rileybosome – BioQuakes

Author: rileybosome

As we have learned in AP Biology class, the spike protein, or S protein, is located on the surface of SARS-CoV-2 is linked to transmissibility and cell entry. Located on the S protein is the receptor-binding domain (RBD) which is a key factor that allows the virus to dock to body receptors and invade host cells. Effective antibody therapeutics target S proteins.

Due to their small size and ability to penetrate into lung tissue, nanobodies have been speculated to be an excellent source for novel COVID-19 antibody therapeutics. A recent study measured these proposed capabilities for potential usage as a treatment. The proposed therapeutics would be used in veterinary medicine and aim to directly prevent SARS-CoV-2 pseudoviruses from compromising host cells.

The researchers screened and sequenced specific nanobodies, then, they were produced and amplified. The study validated the speculation by observing the carefully selected nanobodies bind to the SARS-CoV-2 S protein and RBD protein simultaneously. 85% of pseudoviruses were observed to be inhibited in a solution with 100mg of nanobody concentration.

What makes nanobodies even more attractive for usage in veterinary medicine is that its inexpensive to produce and can be made in large amounts. Given these beneficial qualities of nanobodies, they seem to be a plausible and favorable COVID-19 treatment.

How Gene-edited Strawberries are Safe and Beneficial to the Consumer

By rileybosome

On March 16, 2022

In Student Post

Over one-third of purchased strawberries end up getting thrown in the trash due to bruising, mold, or mushy texture. However, The J.R. Simplot Company and Plant Sciences Inc. hope to change this outcome. The pair of companies plan to modify the DNA of strawberries with the help of CRISPR-Cas9 and sell them on a commercial scale— and don’t worry! Recently published research suggests that it is safer than other alternatives.

These gene modifications aim to extend strawberry shelf life, prolong its growing season, and reduce consumer waste. This essentially means that farmers can efficiently grow more quality fruit for longer portions of the year.

CRISPR-Cas9 is a tool derived from the immune defense system in Streptococcus Pyogenes bacteria and is currently repurposed to edit sections of DNA sequences. CRISPR-Cas9 or the CRISPR/Cas9 system is primarily made up of the Cas9 protein, crRNA, and tracrRNA (or, more simply, guide RNA).

As we have learned in AP Biology, RNA is a single-stranded molecule crucial to the processes of coding, decoding, regulation, and expression of genes. Our initial understanding of RNA holds to be true as the human-engineered guide RNA from the CRISPR/Cas9 system dictates exactly where the protein to cuts in the sequence. After the targeted section is cut, the Cas9 protein removes the particular section of DNA. Then, Host DNA can be placed in the removed portion of the DNA sequence and elicit a desired trait in the gene. For a deeper explanation of how CRISPR-Cas9 functions, I recommend watching Paul Andersen’s YouTube video on the subject.

This is exactly how The J.R. Simplot Company and Plant Sciences Inc. plan to genetically modify the genes within the strawberry.

This technology is far more efficient than the cumbersome process of selective crop breeding. To boot, Plants modified by the CRISPR/Cas9 system were found to be nearly identical to plants bred using traditional methods. The CRISPR/Cas9 system has also been found to have been thousands of times less likely to target the wrong stretch of DNA, making it potentially much safer than alternative methods of gene editing.

In the near future, The Simplot and Plant Sciences Inc. team plan to sell the strawberries after they identify the key genomes that determine shelf life and edit the plants for ideal crops.

Do you think this is exciting news? Would you try a gene-edited strawberry? Why or why not?

Could Sharks be the Solution to Ineffective SARS-CoV-2 Antibody Treatments?

By rileybosome

On February 16, 2022

In Student Post

Sharks are often associated with gruesome stories of attacks and horror. However, lead researcher at the University of Wisconsin-Madison School of Medicine and Public Health, Dr. Aaron LeBeau believes sharks deserve to be recognized in a more positive light– due to their potential for creating advanced neutralizing antibodies (NAb) therapeutics for treating SARS-CoV-2.

Neutralizing antibodies have demonstrated efficacy in treating SARS-CoV-2 in previous trials. In the recent past, the FDA authorized two NAb therapeutics for emergency use for SARS-CoV-2. However, the effectiveness of these two treatments has been complicated by the development of new variants with highly mutated target antigens. These naturally occurring mutations in the target antigen result in insufficient neutralization of the virus when using those current therapeutics derived from classical human antibodies.

This is news for concern as genome sequencing exposed the virus to create two single-letter mutations each month.

As we learned in our AP Biology class, mutations to proteins such as SARS-CoV-2 antigens occur within the amino acid chains in the protein’s primary structure. These changes in chemicals could alter the kinds of covalent or ionic bonds in the protein’s tertiary structure. This, of course, changes the antigen’s three-dimensional shape. This is why the original NAbs have experienced diminished performance as new variants emerged. The antibodies from the treatments simply could no longer recognize the virus’ new antigen structure.

Therefore, there is a dire need for the development of new, more specialized NAbs, that can recognize the newly mutated epitopes that are currently incompatible with current neutralizing antibody therapeutics.

Dr. Aaron LeBeau believes that key findings for creating more efficient NAb treatments could be derived from the likes of nurse sharks! Within the immune systems of sharks, antibody-like proteins called Variable New Antigen Receptors (VNARs) were found to be highly effective at neutralizing coronaviruses, according to his recent publication in the Nature Communications journal.

Due to the small and highly specialized structure, VNARs are able to access and bind to epitopes that human antibodies normally couldn’t. This superior ability allows VNARs to reach deep into pockets and grooves within the target antigen, allowing for a better fit and neutralization. Dr. LeBeau’s research team concluded that their data suggests that VNARs would be effective therapeutic agents against emerging SARS-CoV-2 mutants, such as the Delta and Omnicron variants.

With the help from researchers from the University of Minnesota and the Scottish biotech company, Elasmogen, the team hopes to develop the shark antibodies for therapeutic use within 10 years.

Do you think this is promising news? How do you feel about using shark “antibodies” in place of our own for serious cases of SARS-CoV-2? Assuming it’s safe, effective, and accessible to you, would you accept this treatment if you contracted a serious case of SARS-CoV-2? Please leave your thoughts in the comments.

Researchers Discover an Ancient Metabolic Process Ruled by the Concentration of Carbon Dioxide

By rileybosome

On January 17, 2022

In Student Post

Summary of the Krebs Cycle:

In AP Biology, we are currently learning about how the Krebs cycle (also known as the citric acid cycle) is one of the most important metabolic pathways for sustaining eukaryotic life and generating ATP.

In the matrix of the mitochondria, the citric acid cycle begins by the acetyl group from acetyl CoA attaching to an oxaloacetate molecule to form a citrate molecule. Citrate is then oxidized and in the process, releases two carbon dioxide molecules for each acetyl group used in the cycle. Three NAD+ molecules are converted to NADH, one FAD molecule is converted to FADH2, and a single ATP molecule is created. This pathway should occur a second time, as the oxidation of every two pyruvates creates two acetyl CoA, which begins the Krebs cycle.

The citric acid cycle also functions similarly in bacteria and eukaryotic systems, generally speaking.

There’s a “Reverse” to the Krebs Cycle Now?

In the absence of oxygen, some bacteria can perform the “reverse” of the Krebs cycle. This process results in the construction of biomass within bacteria that perform this process.

A key distinction between the citric acid cycle and the “reversed’ citric acid cycle, is that citrate synthase normally found in the Krebs cycle is replaced by ATP-citrate lyase in the “reversed” process. This is crucial because ATP-citrate lyase consumes ATP to split citrate instead of forming it. Another variation of this process requires no energy and has stumped researchers as to why organisms often utilize the energy costing pathway instead of the “easier” pathway to acquire biomass.

Researchers at the University of Münster decided to investigate potential factors that trigger this “easier” pathway in two kinds of anaerobic bacteria: Hippea maritima and Desulfurella acetivorans. These organisms thrive in oxygenless hot springs, with a carbon dioxide concentration of over 90 percent in their environment.

The team later found that the bacteria’s unique habitat proved to be an important factor responsible for the growth of the organisms’ biomass. After cultivating the bacteria under a diverse range of conditions, the research team discovered that the high concentration of carbon dioxide is responsible for enabling the “reversed” citric acid cycle in both anaerobic bacteria.

“It was mysterious why this ‘expensive’ version of the pathway exists if an energetically much cheaper alternative through the backwards reaction of citrate synthase is feasible. Now we know that this is due to the low carbon dioxide concentrations in many environments. The cheap alternative doesn’t work there.” researcher Wolfgang Eisenreich says.

What the Emphasis on the Concentration of Carbon Dioxide Means for this Pathway:

Carbon dioxide’s crucial role in this metabolic pathway suggests that it could stem from life on primordial earth. This is based on their theory that this “reversed” pathway was a widespread mechanism in organisms due to the surplus of carbon dioxide in the air during the primordial life timeline and the pathway’s unique dependence on high levels of carbon dioxide. Another supporting aspect to their theory is that 2.7 billion years ago, an estimated 25 to 50 percent of Earth’s atmosphere was comprised of carbon dioxide in contrast to today’s levels of carbon dioxide, which is about 0.04 percent.

The researchers have realized that the ATP-expending pathway exists due to the significant decrease of carbon dioxide in the air because the alternative pathway that doesn’t require energy isn’t possible without the surplus of carbon dioxide in the atmosphere.

Questions:

Do you believe they have truly discovered an ancient metabolic pathway? Or do you think these bacteria adapted to function this way?

Would you think that this process would be highly conserved in evolution if the carbon dioxide levels in the atmosphere didn’t dip?

Vitamin D Points to Potential Life-saving Therapeutics for Severe Cases of SARS-CoV-2

By rileybosome

On December 17, 2021

In Student Post

A promising new joint study by Purdue University and the National Institutes of Health (NIH) suggests that active metabolites of vitamin D are linked to reducing lung inflammation after SARS-COV2 infection. And no, before you break out your vitamin D pills, the vitamins inside your capsules are quite different from the active metabolites studied. Because of this, these researchers are warning those infected with COVID-19 against taking excessive supplements of vitamin D in hopes of reducing lung inflammation.

The researchers identified an autocrine loop involving vitamin D which allows T-helper (Type 1) cells to activate and respond to the active metabolites of Vitamin D which represses the signaling protein, Interferon Gamma. Distinguishing features of Interferon Gamma is the central role it plays in promoting inflammation.

Structure of interferon gamma. The two chains are colored in red (chain A) and green (chain B).

Although interferon gamma sounds wildly unrecognizable at first, we have actually learned about these proteins more broadly in our AP Biology class. Interferon Gamma is actually a type of cytokine! Regarding this cytokine’s structure, the proteins that compose interferon gamma are dimerized (sounds familiar? This is because we have also previously learned about dimerization through the tyrosine kinase receptor pathway in class!).

Along with the suppression of Interferon Gamma, Interleukin 10, a cytokine with potent anti-inflammatory properties, is amplified. This is significant because this cytokine prevents damage to the host and maintains normal tissue homeostasis by reducing inflammation.

Structure of interleukin 10 as published in the Protein Data Bank.

In the near future, these pathways could be exploited therapeutically to accelerate the shutdown program of hyper-inflammatory lung cells in patients with severe SARS-CoV-2 infections. But for now, before vitamin D is adopted to treat COVID-19, clinical trials are still needed. However, research findings like these are critical to creating effective treatment not just for those infected with SARS-CoV-2, but also other respiratory diseases as well.

What do you think about this new discovery? Do you think this could lead to scientific progress regarding the treatment of inflammation?

For Cancer Cells, it’s Halloween All Year Long– New Research Finds That They Masquerade as Normal Cells by Covering Themselves in “Sugary Costumes”

By rileybosome

On October 27, 2021

In Student Post

Dr. Rachel Willand-Charnley and her team of biochemist researchers at South Dakota State Univerity have achieved a “sweet victory” in cancer research. Their recent findings determine how cancer cells utilize sugar to deceive our immune systems. Their research suggests that cancerous cells mimic normal cells’ glycans due to genetic mutations, and because of this similarity, the immune system then confuses the cancer cell for a normal, healthy cell. This is because glycans on cell membranes of the cell are inspected by T-cells belonging to the immune system.

This is revolutionary to understanding the behavior and function of cancer cells which could help create more effective cancer treatments. Potential new treatment methods include stripping or altering the sugary layer of the cancer cell, allowing the immune system to recognize it as a threat and take care of it itself.

Milestones in cancer research are significant because as of right now, there is no cure for it. As we have learned in AP Biology, normal cells comply with signals that direct themselves into apoptosis, or programmed cell death. This process involves the expulsion of lysosomal enzymes into the cytosol which kills off the cell. This occurs when the cell is deemed inefficient or unable to function. If cancerous cells are detected by the immune system, those cells could avoid destruction by evading apoptosis signals and continue to progress within the human body which often leads to death.

How could a cancer cell bypass something like this? Well, it seems that their newly adapted sugary coating could play a role in avoiding those signals. This is because T-cells from the immune system inspect glycans in the extracellular matrix for deviations. When deviations are present, an immune response is triggered, which could also trigger apoptosis of the deviated cell. So, the modified glycans on the cancer cell’s extracellular matrix help cancer evade a process like apoptosis.

Isn’t it astonishing that a single genetic modification could actually make cancers resistant to immunotherapy and chemotherapeutics? What do you think about this discovery?

BioQuakes

AP Biology class blog for discussing current research in Biology

Author: rileybosome

Novel Nanobody Treatment Could be Used to Treat Animals Infected with SARS-CoV-2

How Gene-edited Strawberries are Safe and Beneficial to the Consumer

Could Sharks be the Solution to Ineffective SARS-CoV-2 Antibody Treatments?

Researchers Discover an Ancient Metabolic Process Ruled by the Concentration of Carbon Dioxide

Vitamin D Points to Potential Life-saving Therapeutics for Severe Cases of SARS-CoV-2

For Cancer Cells, it’s Halloween All Year Long– New Research Finds That They Masquerade as Normal Cells by Covering Themselves in “Sugary Costumes”

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