are facing.

Do you think the COVID-19 virus will have another surge or will it lessen and continue to infect us similar to influenza?

AlphaFold: Is Artificial Intelligence Taking Over?

In this news article by  she talks about a new deep-learning artificial intelligence system called AlphaFold. The purpose of this new technology is to predict the 3-D shapes of proteins by recognizing patterns in structures. At its first release in 2021, the AlphaFold included predictions for most known human proteins, with predictions of over 350,000 protein structures. Since its initial release, the AlphaFold database has increased the number of protein structure predictions to over 200 million.

Confidence alphafoldAF-Q63HQ2-F1

As you can see by the model, some parts of the prediction are more or less accurate than others. One of the main issues with AlphaFold is the fact that these are only predictions. Scientists cannot use this information with full confidence and require further experiments to be able to be confident in the findings. Even with this issue, scientists and researchers have been able to develop potential new vaccines, improve their understanding of diseases, and gain insight into human evolution with this new artificial intelligence system.

As you may remember from your AP Biology class, protein structures are extremely important in allowing the protein to perform its job. Proteins are extremely integral in your body’s ability to function. Enzymes are used to speed up reactions, antibodies protect our body from diseases, hormones send signals to the body, etc.  By knowing the structure of the protein, scientists gain a better understanding of how proteins and all of these processes work. Just by changing one amino acid, the whole structure changes which can cause diseases such as Sickle Cell Anemia. If you would like to learn more about other important purposes of protein structure, this article goes into more in-depth on the applications of protein structure and modeling.

Now onto the topic of artificial intelligence as a whole. While artificial intelligence can reduce human error, take risks instead of humans, create unbiased decisions, and automate repetitive actions, it also has several downsides(besides the possibility of it becoming sentient and taking over the world like in movies). Some of these are having high costs, increasing the amount of unemployment, being emotionless, having no morals, and making humans lazier. Artificial intelligence has the potential to completely change society as a whole. I believe that as long as we are able to keep artificial intelligence under control and not let it get into the wrong hands, it will be a great benefit to society through important breakthroughs, such as AlphaFold, and new ideas that would have never been thought of without the use of this technology.

Do you believe artificial intelligence will be the salvation for humanity or will it be its downfall?

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