BioQuakes

AP Biology class blog for discussing current research in Biology

Author: miachondria

CRISPR Reveals How mRNA Vaccines Work

Dr. KIM V. Narry led an important study on mRNA vaccines, like COVID-19, and how cells take them up and respond, as described in the article “Cellular regulator of mRNA vaccine revealed… offering new therapeutic options” from the Institute for Basic Science. This research explains how these vaccines enter cells, carry out their functions, and eventually get degraded. These new insights could lead to the development of better mRNA vaccines and treatments for diseases like cancer and genetic disorders.

In the study, over 19,000 genes were analyzed using a CRISPR-based screen, which led to the discovery of three key factors that affect mRNA vaccine effectiveness. First, the cell surface molecule heparan sulfate (HSPG) was found to help mRNA enter the cell. Second, a protein called V-ATPase was shown to release mRNA inside the cell by creating an acidic environment. Third, the protein TRIM25 acts like a security guard, detecting and destroying foreign mRNA.

The scientists found that proton ions, tiny charged particles, act as signals that tell the cell to launch a defense. When mRNA enters the cytosol, these ions alert TRIM25 to take action. This is the first evidence showing that proton ions can function as immune signals.

Cas9 in complex with sgRNA and target DNA

This article relates to what we’ve learned in AP Biology about protein synthesis and how mRNA is used by ribosomes to make proteins. The study shows that foreign mRNA must avoid being destroyed for this process to happen. TRIM25, part of the innate immune system (which we also studied this year), works to break down foreign RNA, but mRNA vaccines use a modified base (m1Ψ) to protect it and allow translation. This ties into what we’ve just learned about gene mutations. The discovery of proton ions also connects to our unit on cell communication, as it shows how cells respond to threats through chemical signaling.

I found this article fascinating as it included content from almost every unit we have learned this year! Let me know your thoughts in the comments. Did you know a single chemical change in mRNA could make or break a vaccine’s success? Do you think understanding our cells better be the key to curing diseases like cancer?

The Unexpected Side effect of CAR-T Therapy

There are many well-known side effects to cancer treatments, such as hair loss, nausea, pain, or fatigue. In rare cases, however, patients can experience a new side effect: a different cancer. The article “Rare side effects of cancer immunotherapy” by Anne Grimm of the Universität Leipzig discusses how new research shows that immunotherapy cancer treatments can trigger lymphoma to develop from modified T cells.

 As we learned in AP Bio and by the Cleveland Clinic, immunotherapy is a cancer treatment that utilizes your body’s immune system to detect and eliminate cancer cells. Your immune system recognizes and eliminates invaders, including malignant, cancerous cells. Similar to what we learned in class, the cells injected into the cancer patient undergo mitosis to rapidly divide for the patient to have as many cancer-killing cells in their body. Unlike these healthy cells, cancer cells are caused by uncontrolled mitosis, where cells divide uncontrollably due to mutations. While healthy cells go through checkpoints to ensure proper division, cancer cells bypass the checkpoints, allowing mutated cells to continue to divide.

The article describes a specific case where the genetically altered T cells in a 63-year-old patient developed T cell lymphoma following CAR-T treatment. According to the NIH (National Cancer Institute) CAR-T treatment is “A type of treatment in which a patient’s T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells.” Researchers discovered that the tumor was caused by the CAR-T cell alteration and underlying alterations in the patient’s hematopoietic stem cells. They examined signaling networks and genomic alterations using next-generation sequencing. 

Mitosis cycle

While these side effects only occur in around 1% of patients who undergo CAR-T treatment, researchers are studying similar cases to examine the risks of immunotherapy. The article ends by describing new studies being conducted by research to ensure the well-being of the patient’s health after receiving immunotherapy, as it is becoming a more common treatment for cancer. To stress the urgency of the research, the author describes how, to begin a study, researchers must typically wait several weeks or months for approval and publication. Consequently, this study was accepted after no longer than a day due to its importance.

When first learning about immunotherapy in AP Bio, I thought it sounded almost to good to be true. However, after reading this article, I discovered that in some rare cases, immunotherapy can do more harm than good. This leaves me with some questions: Do you think researchers should spend time and money studying something so rare? Could early screening methods help predict and prevent these rare complications before treatment begins?

 

Unpacking the Year-Round Spread of COVID-19

Have you ever noticed how COVID-19 cases continue to rise in the summer months? While most illnesses thrive throughout winter, COVID-19 has shown the ability to spike in cases year-round. The BBC article titled “Why COVID-19 is spreading this summer” by freelance science writer David Cox discusses how epidemiologists have observed a “summertime surge” in COVID-19 cases in the U.S. over the past four years. Despite their extremely hot summertime climates Arizona, California, Hawaii, and Nevada have seen increased cases and hospitalizations during the summer of 2023. Similarly, in Europe, where positive test rates climbed significantly this past summer. Researchers believe this phenomenon is largely driven by the emergence of FLiRT variants (a part of the newer omicron strand). The FLiRT variant has developed mutations in their spike protein, which allow them to bypass immune defenses- giving me my interest in the topic. As we recently learned in Bio, the mutations can evade barriers found in the innate immune system such as the inflammatory response, natural killer cells, and phagocytic cells.  What makes the virus so effective is that it attaches to human cells using the ACE2 receptor in the respiratory tract. As discussed in class, immunocompromised people have a difficult time for memory cells in response to the virus therefore it can often result in long-term COVID-19 or in rare cases death. While people have developed baseline immunity to older viruses such as RSV or the flu, COVID-19 is relatively new immunity, whether fromSARS-CoV-2 without background infection, or vaccination wanes more quickly. In addition, Cox discusses vaccination trends throughout the article. Although covid continues to be a threat throughout summer, people have stopped getting the vaccine as consistently as something like the flu.  Like discussed in AP bio, COVID-19 is crucial in building adaptive immunity which gives our cells immunological memory. Cox ends the article by discussing how COVID-19 will eventually settle into a more seasonal pattern, although this may take many years. However, these patterns that develop will be harder to read than those of the flu and RSV as the weather does not directly have an impact on the COVID-19 virus. The next question becomes- What does the future of COVID-19 look like as it transitions to a more seasonal virus? Will certain variants arise in certain seasons?

From Droplets to Life: How Water Chemistry and RNA Protocells Could Explain the Origins of Life?

How did the first cells come to be? How did life begin on earth?

These are two of the most common questions raised in the biology field. The main hypothesis regarding these questions is that simple molecules, or building blocks of life, enable the formation of cells. Molecular engineer Aman Agrawal describes his study in groundbreaking research on how RNA-rich protocells have formed over time in the research article, “Did the exposure of coacervate droplets to rain make them the first stable protocells?.” He describes how, because they allow vital biomolecules to be compartmentalized, protocells are necessary for life. RNA is thought to have been crucial in the early stages of life because it can store genetic information and catalyze reactions. The research article focuses on two other hypotheses. First, the RNA-world hypothesis states that RNA was the first molecule to form, making it the fuel for genetic material therefore allowing self-replication and evolution to take place. On the other hand, the coacervate hypothesis suggests that coacervates, droplets composed of molecular clusters that can concentrate essential components increase the rate of crucial metabolic processes needed for the origins of life. The coacervate hypothesis, which describes RNA exchange between droplets, emphasizes the importance of compartmentalization without lipid membranes, while the RNA-world hypothesis stresses the role of RNA. To confirm one of the hypotheses, Agrawal performed an experiment in which they mixed two materials, a negatively charged molecule, and a positively charged polymer, to create protocells. They combined to form tiny droplets known as coacervates. These droplets were unstable at first and merged quickly, causing their contents to mix. Researchers put in the distilled water to help stabilize them, creating a barrier around the droplets. It was found that whereas larger RNA pieces remained contained for days, smaller RNA pieces exchanged quickly between the droplets. This demonstrates that these droplets can maintain significant genetic material stable and apart, supporting the coacervate hypothesis and potentially providing an explanation for the origin of life. This article highlights what we have learned so far in AP bio considering it focuses on the chemistry of water as well as cell structure. More specifically, the article focuses on the importance of compartmentalization in protocells which directly correlates with the endomembrane system. The endomembrane’s main purpose is to partition the cell into compartments to carry out specialized reactions. This leaves the article parallel to the eWater Droplets ndosymbiotic theory. For me, I found this topic interesting when learning it in class ,however, after reading about this specific topics, I have gained a new apreciation for how this theory is applied to a specific biological discovery. While the article discusses the origins of protocells, the endosymbiotic theory focuses on the origins of specific organelles such as mitochondria and chloroplasts. Where they overlap is their use of membranes for cell function and compartmentalization. In addition, another important idea that relates to the article is the chemistry of water. Water has many unique properties, the most important being hydrogen bonding. Its ability to hydrogen bond creates a coating around it, ultimately helping to store genetic material. Water’s ability to maintain its structure allows it to act as a solvent in the experiment, ultimately allowing for the compartmentalization of RNA. One thing that caught my attention related to this article is that it doesn’t only give us insight to the burning questions of biology, but it can also be to discover origins of life elsewhere which has always been very interesting to me. How do you think these discoveries on water’s role in the formation of life might influence the search for life on other planets?

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