BioQuakes

AP Biology class blog for discussing current research in Biology

Author: cathoxylgroup

CRISPR: Zebrafish and gRNA

CRISPR-Cas9 is a revolutionary gene-editing technology, first invented by biochemist Jennifer Doudna and microbiologist Emmanuelle Charpentier. This method, aptly dubbed “genetic scissors,” enables scientists to cut DNA through precise removals and alterations of DNA sequences, which allows for the correction of genetic errors and the manipulation of gene expression. This technology has extreme potential to correct mistakes in DNA that cause conditions ranging from congenital birth defects and cancer. Additionally, CRISPR utilizes gRNAs (guide RNAs) to target specific sections of DNA/RNA in a cell. These gRNAs enable scientists to use CRISPR technology to cut genetic information with high precision.

Last month, researchers from Spain and the USA worked together to test how well modified CRISPR-RfxCas13d gRNAs could improve gene targeting in zebrafish embryos. They wanted to see how they could further improve CRISPR technology to target specific sequences in living organisms. They used chemically-modified gRNAs along with a protein called RfxCas13d to turn off genes active during the developmental stages in zebrafish embryos. They then modified the protein to be particularly efficient in zebrafish cells, and compared their various results of the CRISPR targeting.

Zebrafish (26436913602)

The scientists found that chemically-modified gRNAs do in fact improve the process of cutting out genetic information in living embryos. They further proposed that this process could be replicated to enhance the effectiveness of CRISPR editing in other organisms, too.

In this past AP Biology unit, we have learned about how harmful mutations can be, and what kinds of disorders can arise from those mutations. In class, we learned the different types of mutations (substitution, deletion, etc) and how even one seemingly small change in genetic code could have devastating effects on the affected organism; CRISPR might eventually be used to correct these harmful mutations in humans. Although there is still much more research to be done on CRISPR technology to reach the point at which we can begin to resolve genetic problems in humans, the possible uses of CRISPR are vast.

Whenever I think of CRISPR, I’m always reminded of the novel Brave New World, by Aldous Huxley. The book is set in a dystopian world where embryos are genetically modified to create people that “perfectly” fit their specific hierarchical positions and roles in society. As a result of gene editing, people in the depicted society lack true emotions and individuality. Although Huxley’s novel was written decades before CRISPR was invented, its warning about the dangers of manipulating genes rings true, especially now. What do you think of the ethical dilemma that CRISPR gene editing poses? How far is too far when it comes to scientific and technological progress, and who gets to decide those limitations?

Electrical activity spurs growth of small-cell lung cancer

Earlier this month, a team of scientists and researchers from across the United States, Taiwan, and the United Kingdom collaborated on a research study about the relationship between electrical activity and cancer. They explored how the neuroendocrine cells in small-cell lung cancer (SCLC) exhibit electrical excitability. In other words, cells that receive signals from the nervous system and respond by releasing hormones into the bloodstream, have demonstrated the ability to produce an electrical signal in response to a stimulus. The researchers ultimately found that electrical excitability plays a role in the growth of SCLC.

Neuroendocrine cells are similar to neurons in that both cell types are marked by calcium activity. The scientists tested whether the neuroendocrine cells in small-cell lung cancer would exhibit electrical excitability through the combined use of patch-clamp recording (a technique enabling researchers to measure current and voltages across a membrane through ion channels) and calcium imaging. They ultimately found that the non-neuroendocrine cells didn’t display electrical excitability, indicating that this signaling ability is only present in the neuroendocrine cells. Additionally, the researchers suggested that their finding of a significant increase in nerve fibers growing into early SCLC tumors indicates that the fibers form connections with cancer cells and interact with the cancer cells, similar to how nerves interact. Subsequently, the scientists proposed that electrical activity among neuroendocrine cells causes further development of SCLC.

Neuroendocrine cell hyperplasia

This study has given scientists potential avenues to finding new treatments for aggressive cancers like SCLC. The authors’ research, and studies similar to it, are crucial for developing a greater understanding of how cancer grows, and subsequently how to stop cancer from spreading.

Our most recent AP Bio unit on mitosis and genetics covered the topic of cancer as well. We learned that the cancer develops when a mutation in a cell bypasses checkpoints in the mitosis cycle, then begins to divide and grow. Additionally, we studied how mutations disrupt oncogenes, regulatory genes, and tumor suppressor gene, which ultimately results in cancer. SCLC, like other aggressive cancers, is typically caused by mutations in tumor-suppressor genes. While lung cancer and other aggressive cancers are notoriously difficult to treat, this study on electrical activity in cancer cells could hopefully lead to new treatment methods, as well as a deeper understanding of how cancer grows in the human body.

What do you think about the potential of studying electrical activity in cancer cells? Do you think it’s possible for scientists to develop new solutions based on the discovery of electrical activity in SCLC cells? I hope and believe that this research contributes to novel treatment methods for certain cancers.

Leaky Blood Vessels and Long COVID

Earlier this year, researchers in Dublin, Ireland, found that brain fog from long COVID is associated with blood-brain barrier disruption. COVID-19 is an infectious disease that causes symptoms lasting for two to six weeks, depending on the severity of the case. Long COVID, on the other hand, is a lingering illness that can cause one’s COVID symptoms to last for months. This lingering illness consists of prolonged COVID symptoms after initial infection, with patients reporting fatigue, dizziness, impaired taste and smell, and brain fog. Cognitive impairment, or brain fog, is a particularly devastating symptom of long COVID, as it causes the affected individual to experience mental exhaustion and forgetfulness. The team of researchers in the aforementioned article set out to find the root cause of brain fog in people with long COVID. They used dynamic contrast-enhanced MRI (DCE-MRI), which specifically measures tissue vascularity and permeability, to study patients’ brains. The researchers found that a significant percentage of long COVID patients who self-reported symptoms of brain fog also had increased blood-brain barrier permeability. The blood-brain barrier (BBB) is a protective layer that lines the brain’s blood vessels. In an earlier AP Bio unit, we learned that cell membranes are semi-permeable and filter out harmful substances. The function of the BBB is practically identical to that of a cell membrane: it is a semi-permeable bilayer that filters out harmful substances. Both the cell membrane and the BBB are structured with phospholipids, and both have transport mechanisms, include pumps, to filter substance in and out.

This research study ultimately suggests that long COVID disrupts the BBB and causes systemic inflammation. Systematic inflammation causes the body to experience irregular temperatures, increased heart and breathing rates, and produce an abnormally high amount of cytokines. This response ultimately leads to structural changes in the brain that cause brain fog. 

Novel Coronavirus SARS-CoV-2

While I don’t know of anyone in my personal life who has or had long COVID, I do know how awful it is to have regular COVID, so I can’t imagine how horrible it would feel for those symptoms to linger for months on end. Have you or someone you love ever experienced long COVID? What was it like for you or them to live with those symptoms?

Nanopillars and the Future of Nanomedicine

Earlier this month, researchers at the University of San Diego created nanopillars that give access to the nucleus without damaging the cell’s membrane. Currently, methods of accessing the nucleus for drug and gene delivery are invasive and therefore damage the rest of the cell. The key component of this non-disruptive method of accessing the nucleus is the nanoscale cylindrical structures (nanopillars). When a cell is placed on top of the nanopillars, the cell membrane curves and causes tiny openings to temporarily form in the nuclear membrane. The researchers verified their discovery by using their creation on cells with fluorescent dye in their nuclei. If the cells’ membranes were damaged through the use of nanopillars, the dye would’ve leaked out of the cells- but it didn’t. The nanopillars worked on skin cells, heart cells, fibroblasts (cells that contribute to the formation of connective tissue).

Nanopillars

I thought this article was interesting because my class focused on cell membranes throughout our first and second units of AP Biology. We learned about different types of membrane transport, specifically simple diffusion, facilitated diffusion, and active transport. Simple diffusion allows substances to enter a cell from a place of higher concentration, while facilitated diffusion uses channel and carrier proteins to allow molecules to move through a cell membrane. Active transport involves energy-fueled proteins that attach themselves to substances and transport these molecules across the membrane. I find nanopillars so interesting because unlike what we learned in class, these structures don’t rely on any type of membrane transport to insert substances into the cells- instead they provide a much more direct way for substances to enter the cell.

The potential of these nanopillars includes the potential to find innovative solutions and ways to treat cancer. They could be used to image a cancer cell, as well as tracking down the very presence of a cancer cell. Hopefully, if they are further developed, nanopillars can be used to deliver treatment directly to the nucleus of a cell, thus creating a more direct method of cancer treatment with less side effects than chemotherapy and radiation treatments. As someone who lost a relative to cancer, I really hope that this research will ultimately contribute to new cancer treatments, since this method enables the delivery of drugs to specific cells. What are your opinions on the potential of these nanopillars? Do you think researchers will be able to apply it in a clinical setting, or would it take a long time before we see such an innovation be used in medicine?

 

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