BioQuakes

AP Biology class blog for discussing current research in Biology

Author: cornophyll

CRISPR and the Battle Against Sickle Cell Anemia

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What is Sickle cell anemia, and why is its treatment so important?

Sickle cell anemia is a genetic blood disorder characterized by the presence of abnormal hemoglobin, the protein in red blood cells responsible for carrying oxygen throughout the body. In individuals with sickle cell anemia, the hemoglobin molecules are shaped like crescent moons, rather than the normal disc shape, giving them the name “sickle cell”. This abnormal shape causes the red blood cells to become rigid and sticky, leading to blockages in blood vessels and reduced oxygen flow to tissues and organs, as shown in the image above. As a result, individuals with sickle cell anemia experience episodes of intense pain, fatigue, jaundice, and susceptibility to infections. Sickle cell anemia is a lifelong condition with no cure, but various treatments exist.

What is CRISPR, and how can gene editing therapy help those with sickle cell anemia?

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CRISPR is a groundbreaking gene-editing tool that utilizes a naturally occurring bacterial defense mechanism, specifically Type-I CRISPR RNA-guided surveillance complex (shown above), which functions like molecular scissors, cutting DNA strands at precise locations. By incorporating a synthetic guide RNA that matches the target DNA sequence, scientists can direct the Cas protein to specific genes within a cell. Once bound to its target, Cas initiates a process that either disables the gene or introduces desired modifications.

In December of 2023, the FDA approved for this tool’s use in the treatment of sickle cell anemia. Dr. Stephan Grupp, chief of the cellular therapy and transplant section at Children’s Hospital of Philadelphia, explains the new treatment, stating that: “It is practically a miracle that this is even possible.” Developed by Vertex Pharmaceuticals and CRISPR Therapeutics, this therapy, known as Exa-cel or Casgevy, utilizes CRISPR technology to correct the genetic mutations underlying sickle cell anemia. Individuals like Haja Sandi, grappling with frequent and excruciating pain, view this transformative treatment as a beacon of hope. In her search for CRISPR treatment, Sandi told the New York Times, “God willing, I will go forward with it.”

However, the path to widespread implementation still faces many obstacles, including the complicated and costly procedures involved, limited availability at medical centers, and struggles in securing insurance coverage.

As the healthcare community navigates the logistical complexities of the treatment, the introduction of gene-editing technology marks a significant milestone in the ongoing battle against sickle cell anemia. Ultimately, this new treatment for sickle cell sets the stage for potential advancements in treating other genetic disorders, possibly leading us to a much brighter future.

What are your hopes and/or concerns regarding the future of gene editing and its potential impact on society? Comment below!

Summer Extends, Survival Narrows: Polar Bears and the Challenge of Longer Summers

Churchill, Manitoba draws around 530,000 tourists per year.

Churchill, an Arctic town in northern Manitoba, Canada, has long been famous for its polar bears. However, due to climate change, the polar bear population of the “Polar Bear Capital of the World”, has decreased, and will continue to dwindle.

One of the most well-studied effects of climate change has been longer summers, especially in the Arctic. Due to a phenomenon named arctic or polar amplification,    greenhouse amplification, from excessive production of CO2, will lead to increased temperatures near the poles, beyond the average of the planet. In the research of Rantanen et al, the team found that “During 1979–2021, major portions of the Arctic Ocean were warming at least four times as fast as the global average“. While there is no single cause of the phenomenon, one of the most frequently cited causes is the loss of sea ice. The loss of sea ice reduces the albedo, or ability to reflect heat rather than absorb it, as the dark ocean absorbs more heat than the reflective ice. The warmer temperatures will also prolong the period of ice melt, extending summers in the Arctic.

Located on the southern edge of Canada’s Arctic, Churchill, and the lives of its polar bear inhabitants have been severely altered due to the prolonged summers. Polar bear’s ideal food is the fat of seals, which provides them with the required energy to maintain their mass. However, they typically catch the seals best on ice, which can be hard to come across. While some believed that polar bears could harness the abilities of their relatives, the grizzly bear, Washington State University’s research on 20 different polar bears proved the notion far from the truth.

While some of the polar bears simply rested to conserve energy, in a similar fashion to hibernation, other bears actively searched for food. While some females spent as much as 40% of their time foraging, including a 175 km swim from one bear, their expenditure was simply not worth it. The bears could not eat their findings while swimming, nor bring them back to land. Because they had to travel so far, they had to spend even more energy than they would catching seals, while consuming far less energy.

A starving polar bear whose habitat is melting.

As the study shows, prolonged ice-free periods will increase starvation amongst polar bears, impacting the size of their population. During the study, the experienced weight loss, on average, was 2.2 pounds or 1 kilogram per day. In addition, when other researchers surveyed the polar bears in 2021, they “estimated there were 618 bears, compared to the 842 in 2016, when they were last surveyed.” It’s likely the bears had starved, as they are being forced onto land earlier, cutting into their typical period of gathering energy.

Remember, there are still ways we can help to combat climate change. You can reduce your carbon footprint by conserving energy at home, like turning off the lights when not in use. Using public transportation more often or switching to an electric car can reduce the CO2 emissions from your personal vehicle. Renewable energy, such as solar, is also effective in reducing our reliance on fossil fuels. Let’s take action today, and help make our planet more suitable for all of its inhabitants.

The “Slow but Steady” Increase of yet Another COVID-19 Variant: What are the Implications?

Globally, there has been a slow but steady increase in the proportion of BA.2.86 reported, with its global prevalence at 8.9% in epidemiological week 44” (WHO)

Another variant? Since the beginning of the epidemic, we have seen a few strains of COVID-19 arise, notably the Omicron, Delta, and Alpha variants. You may ask, how do these mutations keep on materializing?

Like all viruses, SARS-CoV-2 — the virus responsible for COVID-19 — goes under, and will continue to go under, several mutations.

File:SARS-CoV-2 without background.pngAs a coronavirus, SARS-CoV-2 uses protein spikes (visualization on right) that fit into cellular receptors, in order to infiltrate our cells. Upon entry of the virus, the invaded cell begins to translate the viral RNA into viral proteins, which leads to the production of new viral genomes. According to Akiko Awasaki, PhD, this is where mutations often arise, stating that, “When viruses enter the host cells and replicate and make copies of their genomes, they inevitably introduce some errors into the code.” While these introduced errors may be inconsequential, they can also be of benefit to the virus, increasing contagiousness. These successful mutations may change how the virus behaves in the future, becoming the foundations of new evolutionary steps.

As we learned in AP Bio, the sequence of amino acids plays a heavy role in the primary structure of the spike protein. When the sequence is altered, hydrogen bonds will be corrupted or created, affecting the stability of the secondary structures like alpha helices and beta pleated sheets. This changes will in turn affect the tertiary structure, ultimately morphing the three-dimensional shape of the spike protein.

Given this knowledge of how SARS-CoV-2 invades cells, and how it may lead to evolution and mutation, what is the significance of this newest variant, and how can it be fought?

BA.2.86 was discovered over the summer with cases from Denmark, Israel, the United Kingdom, and the United States. Later on, it spread to various countries all over the globe, being discovered in wastewater in countries such as Spain and Thailand. As weeks passed, the new strain did not seem to pose a threat compared to its predecessors. However, months later, BA.2.86 on the rise. On November 11th, the CDC estimated that 3.0% of cases came from BA.2.86. November 28th’s estimate, 8.9%, is shockingly almost triple of the earlier estimate just two weeks prior. This is apparently garnering the strain some sort of reputation, now being labelled a “variant of interest” by the World Health Organization.

While the percentage may seem scary, the rise of the strain has not brought a disproportionate growth in infections or hospitalizations. Rather than posing new or threatening danger, it seems to be much better adept to escaping our bodies’ defense systems. The improved ability to slip past antibodies, compared to previous variants, likely comes from its large number of mutations, 30, on its spike protein. Antibodies, which serve to fight these invaders, may find difficulty recognizing and defeating the new strain.

Due to the strain only taking the notice of researchers recently, there are still many things to be uncovered. Some researchers have affirmed their support in newer vaccines against BA.2.86 and future variants. As always, it is best to wear masks when necessary, wash your hands, quarantine if you are experiencing symptoms, and receive the latest vaccine.

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Breakthrough at MIT: Cutting and Replacing DNA Through Eukaryotes

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Scientists working at the Massachusetts Institute of Technology’s (MIT) McGovern Institute for Brain Research have found thousands of groundbreaking enzymes called Fanzors. Fanzors – produced in snails, amoeba, and algae – are RNA-guided enzymes. These enzymes combine enzymatic activity with programmable nucleic acid recognition, allowing a single protein or protein complex to aim at several sites. These enzymes were previously found in prokaryotes, like bacteria. 

An example of one of these enzymes is CRISPR, which instead of coming from Eukaryotes like the new Fanzors, CRISPR technology was adapted from the natural defense mechanisms of bacteria and archaea, a domain of relatively simple single-celled microorganisms”, according to LiveScience. Similar to Fanzors, these enzymes could alter genetic information and how the cell functions. 

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Orange ssDNA target bound to a type-I CRISPR RNA-guided surveillance complex (Cas, blue).

Although similar enzymes to Fanzors have existed, McGovern Fellow Jonathan Gootenberg says, “Eukaryotic systems are really just a whole new kind of playground to work in.” Eukaryotic cells carry membrane bound organelles, such as a nucleus, which holds genetic information, and a mitochondrion, which produces energy, but neither are found in prokaryotic cells, which have no membrane bound organelles. Eukaryotes are also the basis for both unicellular and multicellular organisms, while prokaryotic cells have no membrane bound organelles, and are solely the basis of unicellular organisms. Eukaryotes are found in animal cells, just like ours, while prokaryotic cells are found in bacteria and archaea. Furthermore, TechnologyNetwork says that prokaryotic cells are much smaller than eukaryotic cells “measuring around 0.1-5 μm in diameter”, while, “eukaryotic cells are large (around 10-100 μm) and complex”

Eukaryotic cell and its organelles (left) and a prokaryotic cell and its flagella, or tails (right) [NDLA]

As Gootenberg said, all these differences prove that a brand new pathway to further developments has been unlocked. Research has shown that these eukaryotic cells carrying the enzyme have developed the gene cutting enzyme over many years, separate from the development of bacterial enzymes. It is believed that this makes them far more efficient and precise than past enzymes. Fanzors are found to cut targeted DNA sequences with 10-20% efficiency, while other programmable RNA guided enzymes found trouble targeting a single sequence and often attacked others. Ultimately, this discovery is a major breakthrough and will lead to further developments in the process of cutting and replacing DNA. 

How do you expect or want this new discovery to be utilized? Are you excited for the  new avenues for research Fanzors can create? Let me know in the comments!

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