BioQuakes

AP Biology class blog for discussing current research in Biology

Author: maragolgi

CRISPR: Revolutionizing Cancer Research and Treatment

CRISPR is a groundbreaking gene-editing tool that allows scientists to make highly specific changes to DNA. The system was originally discovered as a bacterial defense mechanism against viruses, where bacteria store fragments of viral DNA in special regions of their genome called CRISPR sequences. These fragments are used to create guide RNAs (gRNAs) that pair with a DNA-cutting enzyme called Cas9. When the same virus tries to attack again, the guide RNA matches with the viral DNA, and Cas9 cuts it, disabling the virus.CRISPR illustration gif animation 1

Scientists realized that this natural system could be repurposed in the lab to edit any gene by designing a custom guide RNA that leads Cas9 toa specific DNA sequence. Once the Cas9 enzyme cuts the DNA, the cell tries to repair the break. This repair process can introduce mutations that deactivate the gene, or scientists can insert a new piece of DNA to replace the original sequence. This makes CRISPR much faster, cheaper, and more precise than earlier gene-editing technologies like ZFNs and TALENs.

CRISPR is transforming cancer research by allowing scientists to study the function of individual genes involved in cancer. By using CRISPR to “knock out” or edit specific genes in cancer cells, researchers can see which genes are essential for tumor growth, metastasis, and drug resistance. For example, in the Cancer Dependency Map project, scientists used CRISPR to disable thousands of genes across hundreds of cancer cell lines. They identified over 600 genes that tumors depend on for survival—potential new targets for cancer drugs.

CRISPR is also used to create precise cancer models in cell cultures and animals by introducing mutations in oncogenes (genes that cause cancer when mutated) or disabling tumor suppressor genes (which normally prevent cancer). These models help researchers study how tumors develop and test potential treatments in a more controlled and accurate way.

In cancer treatment, CRISPR is being used experimentally to engineer patients’ immune cells to fight cancer more effectively. For instance, in clinical trials, scientists use CRISPR to modify T cells so they can better recognize and attack cancer cells. This includes deleting genes that suppress T cell function and inserting new genes that help them target tumor-specific antigens. One study modified T cells to recognize a protein called WT1, which is found in many tumors. These edited cells were then infused back into patients, showing early signs of safety and effectiveness.

This connects directly to what we learned in AP Biology, especially in our molecular genetics unit. We studied how DNA is transcribed into RNA and translated into proteins, and how mutations can affect gene expression. CRISPR works by directly targeting DNA to create those mutations or introduce new sequences, changing how genes are expressed. We also learned about bacterial immune responses and plasmid-based gene transfer—CRISPR was originally discovered as a prokaryotic immune system that captures viral DNA, and that same system is now one of the most powerful tools in modern medicine.

This topic is especially exciting to me because I want to go into cancer research and oncology. It’s incredible to see how a molecular system that bacteria use to fight viruses is now being used to fight cancer in humans. CRISPR allows researchers to explore the genetic roots of cancer and develop therapies that are personalized, precise, and potentially curative. Learning about how CRISPR works not just in theory but in actual clinical settings motivates me to be part of the next wave of scientists and doctors using genetics to save lives.

The Key to Finding Life on Mars: Microbes

Dvulgaris micrograph

The search for extraterrestrial life, particularly on Mars, has long been a driving force behind space exploration. Traditional approaches focus on detecting chemical biosignatures, potential byproducts of microbial metabolism such as organic molecules or atmospheric gases like methane, to infer the possibility of life. A recent study proposes a novel and potentially more definitive approach: detecting microbial motility. The ability of microorganisms to move, or “wiggle,” in a liquid environment could serve as a direct indicator of life, offering a promising alternative to conventional detection techniques.

Movement is a fundamental characteristic of many living organisms. On Earth, bacteria, archaea, and other microorganisms exhibit motility as a means of navigating their environment, seeking nutrients, and avoiding harmful conditions. Unlike chemical signatures, which may result from non-biological processes, microbial motion is an active behavior exclusive to living organisms. By focusing on motility, researchers aim to reduce false positives and establish a more definitive experiments for detecting life on Mars.

To investigate whether microbial motility could serve as a reliable indicator of life, researchers focused on three types of extremophiles: Bacillus subtilis, Pseudoalteromonas haloplanktis, and Haloferax volcanii. These organisms were chosen because they can survive extreme environmental conditions, making them strong comparisons for potential Martian microbes. The study aimed to determine whether these microbes would actively migrate toward a nutrient source in a detectable and repeatable way, a process known as chemotaxis.

The experiment involved placing microbe-packed water droplets on one side of a two-chambered microscopic slide, while an aqueous solution rich in L-serine—an amino acid essential for protein synthesis and cell proliferation—was placed on the other side. Over three-hour experimental runs, all three microbial species exhibited motility, swimming from their original location to form visible “blobs” in the chamber containing L-serine. This confirmed that the microbes could detect and move toward a favorable chemical gradient, demonstrating a clear and measurable response.

One of the primary advantages of this method is its specificity. While chemical biosignatures can sometimes be ambiguous, movement is an inherently biological trait, making motility-based detection a more reliable indicator of life. Additionally, this technique allows for real-time observation, enabling scientists to immediately assess microbial activity without extensive laboratory analysis. Another key benefit is that motility detection does not rely on active metabolism. Many microorganisms enter a dormant state when faced with harsh environmental conditions, making them difficult to detect through metabolic markers. However, if rehydrated in a liquid medium, dormant microbes may resume movement, making them easier to identify.

This method also provides a practical advantage for planetary exploration. Instead of continuously monitoring microbial movement, scientists can simply check whether microbes have migrated into a nutrient-filled chamber. This is particularly useful in extremely cold environments, such as those on Mars, where microbial movement may be slow. If alien microbes move at a much slower rate than those on Earth, future studies may need to extend observation periods from hours to weeks to detect motility effectively.

Despite its potential, implementing this method on Mars presents several challenges. First, collecting suitable samples is crucial. The Martian surface is exposed to intense radiation and extreme temperatures, making it unlikely to support active life. However, subsurface environments may provide more stable conditions, protecting microbes from harsh surface conditions. Thus, future missions would need to prioritize drilling into the Martian crust to obtain relevant samples.

Another challenge is the development of compact and reliable instruments capable of operating in Mars’ extreme conditions. These instruments must be durable enough to withstand the journey to Mars while maintaining the sensitivity required to detect microbial motion. Additionally, contamination control is essential to ensure that any detected movement originates from Martian microbes rather than Earth-based contaminants. Strict sterilization protocols and monitoring procedures would be necessary to maintain the integrity of the findings.

Furthermore, while L-serine was effective in prompting movement in Earth-based extremophiles, its is possible that extraterrestrial microbes won’t respond similarly. The challenge of determining what chemical attractants might be relevant to alien biochemistry remains an unanswered question in astrobiology. Future research will need to refine this method by testing different microbes and amino acids to ensure broader applicability.

This study connects incorporates knowledge from our Unit 1 study of prokaryotic cell structure, specifically on page 1 of Cell notes, where we discussed the role of  the flagella that enables movement in response to environmental stimuli. The ability of bacteria to move toward favorable conditions and away from harmful ones is an essential survival mechanism on Earth, and this same principle is being applied to the search for life on Mars.

As someone who grew up going to the planetarium at the Museum of Natural History in Manhattan, I used to sit in my seat wondering if the planets Neil Degrasse Tyson was commenting on had people like me. While it is very unlikely to find a life-form similar to our own on Mars, the thought of any life being there is fascinating. However, it is entirely possible that somewhere out in the vast expanses of the universe there are human-like beings. As technology advances and our knowledge of microbial motility expands, this research could bring humanity one step closer to discovering who and what else we share the cosmos with.

The Silent Pandemic: Long COVID’s Enduring Impact

SARS-CoV-2 without background

Since 2020, long COVID has emerged as a significant disability, impacting millions globally and incurring substantial economic costs. This article describes the intense research it has spurred has yielded over 24,000 scientific publications in just four years, marking it as one of the most intensely studied health conditions in recent history. Long COVID encompasses a range of long-term health effects following SARS-CoV-2 infection, from respiratory issues and debilitating fatigue to more severe conditions like heart failure and diabetes. Recent research has shed light on the mechanisms by which long COVID affects the body and the factors influencing its prevalence. 

A comprehensive report by the National Academies of Sciences, Engineering, and Medicine, commissioned by the Social Security Administration, further details the multifaceted nature of long COVID. It identifies over 200 potential health effects across various body systems, including cardiovascular, neurological, immunological, and metabolic issues. Neurological problems like cognitive impairment, strokes, and dysautonomia, along with post-exertional malaise, are particularly debilitating. The report emphasizes that long COVID can affect individuals of all ages, races, ethnicities, and baseline health statuses, with over 90% of cases stemming from mild initial infections. It also highlights the significant impact on individuals’ ability to work, attend school, and perform daily activities, often for extended periods. Notably, the report points out that current Social Security Administration disability criteria do not adequately capture some key long COVID symptoms, such as post-exertional malaise, chronic fatigue, and cognitive impairment.

Research indicates that health problems stemming from COVID-19 can persist for years. Studies have shown new health issues emerging even three years after mild infections, potentially linked to viral persistence in various organs and ongoing immune responses. Preliminary research also suggests a potential role of auto-antibodies in the development of long COVID symptoms, opening avenues for potential treatments targeting these abnormal immune responses.   

Despite the wealth of evidence regarding the risks of COVID-19 and long COVID, public messaging often downplays the continued threat. However, data indicates that COVID-19 infections still surpass flu cases in number, hospitalization rates, and mortality. Furthermore, COVID-19 leads to more severe and long-term health consequences. Equating COVID-19 with a common cold or the flu misrepresents the reality of its enduring impact on public health.

This ongoing research and understanding of long COVID is crucial for developing effective treatments and support systems for those affected, a cause I deeply care about due to its widespread impact on individuals’ lives and the global economy. As someone interested in public health solutions, I believe addressing long COVID is essential for mitigating its long-term societal consequences.

In conclusion, long COVID remains a significant public health challenge, requiring ongoing research, improved diagnostic and treatment strategies, and public awareness efforts to mitigate its widespread impact.

The New Annihilators of “Forever Chemicals”

Hafnia paralvei

Perfluoroalkyl and polyfluoroalkyl substances (PFASs ) unknowingly invade most aspects of our lives. From pizza boxes to sunscreen, PFASs are in many everyday products. However, the most common way PFASs enter our bodies is not through manufactured products but through water. Once PFASs enter the body, they can cause a plethora of health issues. U.S. scientists have found that these harmful compounds can lead to thyroid disease, high cholesterol, and kidney cancer. These “forever chemicals” earned their name due to their incredibly strong carbon-fluorine bonds, which make them very difficult to break.

Previously, the only way to break these seemingly indestructible bonds was by using extreme heat and pressure, which is neither convenient nor cost-effective. In this study, scientists screened the microbiome of wastewater, where they hit pay dirt. This is where PFAS-destroying bacteria enter the scene. Please welcome Acetobacterium, PFASs new nemesis. Scientists found that certain strains of Acetobacterium produce an enzyme that digests caffeate, a natural substance that closely resembles PFASs. Essentially, the bacteria break down PFASs by replacing the fluorine atoms with hydrogen atoms. Then, the fluorine waste is escorted out by transporter proteins. Over a three-week span, the bacteria broke down PFASs into smaller, more manageable fragments.

This process is related to how cells bring in foreign substances through endocytosis and use enzymes to break down the engulfed matter with lysosomes, as we learned on page 5 of the membrane notes and page 3 of the cell notes. This study combines our knowledge of membranes and cell organelles, showing how they work together to carry out cellular functions. In this case, the enzymes of the lysosomes of the bacteria break down the PFASs, which once broken down, the remaining fluorine is excreted via exocytosis.

Although this breakthrough discovery is a step in the right direction toward the eradication of PFASs in water, it is not perfect. These Acetobacterium strains only work on perfluoroalkyls with carbon-carbon double bonds, or “unsaturated” PFASs. Consider these the building blocks of larger PFASs. Scientists have also found a microbe, Acidimicrobium sp. strain A6, that can break down the two most numerous perfluoroalkyls. However, this microbe requires a lot of time to reproduce and needs very specific environmental conditions. Essentially, this method should only be used in combination with other methods, not by itself. The microbe-driven method of breaking down PFASs is still in its infancy, and hopefully, over time, scientists will find a way to break down larger PFASs in a timely and cost-effective manner.

In the meantime, a good way to limit PFASs in your water is by using a reverse osmosis filter. While it may not eliminate 100% of the PFASs, it is better than nothing. Until scientists discover a way to completely rid water of PFASs, be mindful of the water you are drinking—you don’t want PFASs invading your body!

As someone who has become increasingly aware and concerned with what enters my body, this topic resonates with me as bringing awareness to PFASs will not only alert people to be more careful, but possibly inspire more research to expedite the development of using bacteria to break down PFASs. I find it unbelievable that such harmful compounds are unavoidable in our every day life, and I am curious on how we can intentionally limit our exposure to PFASs. How do you think we can limit our exposure?

 

 

 

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