BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: Genes (Page 1 of 4)

Unlocking the Future: How CRISPR’s New Upgrade is Supercharging Gene Editing

Researchers at Yale University have developed a new approach using CRISPR-Cas12a technology to create advanced mouse models for studying genetic interactions that influence immune responses to diseases like cancer. This method allows scientists to simultaneously analyze multiple genes in a single experiment, making genetic research more efficient and insightful. 

File:CRISPR CAS9 technology.png - Wikimedia Commons

Over the past 15 years, advancements in the gene-editing technology CRISPR-Cas9 have provided significant insights into the roles specific genes play in various diseases. However, this technology, which uses a “guide” RNA, a small piece of RNA used in CRISPR gene editing to help scientists find the exact spot on the DNA they want to change, to modify DNA sequences and assess the outcomes, is currently limited to targeting, deleting, replacing, or modifying only single gene sequences at a time. 

 

However, the scientists have now created advanced mouse models using CRISPR  technology that enables them to simultaneously evaluate genetic interactions across various immunological responses to multiple diseases like cancer. Gene editing technologies enable scientists to use enzymes, such as Cas9, as molecular scissors to precisely cut or modify specific segments of DNA or RNA, providing valuable insights into the role of these genes in various disorders. The new tool, CRISPR-Cas12a, allows researchers to simultaneously evaluate the effects of multiple genetic changes that influence different immune system responses, according to the researchers.

 

The research noted this advancement could be valuable in the future to combat a host of pathologies, including cancer, metabolic disease, autoimmune disease, and neurological disorders.

 

This connects to AP Bio in multiple ways. For example, modifying genes can affect cellular functions and processes like cell division and apoptosis. This new technology is used to understand how changes in specific genes can influence cell behavior, which is essential in studying diseases like cancer. In addition, the new developments in CRISPR can be used to study impacts gene editing has on the immune system, and its various responses and functions throughout the body. Lastly, genetic mutation can be better understood through CRISPR editing as it effectively is creating its own “mutation”, changing sequences of codons to form different amino acids after DNA Replication, Transcription, and Translation. What are your thoughts on this research? How can it impact how we know genetics as we understand it today?

Exciting New Advancements in Gene-Editing Technology

In the past 15 years, advances in the gene-editing technology known as CRISPR-Cas9 has provided significant information about the roles that specific genes play in various diseases. However, as of March 25, 2025, this technology, which allows scientists to use a “guide” RNA to modify DNA sequences and analyze the effects, has only been able to delete, replace, target or modify only single gene sequences with a single “guide” RNA, limiting ability to evaluate multiple genetic changes at the same time. How interesting!

File:CRISPR CAS9 technology.png

Recently, however, Yale Scientists have created a series of high-level mouse models using CRISPR (“clustered regularly interspaced short palindromic repeats”) technology that permits them to simultaneously evaluate genetic interactions on a host of immunological responses to many diseases such as cancer. In general, gene editing technology allows scientists to implement enzymes, in this case, Cas9 (CRISPR-associated protein 9), as a “molecular scissors” that can accurately remove or modify sections of RNA or DNA, increasing understanding regarding the role these genes play in disorders. According to Sidi Chen, an associate professor of genetics and neurosurgery at Yale School of Medicine and a trailblazer in the field of CRISPR technology, the new tool, CRISPR-Cas12a, can aid researchers in simultaneously analyzing the effect of many genetic changes involved in multiple immune system responses. By using these new tools, Chen’s lab was able to induce and track modifications in many immune system cells in response to gene editing and was also able to tweak sets of genes in different directions simultaneously. Would you ever be interested in going into research similar to this study?

This article connects to AP Biology as it is related to gene expression and regulation which are essential to how organisms function. Even though all cells in an organism contain the same DNA, different cells express different genes depending on their role. Specifically, cells are able to regulate which genes are turned on and off and when that “turning on and off” happens. Regulations include epigenetic controls such as DNA methylation and DNA acetylation that affect the transcription stage of protein synthesis by influencing whether DNA is loosely or tightly wound. Tightly wound DNA (DNA methylation) works by turning off the genes in that region, while  loosely wound DNA (DNA acetylation) can be transcribed more easily. Once a gene is accessible, transcription factors such as enhancers influence whether a gene is transcribed. Following transcription, RNA processing occurs which includes RNA splicing which increases proteome diversity by removing the introns (non-coding regions) and keeping exons (coding regions) which form a mature mRNA molecule that is ready for translation. In this study particularly, researchers explore how gene networks interact to control expression patterns. As learned in AP Biology, changing one gene may have limited effects because of redundancy of others. However, by changing many genes in a system, researchers can observe how epistasis occurs (when one gene affects the expression of another). In AP Biology, we first learn about this regulatory complexity when learning about different operon models in prokaryotes (trp and lac), or the roles of enhancers, and transcription factors in eukaryotes. We study how one change in one part of the system can silence, activate, or modify other genes. By modifying genes involved in the immune response, the researchers in the study watch how the cellular regulatory system reacts or adapts. These reactions reveal how interconnected gene expression is, showing that genes operate as a part of a controlled system that determines the behavior of cells and ultimately a whole organism.

I found this article particularly interesting because it shows how often scientists are inventing new technologies and advancing every day- this article was written around just a week ago!

 

 

 

 

CRISPR Breakthrough: FDA Approves First Gene Therapy for Sickle Cell Disease

Gene editing just made history! The FDA just approved Casgevy, the first-ever CRISPR-based gene therapy for sickle cell disease. This is a massive step forward in genetic medicine and brings hope to thousands of people dealing with this painful and life-threatening disorder.

CRISPR logo

Sickle cell disease (SCD) is a genetic blood disorder that messes with hemoglobin, the protein responsible for carrying oxygen in red blood cells. Instead of being round and flexible, the cells become sickle-shaped and get stuck in blood vessels. This leads to extreme pain, organ damage, and a shorter lifespan. Until now, treatment options were pretty limited. The only real cure was a bone marrow transplant, but finding a matched donor is tough.

Sickle cell anemia

Casgevy changes the game by using CRISPR-Cas9 technology to edit a patient’s own bone marrow stem cells. Scientists take these cells, tweak them in a lab to boost fetal hemoglobin production (which helps prevent sickling), and then put them back into the patient. The result? Healthier red blood cells that drastically reduce pain and hospital visits.

This approval is huge for a few reasons. First, it’s basically a functional cure. Early trial results show that most patients treated with Casgevy are almost symptom-free afterward. Second, it removes the need for a donor, unlike traditional bone marrow transplants, which lowers the risk of rejection. And finally, it sets the stage for future CRISPR-based treatments for genetic diseases like cystic fibrosis and muscular dystrophy.

Even though this approval is a big deal, CRISPR research is still pushing forward. Scientists are working on making gene editing even safer and more precise. There are still ethical concerns, especially about who will have access to these treatments and what the long-term effects might be. But one thing is clear: this is just the beginning of a whole new era in medicine.

This connects directly to AP Bio’s Unit 6: Gene Expression and Regulation. In this unit, we learn how DNA controls protein production through processes like transcription and translation. CRISPR takes that concept to another level by directly editing DNA to change how genes are expressed. Understanding how this works gives us a deeper look at how cells function and how we might one day treat even more genetic diseases. The science we’re learning in class isn’t just theoretical—it’s shaping the future of medicine in real-time.

When I read about the FDA’s approval of Casgevy, the first CRISPR-based therapy for sickle cell disease, and it totally blew my mind! It’s amazing to think that gene editing can actually go into someone’s DNA, change it, and potentially cure a genetic disorder that’s been around for centuries. I always thought genetic diseases were something we just had to manage, but this shows that we might be able to change them at the molecular level. It’s honestly so cool to see science moving in this direction, where we can directly alter genetic codes to improve health outcomes.

It makes me wonder: Could we use this technology to treat other genetic diseases, even ones that are currently considered untreatable? And what could the long-term effects be of altering someone’s genes in such a precise way? Could this be a step toward eradicating certain genetic disorders entirely, or will there be challenges we haven’t even thought of yet? It’s exciting, but it also leaves me wondering what the ethical and practical limits might be for gene editing in humans.

What do you think—could CRISPR-based therapies like Casgevy eventually become a routine treatment for other genetic diseases, or do you think there are too many risks and ethical questions to consider before it becomes widely used?

Critter Chatter: Unraveling the Gene Behind Talking Animals

Consider a world in which humans could communicate with all animals and animals conversed with one another in the same way that we do. A universe in which mice have their own “language” secrets. Recent research into the NOVA1 gene reveals that such a world might not be as far-fetched as it sounds. Scientists discovered that a subtle change in NOVA1, occurring between 250,000 and 500,000 years ago, may have pushed our ancestors toward developing complex language. 

Mouse

In this study, researchers swapped the standard mouse version of NOVA1 with its human counterpart and found that the mice began producing more intricate and varied vocalizations. While the change wasn’t dramatic enough to give mice full linguistic abilities, it did alter their courtship “songs,” suggesting that even small genetic tweaks can influence vocal behavior. However, NOVA1 is far from the sole architect of human speech. Instead, it seems to be a single component among hundreds of genetic modifications that collectively laid the foundation for the evolution of language.

Alongside NOVA1, scientists have also examined FOXP2, another gene linked to speech and language development. FOXP2 has long been considered essential in speech because mutations in this gene can cause severe speech disorders in humans. When FOXP2 was introduced into mice in previous studies, researchers found that the animals also produced altered vocalizations, similar to the effects of NOVA1. Interestingly, while Neanderthals possessed the same FOXP2 variant as modern humans, they lacked the human-specific NOVA1 variant. This distinction suggests that the combination of different genes worked together over time to fine-tune vocal communication in Homo sapiens.

From an AP Biology perspective, this study clearly shows natural selection at work. Natural selection is when organisms with traits that enhance survival and reproduction become more likely to pass those traits on to future generations. The role of natural selection in genetic evolution highlights how small genetic changes, when beneficial, can become widespread and ultimately define the species. In the case of NOVA1, the human version of the gene provided a distinct advantage that was so significant that it quickly replaced its ancestral variant across nearly the entire human population. Out of over 650,000 individuals studied, only a handful still carry the original variant.

This research excites me because it poses great questions about how many “language genes” might have played a role and whether future studies might uncover even more about the complex interplay of genetic factors behind communication. It also makes me wonder if one day we could talk to animals.

What are your thoughts? Do you believe that such genetic tweaks could eventually lead to revolutionary changes in how we communicate? Let me know in the comments below!

 

Diving into the Sea of Gene Editing

Have you ever wondered why some people travel across the world just to go snorkeling or scuba diving? The answer is simple, Coral. Coral is one of the most beautiful organisms in the ocean. While coral is amazing, its looks are not all that it achieves. Coral is home to 25% of marine species while also feeding close to half a billion humans. Coral has such a huge impact on the world we live in, yet pollution and global warming are slowly taking out tons and tons of beautiful coral from our oceans. Although there are over 6,000 species of coral, we are going to narrow it down to just 1,500 and analyze the “stony corals” ability to build reef architectures.

Scleractinia (calcium skeleton of stony corals) at Göteborgs Naturhistoriska Museum 9006

Phillip Cleves is a scientist at Carnegie Melon who set out to use cutting-edge CRISPR/Cas9 genome editing tools to reveal a gene that’s critical to stony corals’ ability to build their reef architectures. Cleves highlights the ecological significance of coral reefs, emphasizing their decline due to human-induced factors like carbon pollution. Carbon emissions lead to ocean warming, causing fatal bleaching events, and ocean acidification, hindering reef growth. This acidification is particularly detrimental to stony corals, as it affects their ability to form skeletons made of calcium carbonate. Understanding the genetic basis of coral skeleton formation is a key research area to address this issue.

You may be wondering, what is CRISPR? CRISPR is like a genetic toolbox that scientists can use to edit DNA. Imagine DNA as a big instruction book that tells our bodies how to work. Sometimes, there are mistakes in the instructions, like a typo in a recipe. CRISPR lets scientists find and fix these mistakes. They can cut out the wrong parts of the DNA and put in the right ones, like editing a sentence in a book. This helps researchers study how genes work and could one day help treat diseases by fixing genetic errors. Using CRISPR, Cleves and his team were able to identify a particular gene called SLC4y which is required for young coral to begin building. The protein it encodes is responsible for transporting bicarbonate across cellular membranes. Interestingly, SLC4γ is only present in stony corals, but not in their non-skeleton-forming relatives. Together, these results imply that stony corals used the novel gene, SLC4γ, to evolve skeleton formation.

Finally, in AP Biology, you learn about genetics, the study of how traits are passed down from parents to offspring through DNA. CRISPR technology is like a super-advanced tool that geneticists use to manipulate DNA. It’s kind of like having a magic eraser for genetic mistakes! CRISPR also brings up the potential for gene editing in humans although sometimes it is seen as unethical. What genes would you edit if you had the chance?

 

The cause of Asymptomatic COVID-19 cases: A Gene Mutation

Novel Coronavirus SARS-CoV-2 (50047466123)

What is the cause of asymptomatic COVID-19 cases?

The study led by researchers at University of California San Francisco, published in Nature on July 19, 2023, provides the first evidence of a genetic basis for asymptomatic SARS-CoV-2 infection.  Individuals who contract COVID-19 but remain symptom-free are more than twice as likely to carry a specific gene variation. The genetic mutation, HLA-B15:01, common in about 10% of the study’s population, doesn’t prevent virus infection but remarkably prevents the development of symptoms. The research identifies the HLA-B15:01 variant as a key factor in solving the mystery of asymptomatic COVID-19 cases, with 20% of asymptomatic individuals carrying it compared to 9% with symptoms. The study, focusing on unvaccinated donors, finds that risk factors for severe COVID-19 don’t play a role in asymptomatic cases. The HLA-B*15:01 gene’s ability to recognize and respond to COVID-19, facilitated by T-cell memory, suggests potential targets for drug and vaccine development. The collaboration with La Trobe University delves into the concept of T-cell memory, highlighting the immune system’s ability to recognize SARS-CoV-2 due to exposure to similar peptides in seasonal coronaviruses. The research opens avenues for promoting immune protection against SARS-CoV-2 in future vaccine or drug development.

Recently in AP Biology, my class learned about the intricate mechanisms of the immune system.  This research directly connects to our learning of the immune system, more specifically memory cells which are highlighted in the article as a key piece of how the HLA-B15:01 gene functions.  T memory cells are cells which are responsible for recognizing and responding to all previous infections.  As previously mentioned, La Trobe University found that the HLA-B15:01 gene recognizes COVID-19 because of its similarity and to the more common coronaviruses people are regularly exposed to.  Once recognized the immune system has the capability to attack it with T-killer cells and potentially create and secrete antibodies through macrophages and plasma cells.

Since March 2020 I have been curious to the reasoning behind asymptomatic cases and I am happy to find a potential answer to this long unanswered question.  Why do you think this research has taken almost three years to find the answer to.  Comparatively, the COVID-19 vaccine was made in around 8 months from March of 2020. Of course there was significantly more incentive and money invested into the development of the vaccine, however the two findings are years apart and the vaccine is seemingly much harder to research and develop.

Sour Science!

Have you ever enjoyed an orange and wondered what causes its amazing citrus flavor? Well, scientists have recently discovered the origins of citrus’s sour taste. 

Scientists have recently discovered the origins of citrus fruits like oranges and lemons. In their study, they discovered a specific gene, PH4, that influences the fruits’ taste by regulating the fruits’ citric acid levels. Additionally, the researchers traced the fruits’ evolutionary journey from the Indian subcontinent to south-central China over millions of years and discussed influences that environments may have had on the citrus.

There are many reasons why these fruits evolved the way they did. One reason discussed in the article is human interference through selective breeding. Thousands of years ago, humans selectively bred certain types of citrus for food and medicinal purposes. Another reason they might have evolved to have more citric acid is to prevent bacterial infections. Bacteria, generally, prefer neutral environments with a pH of about 7. o.  Citric acid has a pH of about 3.2. Therefore, the more citric acid a fruit has the less likely bacteria can infect the fruit.

This relates to AP Bio through the involvement of genes in protein synthesis. During protein synthesis in a cell, the first thing that happens is transcription where information on the DNA is transcribed onto mRNA. The mRNA then is sent to the Rough Endoplasmic Reticulum where it is received on the cis face. There, on the ribosomes of the rough ER, the protein is synthesized. The type of protein that is synthesized here is determined by the information of the mRNA. Then the protein is sent to the Golgi where, based on the information from the mRNA, molecules are added to determine the final location of the protein. Genes, including PH4, are sections of DNA. Therefore, the PH4 gene, in part, determines what type of proteins are produced by the cell and where they go.

Wow! It is fascinating how a gene can influence an orange’s taste. I found this research so interesting because I love oranges. I wonder how other plants’ genes influence their taste?

Are Fish Mind Readers?

Several inherited behavioral mechanisms in humans and animals are deeply rooted in prehistoric animals. Some of these mechanisms, for example, fear, as well as the ability to fall in or out of love, humans have possessed for thousands of years and are found in our ancient genetic pathways. Although scientists are hesitant to attribute human-like feelings to animals, it has been proven that many animals, including fish, have moods. A recent study published in the journal; Science, demonstrated that fish can identify fear in other fish. This ability is regulated by the hormone oxytocin. This is the same “brain chemical” that controls the feeling of empathy in humans. The researchers discovered that fish could detect fear in other fish by deleting genes linked to producing and absorbing oxytocin. These fish became fearful as well.

Zebrafisch

Deleting genes involves various techniques, which is specific to the organism and the purpose for the deletion. Generally, there are two main approaches for deleting genes: Targeted Deletion and Random Deletion. In Targeted Deletion, very specific regions of the DNA sequence are removed or replaced to eliminate the gene of interest. Random Deletion occurs when large sections of the DNA sequence are randomly deleted in the hope of removing the gene of interest. The research focused on zebrafish brains; a small tropical fish often used for such research. The fish used in this experiment became practically antisocial and failed to change their behavior and could no longer detect when other fish were anxious. Scientists then injected oxytocin into some of the altered fish, and the fish’s ability to sense and react to the feelings of other fish was re-established. Fish behave just like humans in that they respond to other individuals being frightened. During this experiment, fish were seen paying considerably more attention to previously stressed or frightened fish.

Oxytocin is a hormone that plays a key role in social bonding and emotional communication in mammals, including humans. It is produced in the hypothalamus and released into the bloodstream by the pituitary gland. One of the primary functions of oxytocin is to produce social bonding between individuals. It has been shown to increase trust and cooperation between people, and it is often referred to as the love hormone because of its role in promoting feelings of love and intimacy.

Oxytocin with labels

Hans Hofmann, an evolutionary neuroscientist at the University of Texas at Austin, said that it’s less of a “love hormone” and more of a “scale” that helps fish recognize the most noticeable social situation. This recognition activates neural circuits that may make one run from danger or engage in behavior that results in mating. This ability is essential to certain species of fish survival.

Can Gene Editing Prevent Disease in the future?

There is very exciting news in the world of biology right now. For the first time ever, according to the University of California San Francisco‘s chancellor,  Sam Hawgood, CRISPR gene editing will be delivered to a human in an attempt to study how gene editing can help with asthma.

CRISPR-Cas9 Editing of the Genome (26453307604)

CRISPR-Cas 9 was adapted from a naturally occurring genome that allows bacteria to fight off viruses. When a bacteria was infected with a virus, it would use this genome to take pieces of the DNA from the virus and add them to its own DNA to create a pattern known as a ‘CRISPR array.’ The ‘CRISPR array’ allows the bacteria to remember the virus and cut the DNA of the virus apart.

In 2021, Peter Turnbaugh administered CRISPR into mice in order to target a specific gene and edit it out of the mouses gut. It was this work that inspired the scientists at UCSF to experiment with adding the CRISPR to a human microbiome.

Asthma is the perfect place to start because there is a clear microbial target to attack. There is a molecule that is produced by bacteria in the human gut that can trigger asthma in childhood. The scientists goal is to stop the microbes from producing that molecule, rather than remove the microbe altogether, as that microbe plays other beneficial roles in the human body. By taking a small piece of sgRNA, the scientists would be able to attach that to the target sequence in the DNA of the bacteria that produces that molecule, and ultimately stop the bacteria from producing the molecule that causes asthma.

This can be related to the topic of DNA and Genes that I learned about in AP bio. While reading the UCSF article, I couldn’t help but think about DNA replication, and what implications gene editing would have on DNA replication.

As we learned in AP bio, DNA replication is the process by which a cell copies its DNA before cell division, ensuring that each daughter cell receives a complete set of genetic instructions. During replication, the double-stranded DNA molecule is unwound and separated into two strands, each of which serves as a template for the synthesis of a new complementary strand. The result is two identical copies of the original DNA molecule.

If the scientists at UCSF were able to edit the genes to properly stop the microbes from producing the molecule that causes asthma, would that trait now be passed on to the new complementary strands? Would this gene editing get passed on through DNA replication, and even further would it be passed on to gametes? If both parents were to get this gene edited, would their zygotes now also be immune to asthma, and if so it is almost as if this gene editing is affecting natural selection and evolution.

All of this was very interesting to me and it seems that if/when this becomes a regular part of society, it will have major implications on the way our species sees diseases in the future.

If You Give A Mouse…Sight!

In a recent study published in the Journal Of Experimental Medicine, researchers in China successfully used CRISPR Gene-Editing technology to restore sight to mice with retinitis pigmentosa.

That’s a lot of vocabulary all at once, so let’s establish some definitions first and foremost.  According to the National Eye Institute, retinitis pigmentosa is a “genetic disease that people [and animals] are born with…that [affects] the retina (the light-sensitive layer of tissue in the back of the eye)”. As for CRISPR Gene-Editing technology, YG Topics defines it as, “a unique technology that enables geneticists and medical researchers to edit parts of the genome by removing, adding or altering sections of the DNA sequence”.

Most inherent forms of blindness and loss-of-vision stem from genetic mutations, and thus retinitis pigmentosa is one of many forms of genetically caused blindness.  However, through CRISPR technology, the researchers in the study successfully edited the DNA of mice who had the mutation to eliminate retinitis pigmentosa and give them the ability to see.  The results of the study are very promising, as not only does retinitis pigmentosa affect mice, but human beings.  Thus, there is evidence that CRISPR could be used to cure blindness among everyday people.  Kai Yao, a professor from the Wuhan University of Science and Technology who contributed to the study said, “The ability to edit the genome of neural retinal cells, particularly unhealthy or dying photoreceptors, would provide much more convincing evidence for the potential applications of these genome-editing tools in treating diseases such as retinitis pigmentosa”.

In AP Biology, we discussed how DNA factors into the traits of a living being.  DNA is made up of 3 base codons that form up to 20 different amino acids.  These amino acids code for specific proteins.  Through a process of DNA transcription and translation, the DNA uses various forms of RNA to code for proteins, which help tell the cell what to do.  Thus, the way the cell acts is largely determined by its DNA.  Essentially, DNA codes certain traits through various amino acid sequences.  Mutations and alternations to amino acid sequences cause different traits, such as red hair, blue eyes, or blindness.

Thus, successfully altering the DNA of mice has huge implications for the human race.  CRISPR could potentially be used to edit the DNA of humans, and thus help limit and prevent certain genetic conditions.  Many diseases are based on genetic mutations, and if CRISPR Gene Editing technology is proven successful, we could potentially eliminate genetic diseases in a few decades.  While “much work still needs to be done to establish both the safety and efficacy” of CRISPR technology, some groundbreaking scientific treatments could be coming sooner than you think (Neuroscience News).

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Is Nobel Prize-Winning CRISPR Technology as Sound as Scientists Say?

CRISPR—short for ‘clustered regularly interspaced short palindromic repeats’—is a nobel-prize winning scientific advancement in genetic modification technology. It was initially developed by Dr. Jennifer Doudna of Harvard University, and is based on the naturally occurring gene-editing system found in bacteria. Researchers now use this new method to modify the DNA of various organisms, potentially being able to make advancements in disease treatment, improving resilience of crops, correcting genetic defects, and more. 

CRISPR-Cas9 Editing of the Genome (26453307604)

To make an understatement, the introduction of CRISPR into the scientific community has been nothing short of groundbreaking, but researchers from Rice University have raised their own doubts about this seemingly miraculous technology, and whether or not it is as fool-proof as it’s presented to be. In response to this question, they have begun to lead an effort with a goal “to reveal potential threats to the efficacy and safety of therapies based on CRISPR-Cas9…even when it seems to be working as planned.” 

CRISPR-Cas9 was designed to treat sickle-cell anemia. In order to combat this disease, the technology works to edit large sequences in a patient’s DNA, therefore aiming to change their DNA and erase the aspect of it that makes them suffer from the illness. However, researchers have begun to fear that taking such a large step as this (erasing large portions of one’s DNA) is presumptuous, and could possibly yield dangerous, long-term effects, since this genetic modification CRISPR allows will only further spread throughout the patient’s body through stem cell division/differentiation. 

These fears mainly stem from the fact that scientists are not sure how DNA strands are able to rejoin after so many of their sequences have been cut out, and therefore, separated. However, bioengineer Gang Bao of Rice University has other concerns, as well: “large deletions (LDs) can reach to nearby genes and disrupt the expression of both the target gene and nearby genes.’”

Gene expression is a very complex process that occurs in the cells of all organisms, but which can be broken down into two major steps: transcription—”synthesis of RNA using information from DNA”—and translation—”synthesis of a polypeptide or protein using information in the mRNA.”  This process running smoothly is extremely important, as the ‘information from the DNA,’ or amino acid bases, need to be copied exactly without any mistakes, duplicates of bases, etc.. 

Bao also expresses another concern about CRISPR-Cas9: “‘you could also have proteins that misfold, or or proteins with an extra domain because of large insertions. All kinds of things could happen, and the cells could die or have abnormal functions.’”

With so many hypotheses at play, Bao and his research team knew they had to somehow figure out answers: they developed a technique called SMRT—’single molecule, real time’—that utilizes molecular identifiers to seek out and find accidental LDs, long insertions, and chromosomal rearrangements that are located at a Cas9 cutting site. To do this, a machine was used called the ‘LongAmp-seq’ (long-amplicon sequencing) to emphasize the presence of particular DNA molecules. This allows for the quantification of LDs and large insertions on a DNA strand. 

Researchers used streptococcus pyogenes as a medium. With this bacteria, they edited enhancers such as beta-globin (HBB), gamma-globin (HBG), and B-cell lymphoma/leukemia 11A (BCL11A), and genes such as PD-1 gene in T-cells of sickle-cell anemia patients. 

In testing these, they found incredible results: across the 3 enhancers and 1 T-cell gene, the average frequency of several thousand large DNA deletions averaged a whopping 20.025%. 

While it is unclear at this time whether Bao’s team’s discoveries will unveil consequences of genes modification by CRISPR technology, they state that they will work to “determine the biological consequences of gene modifications due to Cas9-induced double-strand breaks,” and look forward to testing if “‘these large deletions and insertions persist after the gene-edited HSPCs are [transplanted] into mice and patients.’

Are You Predisposed to Being Overweight? New Genetic Variations Say Yes.

Recent studies composed by researchers from the Spanish National Cancer Research Centre and the IMDEA Food Institute show that people with a specific variation or version of a gene crucial to cell nutrition tend to accumulate less fat. This means that those with a particular change or alteration in this gene may be inclined to store less fat in their bodies. Prior research has shown that genetics only play a role in 20% of our body weight for the general population. This means that other external factors such as diet, exercise, and overall lifestyle have much more of an impact on body weight.

Past research has identified nearly 100 genetic variants which slightly increase one’s likelihood of having a high BMI. This new research identifies one additional variant. Typically genetic variations are only slightly different versions of a gene and often do not result in visible changes. But, this new variation challenges this idea. It affects the amount of fat the body stores, something which can strongly alter one’s physical appearance. What’s more, the researchers of this gene have found that it is more prevalent in Europe with just under 60% of the population having it.

Ácido desoxirribonucleico (DNA)

 

According to Alejo Efeyan, the head of CNIO’s Metabolism and Cell Signalling Group, the new research can help us to further understand the role which genes play in obesity, body weight, and fat accumulation. Efeyan says, “the finding is a step forward in the understanding of the genetic components of obesity.” Additionally, Ana Ramirez de Molina, the director of the IMDEA Food Institute, claims that a key understanding of cell pathways regarding cell nutrition may affect and spur the creation of not only obesity prevention but also personalized treatments. Essentially, understanding the new gene can help us to target obesity and body weight on an individual level rather than the population as a whole. She believes, “a deep knowledge of the involvement of the cellular nutrient-sensing pathway in obesity may have implications for the development and application of personalized strategies in the prevention and treatment of obesity.”

To find and research the genetic variant which influences fat storage and obesity a team from the IMDEA Food institute collected a variety of data from 790 healthy volunteers. This included body weight, muscle mass, genetic material, and more. The researchers found a “significant correlation between one of these variants in the FNIP2 gene and many of these obesity-related parameters.” Essentially their research proved that there is a connection between the specific gene and factors of obesity. The study has also been published in the scientific journal of Genome Biology. Although this gene may play a role in keeping body fat storage lower than others, it is important to note that it is not entirely a preventative measure against obesity or fat gain. Efeyan clarifies, “It is not at all the case that people with this genetic variant can overeat without getting fat.”

The genetic variation is present in a gene that specifically partakes in a signaling pathway that tells the cell what nutrients are available and needed. The gene signals to the cell what nutrition is necessary at a given moment. In our AP Bio class, we learned the intricacies of cell communication; how and why it can occur, the stages of it, and even the differences in the distances of communication. Connecting back to our AP Bio class, I wonder whether the gene interacts in an adjacent, paracrine, or long-distance manner. Also, how the distance can affect the communication of the gene to the cell regarding cell nutrition. We also learned about how genes in the nucleus of our cells can code for specific factors in our bodies and how they are a sort of ‘instructions’ for us to carry out. This connects to the research as we can see that a change in a gene can alter our body’s fat storage and connection to obesity. The genetic variation changed the ‘instructions’ for weight, fat storage, and obesity disposition. Additionally, the research stated that 60% percent of Europeans have genetic variation, I wonder what may have caused this. Was it a result of their diets, lineage, geography, or just a scientific anomaly? I invite any and all comments with a perspective and an idea as to what may have caused this, along with any comments regarding this research as a whole.

Obesity-waist circumference

 

 

Would You Have Survived the Black Death?!?!

New research from McMaster University, the University of Chicago, the Pasteur Institute, and other organizations suggests that during the Black Death, 700 years ago, there were select individuals whose genes actually PROTECTED them from the devastating population-crushing Bubonic Plague.

Model of bubonic plague bacteria - Smithsonian Museum of Natural History - 2012-05-17

The Bubonic Plague, later nicknamed the Black Death after many realised people would develop blackened tissue on their body postmortem, due gangrene(the death of tissue due to lack of blood flow). “It remains the single greatest human mortality event in recorded history, killing upwards of 50 per cent of the people in what were then some of the most densely populated parts of the world.” (ScienceDaily.com)

The team researching this genetic phenomena collected DNA from the deceased 100 years before, during and after the Black Death. They collected samples from the greater London area, as well as some parts of Denmark to accurately represent Upon searching for evidence of genetic adaptation, they found 4 different genes prevalent in the pandemic survivors, all of which are protein-making genes that are used in our immune systems, and found that versions of those genes, called alleles, either protected or rendered one susceptible to plague. We in AP Biology will soon learn more about alleles in higher depth, for they are imperative in the genetics of almost every DNA-carrying organism’s survival.

People with two identical copies of a gene named ERAP2 were able to survive the Black Plague at significantly higher rates than those who lacked that specific gene. “When a pandemic of this nature …  occurs, there is bound to be selection for protective alleles in humans … Even a slight advantage means the difference between surviving or passing. Of course, those survivors who are of breeding age will pass on their genes”.- evolutionary geneticist Hendrik Poinar. Mr. Poinar’s analysis of this research poses a unique and interesting question. Does the natural selection that occurred during the Bubonic Plague mean that you and I have a higher chance of having this gene in our DNA? If another plague with a similar biological makeup to the Black Death, would our bodies be better suited to find it?

Can CRISPR Gene Editing Cause Problems in the Embryos it is Meant to Customize?

Researchers from around the Tri-State area came together in 2020 to examine the effectiveness of the Crispr-Cas9 double stranded DNA break (DSB) induction on human embryos to repair a chromosomal mutation. The study, which was published in Cell, began with sperm from a mutated male patient at the EYS locus, which causes retinitis pigmentosa blindness. The researchers then attempted to use CRISPR-Cas9 technology to repair the blindness gene in a number of fertilized embryonic stem cells that carried the EYS mutation.  The results showed that about half of the breaks in the experiment went unrepaired, which resulted in an undetectable paternal allele. After mitosis, the loss of one or both the chromosomal arms was also common. This study shows that using CRISPR-Cas9 technology is still in its early days, and needs to be further vetted before it is used to treat patients.

CRISPR Cas9 technology

Instead of correctly and consistently editing the genome of the embryos, the Crispr-Cas9 wreaked havoc, leaving behind chromosomal trauma. The data shows that the embryos started to tear apart and get rid of big pieces of the chromosome that had the EYS mutation, some losing the entire chromosome. The promise of Crispr technology is about changing one gene, but how can that be done when a larger, untargeted part of the genome is also being altered? Dr. Egli, the paper’s main author, brought up a more likely use for the Crispr editing: deploying it as a form of “moleculure bomb”, sent in to shred unwanted chromosomes. An important part of using gene editing is the ability to consistently predict the outcome, However, the resulting “mosaicism prevents inferring the genotype of the fetus from a biopsy and is thus incompatible for clinical use”, according to the Cell authors.

There were many rarities that appeared in the alleles of the embryos used. With a small sample size, due to the difficulty to acquire human embryos, there was no ability to rule out rare events. Although there were combinations of maternal and paternal alleles that showed interhomolog events, they occurred after the two-cell-stage injections, all mosaic. A single Cas9-induced break can result in outcomes in the human embryo that suggest species-specific differences in repair. In on-target sequencing of the cells, the detection of only a wild-type maternal allele might have been because of the unrepaired breaks and the loss of the chromosomal arm or the loss of the entire chromosome. This study shines light on the dangers of Crispr gene editing. The quotes from researchers, doctors, and genealogists all echo the same risk, we must walk before we can run. Testing and ensuring the safety of using Crispr on an embryo before the first round of DNA replication happens is crucial to the ultimate promise of gene repair. If it can’t be done safely with no off target effects, then Crispr “would be deeply unethical”, according to Dr Faraheny from Duke University.

Can Cancer Cell’s Medication Immunity Be Stripped?

Cancer is one of the hardest diseased to fight. If a tumor begins to grow inside of a patient, they may be given drugs to fight off the corrupt cells. The problem with this is that the cancer cells could become immune to these drugs. Through the use of CRISPR. In Novel Crispr imaging technology reveals genes controlling tumor immunity, a new way of fighting cancer is revealed. Instead of targeting the whole tumor, Perturb-map marks cancer cells and the cells around cancer cells. Once this is completed, it is able to identify genes controlling cancer’s ability to become immune to certain drugs.

Mitosis appearances in breast cancer

To fight cancer cells, scientists use thousands of CRISPRs at the same time. This identifies every gene in a sequence and allows them to be studied. Through Perturb-map, scientists can now dive deeper and find where the cell immunity to drugs originates. A certain pathway in the cell is controlled by the cytokine interferon gamma or IFNg, and a second is by the tumor growth factor-beta receptor or TGFbR. When the cell had a gene with TGFbR2 or SOCS1, the latter of which regulates IFNg, tumor cells grew. When the cell lacked one of these, it shrunk. Moreover, it was discovered that tumors with SOCS1 were susceptible to attacks by T cells, but TGFbR cells had immunity against them. This stayed true even when both types of cells lived in the same environment. With findings like these emerging more and more, the future of cancer treatment is looking brighter than ever.

Chromosome DNA Gene unannotated

Could Overproducing A Gene Prevent Parkinson’s Disease?

A team from the University of Geneva (UNIGE) discovered a gene that, when overexpressed, prevents the development of Parkinson’s disease in fruit flies and mice. Parkinson’s disease is a movement disorder caused by a brain disorder. Parkinson’s disease symptoms typically appear gradually and worsen over time. Men are affected by the disease at a rate that is roughly half that of women. A combination of genetic and environmental factors contributes to the disease’s underlying cause.

Emi Nagoshi, Professor in the Department of Genetics and Evolution at the UNIGE Faculty of Science, studies the mechanisms of dopaminergic neuron degeneration using the fruit fly. The midbrain dopaminergic neurons are the primary source of dopamine in the central nervous system. Their absence is linked to Parkinson’s disease. Emi’s test connects to the Fer2 gene, whose human homolog encodes a protein that regulates the expression of many other genes and whose mutation may lead to Parkinson’s disease through unknown mechanisms. 

The absence of Fer2 causes Parkinson’s disease-like symptoms, the researchers investigated whether increasing the amount of Fer2 in the cells could provide protection. When flies are exposed to free radicals in their environment, such as toxins, their cells undergo oxidative stress, which leads to the degradation of dopaminergic neurons. By creating mutants of the Fer2 Homolog in mouse dopaminergic neurons, the scientists were able to show that oxidative stress has no negative effect on the flies if they overproduce Fer2, confirming the hypothesis of its protective role. They discovered abnormalities of these neurons, as well as defects in movement patterns in aged mice, just as they did in the flies.

Alleles on gene

Genes can have alleles, which give different traits to different people.

In comparison with our unit, the Fer2 provides the understanding of how the molecules that make up cells determine the behavior of in this case mice and fruit flies. Each is made up of nucleotides that are arranged in a linear fashion that resides in a specific location on a chromosome. Most genes encode for a specific protein or protein segment that results in a specific characteristic or function, such as providing a protective barrier towards Parkinson’s disease.

 

 

 

Instead of Bringing Back Dinosaurs, These Scientists are Bringing Back the Extinct Christmas Island Rat

Majestic dinosaurs and mammoths on our planet both underwent extinction millions and millions of years ago. The Christmas Island rat? In 1908. De-extinction techniques, also known as resurrection biology, garnered popularity within the science world in the 1990s. The Encyclopedia Britannica defines it as, “the process of resurrecting species that have died out or gone extinct.” Here is how these scientists are attempting to bring back a rat species that you have probably never heard of, and what that can mean for the future.

De-extinction using CRISPR gene-editing

 

File:MaclearsRat-PLoSOne.png - Wikimedia Commons

path of extinction of the Christmas Island rat

The process of de-extinction with the Christmas Island rat is driven by the method of CRISPR gene-editing, which allows for the genome of organisms to be modified, or edited, meaning that an organism’s DNA can be changed by us humans. This allows for genetic material to be added, removed, or modified at specific locations said genome. The idea behind the de-extinction of an animal through CRISPR gene-editing is to take surviving DNA of an extinct species and compare it to the genome of a closely-related modern species, then use CRISPR to edit the modern species’ genome in the places where it differs from the extinct one. The edited cells can then be used to create an embryo implanted in a surrogate host.

CRISPR thought to be “genetic scissors”

Thomas Gilbert, one of the scientists on the team of this project, says old DNA is like a “book that has gone through a shredder”, while the genome of a modern species is like an intact “reference book” that can be used to piece together the fragments of its degraded counterpart.

What is the difference between a genome and a gene?

File:Human genome to genes.png

Gene depicted within genome

Genes, a word you are most likely familiar with, carry the information which determines our traits, or features/characteristics that are passed on to us from our parents. Like chromosomes, genes come in pairs. Each of your parents has two alleles of each of their genes, and each parent passes along just one to make up the genes you have. Genes that are passed on to you determine many of your traits, such as your hair color and skin color. Known dominant traits are dark hair and brown eyes, while known recessive traits are blonde hair and blue or green eyes. If the two alleles that you receive from your parents are the same, you are homozygous for that gene. If the alleles are different, you are heterozygous, but you only express the dominant gene.

Each cell in the human body contains about 25,000 to 35,000 genes, and genes exist in animals and plants as well. Each gene is a small section of DNA within our genomes. That is the link between them, and they are not the same.

Is this possible? Can we really bring back the dead?

Reconstructed image of the extinct woolly mammoth

See, CRISPR gene-editing itself is of great interest for having shown promising results in terms of human disease prevention and treatment for diseases and single-gene disorders such as cystic fibrosishemophilia, and sickle cell disease, and shows promise for more complicated illnesses such as cancer, HIV infection, and mental illness–not so much with de-extinction. Here’s a simple diagram displaying the process.

File:Crispr.png

In this scenario, it is not looking very likely that these rats can come back. Gilbert and his team of 11 other scientists, through extensive processes and attention to small-detail, have in total reconstructed 95% of the Christmas Island rat genome. While 95% may be an A on a test, in regards to genomes, that 5% is crucial. In this case, the missing 5% is linked to the control of smell and immunity, meaning that if we were to bring this animal back, it would lose key functionality. Gilbert says 100% accuracy in genome reconstructing of this species is “never” going to happen.

The success of de-extinction is quite controversial in itself. Restoring extinct species can mean an increase in biodiversity and helping out our ecosystems which are suffering greatly from climate change.  However, research also suggests it can result in biodiversity loss through possibly creating invasive species (yes, I wrote this) or for other reasons.

While the science is interesting, the reality of the unlikeliness of de-extinction becoming a normal and official process is kind of dream-crushing. Who knows, maybe as technology advances, hopefully, we can make all of this happen without harmful side effects, aid our ailing ecosystems, and visit some mammoths on a safari vacation!

CRISPR Mini | New Territory Unlocked

For over a million years, DNA has centered itself as the building block of life. On one hand, DNA (and the genes DNA makes up) shapes organisms with regard to physical appearance or ways one perceives the world through such senses as vision. However, DNA may also prove problematic, causing sickness/disease either through inherited traits or mutations. For many years, scientists have focused on remedies that indirectly target these harmful mutations. For example, a mutation that causes cancer may be treated through chemotherapy or radiation, where both good and bad cells are killed to stop unchecked cell replication. However, a new area of research, CRISPR, approaches such problems with a new perspective.

The treatment CRISPR arose to answer the question: what if scientists could edit DNA? This technology involves two key components – a guide RNA and a CAS9 protein. Scientists design a guide RNA that locates a specific target area on a strand of DNA. This guide RNA is attached to a CAS9 protein, a molecular scissor that removes the desired DNA nucleotides upon locating them. Thus, this method unlocks the door to edit and replace sequences in DNA and, subsequently, the ways such coding physically manifests itself. Moreover, researchers at Stanford University believe they have further broadened CRISPR’s horizon with their discovery of a way to engineer a smaller and more accessible CRISPR technology.

This study aimed to fix one of CRISPR’s major flaws – it is too large to function in smaller cells, tissues, and organisms. Specifically, the focus of the study was finding a smaller Cas protein that was still effective in mammalian cells. The CRISPR system generally uses a Cas9 protein, which is made of 1000-1500 amino acids. However, researchers experimented with a Cas12f protein which contained only 400-700 amino acids. Here, the new CasMINI only had 529 amino acids. Still, the researchers needed to figure out if this simple protein, which had only existed in Archaea, could be effective in mammals that had more complicated DNA.

To determine whether Cas12f could function in mammals, researchers located mutations in the protein that seemed promising for CRISPR. The goal was for a variant to activate a protein in a cell, turning it green, as this signaled a working variant. After heavy bioengineering, almost all the cells turned green under a microscope. Thus, put together with a guide RNA, CasMINI has been found to work in lab experiments with editing human cells. Indeed, the system was effective throughout the vast majority of tests. While there are still pushes to shrink the mini CRISPR further through a focus on creating a smaller guide RNA, this new technology has already opened the door to a variety of opportunities. I am hopeful that this new system will better the general well-being as a widespread cure to sickness and disease. Though CRISPR, and especially its mini version, are new tools in need of much experimentation, their early findings hint at a future where humans can pave a new path forward in science.

What do you think? Does this small CRISPR technology unlock a new realm of possibility or does it merely shed light on scientists’ lack of control over the world around us?

CRISPR: A Possible Solution to Genetic Diseases?

A few decades ago in science fiction, there were talks of things like genetic modification in babies. This was more along the lines of creating the ‘perfect’ human, rather than using genetic modification to stop certain genetic illnesses. An example of this is in the 1997 movie, Gattaca, where we see an unmodified (genetically) person struggle to live in a world of genetically modified people. While it is fiction, it showed how being able to alter someone’s genetic flaws can go a long way. Despite, at the time, this seeming to just be science fiction, some of these concepts of gene alteration might become reality. These concepts becoming reality would all be due  to CRISPR.

CRISPR logo

Some of you might be thinking, “what is CRISPR?,” and that’s okay because before researching it I was thinking the same thing. CRISPR is a type of genetic engineering technique in molecular biology. This technique allows for the modification of genomes in a living organism. This technique is actually based off of CRISPR-Cas9 antiviral defense system, which can cut genomes. This has inspired CRISPR to contain Cas9 nuclease complexed with gRNA. This is the sent into a cell and is able to cut a cell’s genome at a certain position. This allows for specific genomes to be removed, as well as allowing new ones to be added. So in summary, CRISPR is a method of removing certain genomes of a cell, and in some cases replacing and/or adding a genome as well.

Now that CRISPR has been explained and we know what it is as well as how it works, we are now able to look at studies involving it. While CRISPR seems great and all, Heidi Ledford posted an article about how the use of CRISPR in embryos can cause some unwanted changes to the embryo. While experimenting, researches found that the use of CRISPR on an embryo can not only cause unwanted changes at the genome target site, but it can also cause changes near the genome target site. While some of you may think that the pros out-weigh the cons in this instance, geneticist Gaétan Burgio states that, “the on-target effects are more important and would be much more difficult to eliminate.” The on-target effects (negative) are so bad that it may not be worth doing even if it is to eliminate genetic diseases.  The idea that the cons outweigh stopping a genetic disease shocked me, as in our biology class we talked about genes and genetic diseases, and how even though they can be extremely rare, they can be irreversible, life changing, and in some cases fatal. This rejects the idea that the pros could out-weigh the cons, which puts a pin in this genetic modification breakthrough.

After looking at CRISPR as well as the research shown on genetic modification of embryos, I have realized how far we still are from elimination of genetic diseases. Despite issues arising in the experiment, I hope that they can put CRISPR to good work in order to stop the seemingly impermeable genetic diseases. And who knows, if we can master genetic modification with CRISPR, the ideas presented in Gattaca could soon seem like reality.

 

 

Why COVID-19 Messes With Smell and Taste

Have you ever wondered why only some people lose their smell when they contract covid-19? The answer to this question is more complicated then it seems. The real answer requires a deep dive into genetics and DNA.

Earlier in the pandemic we were told that if you were to lose taste or smell then this is a likely sign you have the virus. Now we are understanding that not all people have this “common” symptom. A study was done to show the true numbers behind this phenomenon. Out of 70,000 adults who contracted the virus, 11% of adults with a certain genetic makeup on chromosome 4 were more likely to lose their smell and taste. I then wondered how can one chromosome have an effect on losing taste?

I found my answer. As it turns out, the two genes: UGT2A1 and UGT2A2 are two genes that help people smell. These genes are located right next to chromosome 4 which is why these people are more prone to losing their smell when they contract the virus. Additionally, the actual pathways that cause our ability to smell and taste are over and under performing depending on the person. Similar to our Biology class, everyone has different sets of genes. Some genes can be closer to others. Therefore, only some people are affected by this lack of smell and taste if their UGT2A1 and UGT2A2 genes are closer to the location of the variant.

COVID-19 Icon

 

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