BioQuakes

AP Biology class blog for discussing current research in Biology

Author: quinniferous

CRISPR-Cas12a: The Next-Level Gene Editing Breakthrough

Did you ever wonder if gene editing was something from a science fiction film when you heard about CRISPR-Cas9? So grab a seat, because scientists at Yale are making fresh discoveries that will revolutionize gene editing technology! For many years, CRISPR-Cas9 allowed scientists to use a “guide” RNA to target and alter a single gene. That was amazing in and of itself, but now they have created a new set of mice models that can manage several genetic changes simultaneously. This means that researchers can continue to examine complex interactions in conditions like cancer and autoimmune diseases. 

File:CRISPR-Cas.svg
By Mariuswalter, translation by TheBartgry – GRNA-Cas9.svg, CC BY-SA 4.0, Link

The Yale team’s introduction of a next-generation technology called CRISPR-Cas12a, which can simultaneously target several genomic sites. This isn’t just advanced lab work; it’s a game-changer since it allows researchers to simultaneously fine-tune genes in different directions, similar to pressing several piano keys to produce a powerful chord. In simple terms, the project’s main researchers, Sidi Chen, Matthew B. Dong, and Xiaoyu Zhou, are promoting gene editing to investigate a variety of immune system responses. Now, we can acquire information on how particular changes affect immune cells in diseases including liver problems, skin cancer, and lung cancer. Furthermore, they can quickly create new disease models, which accelerates the development of treatments for a wide range of diseases.

Wait till you learn about the potential for the future if you think that’s incredible. These novel CRISPR-Cas12a mouse lines allow scientists to further studies on autoimmune illnesses, cancer, metabolic diseases, and even neurological conditions. With the help of the “molecular scissors” Cas9 and Cas12a, we can precisely cut, replace, or alter DNA, revealing details about how our bodies react to illness. These new discoveries are being used by Yale’s Systems Biology Institute and its Centers for Cancer, Stem Cell, and Biomedical Data Science to help develop medicines of the future. And it’s obvious that the world is keeping an eye on these innovative studies because they are supported by important organizations like the U.S. Department of Defense and the National Institutes of Health. Everyone is excited with the expectation that discoveries may occur quicker than in the past.

File:CRISPR-Cas9 mode of action.png
By ViktoriaAnselmOwn work, CC BY-SA 4.0, Link

A guide RNA follows the same base‑pairing rules learned in AP Bio: adenine pairs with thymine in DNA and with uracil in RNA, while cytosine pairs with guanine. Once the guide RNA locks onto its matching DNA sequence, the Cas enzyme acts like molecular scissors that let researchers remove, change, or swap genes, demonstrating how complementary strands are read and cut just as seen during DNA replication. After the cut, the cell’s transcription machinery copies the edited DNA into mRNA, and translation at the ribosome uses codons and tRNA anticodons to assemble new proteins, revealing in real time how a single nucleotide change can cause a point mutation, trigger a repair pathway, or alter gene regulation.

New Findings suggest Cancer Cure in the Near Future

Have you heard about King’s College London’s recent and fascinating discovery? It all comes down to BeeR, a unique bacterial protein that creates a stiff tube rather than a normal filament. To see exactly how BeeR functions, scientists used extremely sophisticated cryo-electron microscopes. To their surprise, they discovered a hollow cavity in the middle of this tube-like construction. That empty area is large enough to fit cancer-fighting medications, which is truly amazing. The researchers found that the BeeR protein may be built and destroyed at will utilizing ATP. This suggests that BeeR can transport medications directly to tumor locations, functioning as a miniature cargo box. It’s an ingenious approach that could revolutionize the way we treat cancer in the future. The idea that such a small protein could have such a significant impact is simply astounding!

 

Scientists realize that this discovery could lead to a medical revolution, despite the fact that the precise function of BeeR in bacteria is still unknown. To find out more about BeeR’s unique features, specialists from the University of Washington and King’s College London have been putting in endless effort. They think that by using this amazing bacterial protein, they might create more effective medicines for difficult illnesses like cancer. BeeR-based drug delivery devices are already being tested in breast cancer models by Prosemble, a spin-out business. If all goes according to plan, cancer medications may be administered to patients more efficiently than in the past. Imagine having the ability to keep medications inside BeeR and only release them where they are most required.  This finding serves as a reminder that sometimes the solutions to our most pressing health issues can be found in nature. All of the participants in this study have high hopes for the future. The road to beating cancer may be easier to see than we ever thought with BeeR!

Similar to the tubular structure of the BeeR protein, I studied how proteins fold and operate in my biology class. I discovered that ATP is the primary energy source for numerous biological functions, which is similar to how BeeR assembles and disassembles. We also looked at how signaling pathways help cells coordinate important processes like growth and division, which is directly related to the concept of more accurate cancer medication delivery. Everything I’ve learned about proteins, ATP, and cell-to-cell communication is brought together in a fascinating real-world example when I see BeeR in action.

File:EGFR signaling pathway.svg
By EGFR_signaling_pathway.png: Eikuchderivative work: Anassagora (talk) – EGFR_signaling_pathway.png, Public Domain, Link

Unraveling the Mystery of Cytokine Storms: New Insights into COVID-19’s Deadly Immune Response

Researchers from Johns Hopkins and other institutions discovered a new cause of “cytokine storm,” a dangerous immune response that can increase the risk of death in COVID-19 patients. Their findings were published in the Proceedings of the National Academy of Sciences on November 27, 2024.

Cytokines, as discussed in class, are small proteins released by macrophages that help control the immune system and fight infections.  A “cytokine storm”occurs when the body releases too many cytokines too quickly, leading to severe inflammation and damage to multiple organs.

File:Cytokine release following SARS-Cov-2 infection resulting in ARDS related to COVID-19.png
By Razaghi, Ali, Attila Szakos, Marwa Alouda, Béla Bozóky, Mikael Björnstedt, and Laszlo Szekely. 2022 – https://doi.org/10.3390/diagnostics12112789, CC BY-SA 4.0, Link

To find out what triggers cytokine storms, the researchers analyzed tissue samples from 40 patients who died of COVID-19. They looked at samples from various organs, including the lungs, heart, liver, kidneys, lymph nodes, and the nasal cavity.

They identified about 50 immune genes that were more active in the nasal swabs and continued to investigate these genes in the other tissues. Many of these genes are part of the “inflammasome,” a group of proteins that are a part of a signaling network that help the body fight off viruses and bacteria.

The researchers found that when these genes stay active instead of turning off, they can cause a cytokine storm.

In COVID-19 patients, immune genes in the nasal cavity (where the virus enters) send signals through a system called the renin-angiotensin-aldosterone system (RAAS) – this is a hormone system that usually helps regulate blood pressure, body fluids, and electrolytes.

In COVID-19, RAAS goes into overdrive, pushing the immune response into an overreaction. The belief is that this overreaction of RAAS may be responsible for causing the cytokine storm and preventing the inflammasome proteins to be turned off.  This impairs the infection-fighting function of the lymph nodes and severely damages the lungs, kidneys, heart, liver, and other organs. This may be the reason that some people were more likely to die from COVID-19.

Interestingly, the researchers believe that gene markers of this inflammatory response can be detected in the blood!  This can help identify patients at risk for severe COVID-19.  The researchers also believe their findings may help understand “long COVID,” a condition with lingering symptoms after the initial infection. This area remains a focus of ongoing research.

In biology, I have learned about cytokines, which are small proteins that help regulate the immune system and fight infections.  They are secreted by various cells, including immune cells like macrophages, B cells, and T cells. Cytokines help regulate immune responses by promoting or inhibiting inflammation, guiding immune cells to infection sites, and stimulating cell growth, differentiation, and repair.

This made me think of other components to getting infected with the virus.  For example, what other factors make you more susceptible to the body’s response to a covid 19 infection?  Does age play a role, other underlying health issues, or is it all written in our genes?

“DNA and miRNAs: The Universal Blueprint of Life – Uniting Unity, Diversity, and Genetic Regulation”

MicroRNAs (miRNAs) are a recent discovery that has revolutionized how we understand gene control. Imagine these tiny molecules, just 22 nucleotides long, as editors of our genetic script, deciding which genes get to speak and which stay silent. They do this by latching onto messenger RNA (mRNA)—the molecule that carries DNA’s instructions to make proteins—and either block its message or mark it for destruction. This process acts as a fine-tuned control system in our bodies, regulating essential functions and even playing a role in diseases like cancer.

The discovery of miRNAs came almost by accident in the early 1990s, thanks to two scientists, Victor Ambros and Gary Ruvkun. They were studying the roundworm Caenorhabditis elegans, focusing on a gene called lin-4 that, puzzlingly, didn’t seem to produce any protein. Instead, Ambros’s team found it produced a tiny RNA that bound to the mRNA of another gene, lin-14, blocking it from making protein. Around the same time, Ruvkun’s lab confirmed this connection, showing how lin-4 regulated lin-14 through this surprising, previously unknown mechanism. Initially, scientists thought miRNAs might be unique to worms, but as research progressed, they found these tiny regulators in many species, including humans. This was a huge revelation, showing that miRNAs are an ancient and crucial part of life’s genetic toolkit, silently shaping biology across countless forms of life.

Genetics laureatesThis discovery has led Victor Ambros and Gary Ruvkun to receiving the Nobel Prize in Medicine THIS MONTH (October 2024).  It has profound implications, as miRNAs are now known to be involved in various physiological processes and diseases, including cancer, offering potential new avenues for therapeutic intervention and advancing our grasp of genetic regulation mechanisms. miRNAs groundbreaking discovery in humans gives us limitless possibilities in what people could actually do. For instance, an ethical way to use miRNAs is to get rid of the part of the DNA that has the cancer in it to deactivate the cancer and turn it off. 

File:Conceptual overview of multiomics - digital skewed.png
By KajsaMollersenOwn work, CC BY-SA 4.0, Link

Learning about nucleic acids and gene expression is connecting everything we’re studying in AP Biology. DNA unites all living things with a shared genetic code, yet tiny changes in its sequences create the incredible diversity we see. As we dig into how genes work—turning DNA into RNA and then into proteins—it’s MIND BLOWING to see how DNA’s stability lets life continue, while its flexibility fuels evolution and diversity. Discovering microRNAs takes this even further, showing how even the smallest molecules can have huge effects on gene expression and open up possibilities for new treatments. This knowledge doesn’t just help us understand the unity and diversity of life; it gives us powerful tools to tackle big biological and medical challenges ahead.

I’m drawn to the study of biology, especially genetics, because it feels like the key to understanding life at the most fundamental level. The idea that tiny molecules like miRNAs can control complex processes and even influence diseases is fascinating to me. It’s incredible to think that such small miRNA can make such a significant impact on our health and development. The more I learn, the more I’m inspired by how understanding genes and molecular biology can unlock answers to pressing medical challenges and pave the way for new breakthroughs in medicine. This subject enhances my curiosity and makes me eager to contribute to a field with so much potential to change lives. How do you think that miRNA could change enhances in medicine, and what cures could we find with this breakthrough of miRNA?

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