BioQuakes

AP Biology class blog for discussing current research in Biology

Author: atomicmass

CRISPR Gene Editing: The Key to Pharmaceutical Development

Sickle Cell Anemia

An article published in December of 2023 through ScienceNews identifies how the first CRISPR therapy approved in the U.S. will treat sickle cell disease. CRISPR therapy involves the process of changing the nucleotide sequence of a small segment of guide RNA in order to allow accurate targeting of almost any desired genomic locus for the purpose of correcting disease-causing mutations or silencing genes associated with disease onset (source). On December 8 of last year, the U.S. Food and Drug Administration approved gene editing, or CRISPR, therapy for use in patients ages 12 and older. The treatment, named Casgevy, is the worlds first treatment to alter cells using the Nobel Prize-winning molecular scissors. In addition, Lyfgenia, another gene therapy for sickle cell disease was approved on December 8. 

Previously, patients relied on drugs such as hydroxyurea or bone marrow transplants which didn’t always work for everyone. Casgevy on the other hand relies on a patients own cells. CRISPR treatment alters the genetic blueprint of bone marrow cells that give rise to blood cells in order to make new healthy cells. 

Approximately 100,000 people in the United States, most of them black or Latino, have sickle cell disease. Sickle cell disease is caused by a genetic defect in hemoglobin, the oxygen-carrying protein in red blood cells. While typical blood cell are flexible enough to slip through blood vessels, sickled blood cells are inflexible and often get stuck resulting in restrictions to blood flow and debilitating pain. People with severe forms of the disease may be hospitalized multiple times a year. 

Many scientists are excited about this new treatment option. Kerry Morrone, a pediatric hematologist at Albert Einstein College of Medicine in New York City says CRISPR-therapy treatment for sickle cell disease can give patients a “new lease on life” commenting on the fact that people with the disease often miss school, work, or special events due to the excruciating pain. 

Several clinical trials have tested the CRISPR based treatment Casgevy on participants. Victoria Gray, the first sickle cell patient to enroll in the trial recounted how the treatment changed her life. Gray had preciously described bouts of pain that felt like being struck by lightning and getting hit by a train at the same time. Now, pain-free, she is able to enjoy time with her family. Furthermore, Jimi Olaghere, another patient in the trial, told a similar tale. He says before treatment “sickle cell disease dominated every facet of my life” and “hospital admissions were so regular that they even had a bed reserved for me.” After the trial, he is pain free and able to present for his children while also doing the things he loves. 

Of course with any new discovery, there are challenges. Patients who wish to be treated with Casgevy must first receive chemotherapy to wipe out existing bone marrow cells so the new ones have a chance to thrive. Chemotherapy can raise the risk of blood cancer and cause infertility. It also kills immune cells which puts patients at higher risk of dying from infections. In addition, the therapy may cost up to $2 million per patient, but healthcare costs for sickle cell patients are already high over their lifetime. 

An article published the same day goes into more detail on how exactly this new treatment functions. The article states that the treatment also called exa-cel directs CRISPR to a gene, called BCL11A that typically prevents the body from making a form of hemoglobin found only in fetuses. The new therapy allows physicians to remove a person’s own bone marrow stem cells, edit them with exa-cel, destroy the rest of the person’s untreated bone marrow, and then re infuse the edited cells.  

A second article published in January of this year goes into detail about the CRISPR system itself and how it can be used to treat many different conditions. The article states that CRISPR gene editing unlocks the ability to precisely target and edit specific genetic mutations that drive the growth and spread of tumors as well as new possibilities for the development of more effective and personalized cancer treatments. CRISPR gene editing is not only useful for the treatment of sickle cell disease, but also useful in the treatment of a much wider scale. 

Similar to the methods in which CRISPR alters genes, in AP Biology class, we preformed a transformation lab in which we altered bacteria membranes through a heat shock in order to allow the plasmid, pGLO, to pass through the membrane and activate the gene for glow. CRISPR functions similarly to pGLO as they both are able to alter the genes inside of cells or bacteria in order to cure diseases or just make bacteria glow green as it did in AP Biology class. 

I hope this article helped simplify the ways in which CRISPR therapy works to treat sickle cell disease and other major diseases as well as explaining how this new discovery opens of many new possibilities in the world of medicine and pharmaceutical development. I look forward to seeing where CRISPR gene editing and therapy goes and how many diseases it will be able to cure in the future. What do you think?

Blueberries: Why They’re Blue

Blueberries-In-Pack

An article published on February 7th 2024 by ScienceNews identifies and reveals why blueberries are blue. Most people reading this article are probably wondering why this is such a big deal and how it relates to science. Spoiler, it does. The secret to a blueberries hue, or color, is in the structure of its wax coat. Many fruits such as grapes, plums, and blueberries have this waxy covering and researchers have identified that it is this waxy coat that makes these fruits appear blue to humans. 

Typically, blue is not a common color in nature and although there are some known blue fruits, few of them contain pigments of that shade. For example, blueberries contain large amounts of anthocyanin which is a skin pigment that should give each berry a dark red color, but structures in blueberries waxy outer layers work against anthocyanin creating their own blues. 

Rox Middleton, a physicist at the University of Bristol in England and Dresden University of Technology in Germany, conducted an experiment with the help of a few colleagues to better understand what is special about the berries waxy coverings. The group looked at a variety of fruits such as blueberries, Oregon grapes, and Plums under a scanning electron microscope to take a look at the finer details of blue-colored fruit skins. The resulting images revealed nano structures that reflect blue and ultraviolet light and cover up dark red anthocyanin pigments that are found underneath the waxy coating on blueberries skin. Furthermore, wax from the Oregon grapes became transparent when it was dissolved with chloroform

An article published on the same day through the University of Bristol provides another perspective on blueberries waxy coat. The article identifies that blueberries blue pigment can’t be extracted by squishing the berries because the pigment isn’t located in the juice that can be squeezed from the berry. The article then goes into further detail about the coating stating that it is an “ultra-thin colourant” around two microns thick that reflects UV light well which makes it appear blue as the coating is made up of miniature structures that scatter blue and UV light. 

A second article published by dole, helps explains the benefits of anthocyanin. The article states that anthocyanins bind to free radicals therefore protecting against some health disorders that can arise through oxidative processes such as cardiovascular disease and cancer. The pigment is also believed to have a positive effect on inflammation and high blood pressure as well as protecting the gut from bacteria by supporting the digestive system. 

To help further explain how pigments work and how we see certain colors, in AP Biology class, we learned that when a plant, for example, appears green, this is because that plant is absorbing all colors available except for green, which it reflects. This is why the rate of photosynthesis in plants is the worst in green light because the plant is unable to absorb the green light which contains the photons it requires to preform photosynthesis. Blueberries also reflect light, but it’s waxy coating instead reflects blue light which is why they appear blue to us. 

I believe that these new findings are very exciting as I personally didn’t realize that a waxy coating was responsible for blueberries blue appearance. I look forward to reading about more experiments like Middleton’s that help us further understand why certain fruits and vegetables appear the way they do, what do you think?

1.78 Billion Year Old Bacteria: the Origins of Photosynthesis

E. coli Bacteria (7316101966)

Pretty music everyone is aware of the term photosynthesis. We identify photosynthesis as the process plants take to make food by utilizing the sun’s energy. New findings take us back in time to the earliest signs of this process. The article published on January 3 2024 reveals that bacteria fossils hold some of the oldest signs of machinery required for photosynthesis. Cyanobacterias’s invention of photosynthesis is responsible for the oxygen in Earth’s atmosphere which is a large sum of information derived from fossils. 

The bacteria fossils are compression of carbon that don’t contain any mineralized structures such as bone or shells. The fossils also revealed that there are complex structures inside of the microscopic bacteria such as thylakoids which are located inside of the chloroplast and allow photosynthesis to take place. It is exciting to see such old thylakoids inside of the bacteria fossils but it is not unheard of as some researchers believe that thylakoids may have evolved before the Great Oxidation Event which occurred around 2.4 billion years ago and marked a significant increase in Earth’s oxygen levels.

During the period that the bacteria fossils lived in, oxygen levels in Earth’s atmosphere were at a fraction of today’s levels which helps explain why the fossils hint that there may have been small pockets where oxygen was abundant, possibly allowing the evolution of the ancestors of plants and animals. Most of the rocks that scientists believe may harbor fossils similar to the ones discovered have been compressed destroying intracellular structures like thylakoids which makes the findings even more rousing. 

A similar article published the following day identifies the bacteria fossils to be between 1.73 and 1.78 billion years old. Furthermore, the article points out that prior to this discovery, the presence of thylakoids in cyanobacteria was traced back to only around 600 million years ago, but now the earliest evidence of thylakoids in cyanobacteria is 1.2 billion years older. The fossils are also defined as Navifusa Majensis, a presumed type of cyanobacteria. N. majensis fossils add a vital data point in the timeline that aims to discover the exact timing of oxygenic photosynthesis’s evolution.

A second article published on the same day explains that the bacteria fossils “were laid down in mud and squeezed as the mud was transformed into shale over time.” The intriguing part, though, is that the internal structures of the cells were preserved throughout this process. 

To help further explain the job of thylakoids in plant cells, in AP Biology class, we learned about the specifics of the chloroplast, the organelle in plant cells that is responsible for photosynthesis and plants green color. Furthermore, we learned that grana, located below the inner membrane of the chloroplast, are stacks of thylakoids. A large surface area of thylakoid disks results in better productivity in the cell. In the article linked in the previous paragraph, astrobiologist Emmanuelle Javaux is referenced as speaking about “dark lines stacked through tiny sausage-shaped cells” that they believe represent thylakoids. An image in the Cells Notes Packet displays the same description that Javaux is providing with dark rectangles being spread across an image of the chloroplast. 

I believe that these new findings are a great advancement in the mystery that is the evolution of photosynthesis in plants. These findings are one of the first steps of discovering the exact timing of oxygenic photosynthesis’s evolution. I look forward to seeing if more fossils are discovered with thylakoids and other complex structures still intact, what do you think?

 

COVID-19: Multiple Doors and Multiple Species

An article published in August of this year identifies how the Coronavirus is able to jump from one species to another. Since the discovery of the COVID-19, the disease caused by the virus SARS-CoV-2, in 2019, many scientists have wondered how SARS-CoV-2 infiltrates cells by hijacking a protein called ACE2 which is found on human cells. At first, many believed that the ACE2 protein was required for infection, but recent discovery from the Virginia School of Medicine reveals that SARS-CoV-2 can use multiple pathways to enter cells. A good example to describe this discovery is a house. To the virus, ACE2 is the front door, but if the front door is blocked, the virus can use other proteins to enter the cells which can serve as a back door or windows in the “house.” This is concerning as SARS-CoV-2 is able to adapt to different proteins that serve as the doors into cells of other species. 

Coronavirus. SARS-CoV-2

After discovering that SARS-CoV-2 has the ability to enter cells using proteins other than ACE2, scientists conducted further research to determine the necessity of ACE2 in the infiltration fo healthy cells. As a result, it was revealed that SARS-CoV-2 can bind to and infect cells without ACE2 being present at all. You may be wondering what proteins besides ACE2 COVID-19 and SARS-CoV-2 use to enter and infect cells. Here is one example. 

An article published in the same month identifies TMPRSS2 as an endothelial cell surface protein that allows the spread of COVID-19 and SARS-CoV-2. The definition is similar to that of ACE2 as TMPRSS2 is simply another door or window that SARS-CoV-2 can use to enter healthy cells and infect them. TMPRSS2 is commonly found in the respiratory and digestive tracts which is a supporting factor to why the Coronavirus may encounter this protein. For example, someone infected with COVID-19 may sneeze near you resulting in you breathing the virus into your respiratory tract. 

In addition, an article published in the summer of 2022 explains an experiment done in order to determine the structure of the TMPRSS2 protein. The results section of the article confirms that TMPRSS2 is composed of three domains and three subdomains. An image of the protein shows tertiary protein structure surrounding the protein which is integrated into the membrane. The experiment allows us to see how similar TMPRSS2 is to ACE2 and how an antigen is able to bind to either protein and enter the membrane, but, how can this be prevented?

Although SARS-CoV-2 can enter cells in our body and infect them by entering protein channels such as ACE2 on the cell membrane, cells can create antibodies that attach to their cell membranes. In AP Bio class, we learned that in adaptive immunity, B-cell antibodies bind to foreign antigens while also inhibiting B cells to divide. B cells are then able to create B Memory Cells which recognize a foreign disease such as COVID-19 if it enters the body multiple times. B cells which are activated by B-Cell antigens, can protect our cells and prevent SARS-CoV-2 from infecting our cells by entering through ACE2 channels. 

I agree that these new findings have helped us understand how SARS-CoV-2 enter healthy cells allowing them to jump species, but I also believe there is more to discover about both of these diseases such as the question of whether or not a variant of SARS-CoV-2 can be created that is able to bi pass antibodies and enter cells at the same rate it would before vaccination or first infection. ACE2 and TMPRSS2 have been around for a while but we are just now discovering how proteins like them allow diseases to jump species. What do you think?

 

3300 Strains of Cells?

21 papers published on October 12th 2023, have revealed there is more to the brain than previously known. 3300 types of brain cells, a magnitude greater than previous reports, were discovered with the help of the Brain Atlas, a $375 million effort started in 2017. These new discoveries were made possible by new technologies that allowed scientists to probe millions of human brain cells with biopsied tissue or cadavers. This discovery is just the beginning, though, as these discoveries only sampled a small fraction of the 170 billion cells in the human brain. The process of obtaining the cells was lengthy and required several sources such as people who had recently passed away and those undergoing brain surgery.  Scientists attached glass tubes to each cell to inspect their electrical activity, injected dye to make their structure visible, then extracted the nuclei from the cells. Although this new discovery provides an astonishing amount of new data, the amount of cells discovered is only a fraction of the total number of cells within our brains so there could be up to 3300 more types of cells that we have yet to discover.

Mouse brain cells

An article published only two days after the one described above looks further into the 3300 cells types. The article identifies that the cells can be grouped into 461 clusters. In addition, new brain cells were found inside the cerebral cortex, the region of the brain responsible for memory, and language. Furthermore, an article published on the same day claims that neuron cells, responsible for transmitting stimuli, were present alongside the new cells in the samples they received. The article then identifies that from the cells obtained, half were neuronal cells and half were not.

Neurons, identified in half of the new cells, are the fundamental parts of the brain and nervous system. Our most recent topic in AP Biology is neurons and their functions. Neurons have many functions such as receiving sensory input from the external world, sending commands to the muscles, and transforming the electrical signals sent out during this process. The appearance of a neuron consists of three parts: dendrites, an axon, and a soma which can appear like a tree without leaves. Neurons are located all throughout the brain, with 10-20 billion in the cerebral cortex and 55-70 billion in the cerebellum (wikipedia) so it is not surprising that so many were identified in the new cells. Neuron cells are similar to eukaryotic cells in some ways, but not all. Like eukaryotes, they have a cell body that contains organelles. On the other hand, neurons have two branch structures, axons and dendrites, that differentiate them from a typical cell

Although the recent discovery of 3300 new types of brain cells is an astounding advancement in the ongoing research of the brain, this discovery is only a small portion of what lies within the large, independent system, that is our brain. How many cell varieties do you think are still undiscovered? I say hundreds.

 

 

 

 

 

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