BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: Genes (Page 1 of 3)

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

 

How a Genetic Mutation Makes Rabbits do Handstands Rather than Hopping

Erin Garcia de Jesús in sciencenews explains on a genetic level why the domesticated rabbit, Sauteur d’Alfort, does a handstandRabbits of Okunoshima, August 2018 (03) to move quickly rather than hopping. The cause of this change in their behavior is due to a defective gene likely linked to their limb movement.

Scientists completed a study not only to understand the rabbit’s handstands but Leif Andersson claims it would contribute “to our basic knowledge about… how we are able to move”. To find out where the mutation occurred, scientists crossed Sauteur d’Alfort rabbits that do handstands with New Zealand female rabbits that hop. They scanned the genetic blueprints of their offspring and looked for mutations that didn’t appear in the offspring. They found a mutation in the RORB gene and concluded that it was a likely explanation for the rabbit’s handstands. In rabbits that have the mutation, there is much less RORB than in rabbits that don’t, this is because the “change creates faulty versions of the genetic instructions that cells use to make proteins”. A lack of RORB protein in interneurons, the spinal cord nerve cells, will cause the rabbits to lack the ability to coordinate their hind limbs. They are still able to walk normally when they are moving slowly by alternating their front and hind legs normally. Since hopping requires the synchronization of the hind legs the mutation prevents them from doing so, so “all rabbits with a RORB mutation use their front paws to move quickly,” Carneiro says. Though they were able to understand how the mutation in one gene affects the rabbit’s movements, the gene could potentially be affecting the rest of the rabbit too, but they are unsure. If the scientists could understand how the genetic defect affects the body on a more broad scaleGregor Mendel 2 then they could understand the way that all animals move. Though the rabbits may not ever be able to hop, these findings can help researchers to develop ways to repair human bodies when there are defects in the RORB protein that could potentially cause disease. 

In AP Biology this year, we learned about Mendel’s laws of inheritance and all about genetics. He studied how genes are passed down from the parent generation, recessively or dominantly. Mendel stated that a mutation in a single gene can cause a disease that will be inherited. In connection to the rabbit’s genetic mutation, a lack of the RORB protein causes the rabbits to have insufficient limb control, but the presence of the protein makes the rabbits ‘normal’. 

Comment below if you have ever heard of a genetic mutation that caused an animal to move in an abnormal way, I’d love to hear. I did some research and these Sauteur d’Alfort rabbits are incredibly rare and originate from France. Ironically enough, in French, their name means Alfort’s Jumpers! I also found a video of one of them if you want to watch it… click this link.

CRISPR Gene Editing: The Future of Food?

Biology class has taught me a lot about genes and DNA – I know genes code for certain traits, DNA is the code that makes up genes, and that genes are found on chromosomes. I could even tell two parents, with enough information, the probabilities of different eye colors in their children! However, even with all this information, when I first heard “gene editing technology,” I thought, “parents editing what their children will look like,” and while this may be encapsulated in the CRISPR gene editing technology, it is far from its purpose! So, if you’re like me when I first started my CRISPR research, you have a lot to learn! Let’s dive right in!

CRISPR

Firstly, what is CRISPR Gene Editing? It is a genetic engineering technique that “edits genes by precisely cutting DNA and then letting natural DNA repair processes to take over” (http://www.crisprtx.com/gene-editing/crispr-cas9).  Depending on the cut of DNA, three different genetic edits can occur: if a single cut in the DNA is made, a gene can be inactivated; if two separate DNA sites are cut, the middle part of DNA will be deleted, and the separate cuts will join together; and if the same two separate pieces of DNA are cut, but a DNA template is added, the middle part of DNA that would have been deleted can either be corrected or completely replaced. This technology allows for endless possibilities of advancements, from reducing toxic protein to fighting cancer, due to the countless ways it can be applied. Check out this link for some other incredible ways to apply CRISPR technology!

In this blog post however, we will focus on my favorite topic, food! Just a few months ago, the first CRISPR gene-edited food went on the market! In Japan, Sicilian Rouge tomatoes are now being sold after the Tokyo-based company, Sanatech Seed, edited them to contain an increased amount of y-aminobutyric acid (GABA). “GABA is an amino acid and neurotransmitter that blocks impulses between nerve cells in the brain” (https://www.scientificamerican.com/article/crispr-edited-tomatoes-are-supposed-to-help-you-chill-out/). It supposedly (there is scarce scientific evidence of its role as a health supplement) lowers blood pressure and promotes relaxation. In the past, bioengineers have used CRISPR technology to “develop non-browning mushrooms, drought-tolerant soybeans and a host of other creative traits in plants,” but this is the first time the creation is being sold to consumers on the market (https://www.scientificamerican.com/article/crispr-edited-tomatoes-are-supposed-to-help-you-chill-out/)!

Tomatoes

So, how did Sanatech Seed do it? They took the gene editing approach of disabling a gene with the first method described above, making a single cut in the DNA. By doing so, Sanatech’s researchers inactivated the gene that “encodes calmodulin-binding domain (CaMBD)” in order to increase the “activity of the enzyme glutamic acid decarboxylase, which catalyzes the decarboxylation of glutamate to GABA, thus raising levels of the molecule” (https://www.scientificamerican.com/article/crispr-edited-tomatoes-are-supposed-to-help-you-chill-out/). These may seem like big words, but we know from biology that enzymes speed up reactions and decarboxylation is the removal of carbon dioxide from organic acids so you are already familiar with most of the vocabulary! Essentially, bioengineers made a single cut in DNA inside of the GABA shunt (a metabolic pathway) using CRISPR technology. They were therefore able to disable the gene that encodes the protein CaMBD, and by disabling this gene a certain enzyme (glutamic acid decarboxylase) that helps create GABA from glutamate, was stimulated. Thus, more activity of the enzyme that catalyzes the reaction of glutamate to GABA means more GABA! If you are still a little confused, check out this article to read more about how glutamate becomes GABA which will help you better understand this whole process – I know it can be hard to grasp!

After reading all of this research, I am sure you are wondering if you will soon see more CRISPR-edited food come onto the market! The answer is, it depends on where you are asking from! Bioengineered crops are already hard to sell – many countries have regulations against such food and restrictions about what traits can actually be altered in food. Currently, there are some nutritionally enhanced food on the market like soybeans and canola, and many genetically modified organisms (GMOs), but no other genome-edited ones! The US, Brazil, Argentina, and Australia have “repeatedly ruled that genome-edited crops fall outside of its purview” and “Europe has essentially banned genome-edited foods” (https://www.scientificamerican.com/article/crispr-edited-tomatoes-are-supposed-to-help-you-chill-out/). However, if you are in Japan, where the tomatoes are currently being sold, expect to see many more genome edited foods! I know I am now hoping to take a trip to Japan soon!

Thank you so much for reading! If you have any questions, please ask them below!

T-Cells: A New Fighter Against Cancer?

Cancer is something that most have heard of, and worry about. There are so many different types of cancer, and they are all taken extremely seriously due to it being able to cause more harm if left unattended to. When people think of cures and treatments for cancer, the most common one that is used across many different kinds is chemotherapy. While useful, it is not always effective, and it does not work on every type of cancer. Despite chemotherapy being the leading treatment against cancer, there are talks of a new treatment that may treat all cancer.” 

BBC reported a study done that mentioned that there may be A newly-discovered part of our immune system could be harnessed to treat all cancers.” However, before we look at this new possible treatment, we should first dive into how chemotherapy works. Chemotherapy is the process in which we use drugs to destroy cancer cells. While it can not always completely destroy cancer cells, it still aims to either keep the cancer cells from growing, dividing, and/or making new cells. The drugs in chemotherapy are meant to attack rapidly dividing cells, which is usually what cancer falls under. Despite this seeming all great, there are some drawbacks. Other rapidly dividing cells in our body include the lining of our stomach and hair, which is why some people lose hair and have digestive problems when undergoing chemotherapy. With all this in mind, it is important to note that chemotherapy is not always used for the destruction of cancer, but sometimes to weaken it in order to work as an aid to other treatments. All of this goes to show chemotherapy’s versatility, accessibility, and utility.

Now that we know the traditional treatment to most cancers, chemotherapy, we can look at the potentially new treatment and how well it works and if it is the new best option.

This new study uses our immune system to help treat cancer, whereas chemotherapy uses drugs. These researchers studied how the immune system naturally responded to cancerous tumors. Normally, T-cells are used to fight all kinds of infections, but are not always effective against combating cancer. However, the T-cells that the researchers have discoveredcould attack a wide range of cancers.” They even stated that there’s a chance to treat every patient.” What made this T-cell different is that its receptors, which are what allow normal T-cells to detect certain infections, are able to detect most cancerous cells. Not only could they detect them, but they can kill lung, skin, blood, colon, breast, bone, prostate, ovarian, kidney and cervical cancer cells. This particular T-cell interacts with a molecule called MR1, so they are trying to figure out how to pair these together consistently, reliably, and safely. 

This cancer treatment seems to work during all stages of the cancer cell’s life. Normally, as we learned in bio class, cancer cells are typically created from a gene mutation in either the oncogene or tumor-suppressor genes. These genes normally stop or terminate the soon to be cancer cell, but when mutated they can not do their job properly, thus leading to a cancer cell being created and duplicating unchecked. Once it is at this stage, the T-cells are able to do their work. I think that this is an interesting treatment as it can be used to help treat most stages of cancer, and could potentially be taken pro-actively in order to activate these T-cells in the body, making them always ready to fight off any cancerous cells. I believe that this could make it a safer, and more proactive version of chemotherapy. 

This new cancer treatment might seem promising, but there is no timeline on when a mass-produced reliable treatment using this method will be complete. Despite this, it is important to know that this could hopefully be an option for many in the future, and can hopefully combat and win the worldwide fight against cancer. 

 

How are new COVID variants identified?

COVID variants are of high concern for scientists studying the disease. Some variants can be more infectious or cause more severe illness. Additionally, some variants can evade vaccines by having different surface proteins than the variant the vaccine was created for. This causes the antibodies produced from the vaccine to be less effective against other variants. In AP Biology class we discussed how the Delta Variant, first identified in December 2020, has a different spike protein structure than the original virus from which the vaccine was created from. This allows the variant to be more infectious, and make the vaccine less effective against it. But, what are COVID variants? And how are they discovered? Hand with surgical latex gloves holding Coronavirus and A Variant of Concern text

COVID variants are “versions” of the virus with a different genetic code than the original one discovered. However, not every mutation leads to a new variant. This is because the genetic code of the virus codes for proteins. Some mutations will not change the structure of the protein and thus not change the virus. So, COVID variants can be defined as versions of the virus with a significantly different genetic code than the original virus.

To detect new COVID variants, scientists sequence the genetic code of virus which appears in positive COVID tests. Scientists look at the similarity of the genetic sequences they find. Then, if many of the sequences they get look very similar to each other, but different to any other known virus, a variant has been discovered.

To sequence the RNA of the virus, scientists use what is called Next Generation Sequencing (NGS). To understand how NGS works, it is best to start with what is called Sanger Sequencing. Sanger Sequencing utilizes a modified PCR reaction called chain-termination PCR to generate DNA or RNA fragments of varying length. The ending nucleotide of each sequence is called a ddNTP, which contains a florescent die corresponding to the type of nucleotide. The addition of a ddNTP also terminates the copying of the particular sequence. The goal of this PCR reaction is to generate a fragment of every length from the start to the end of the sequence. The sequences can then be sorted by length using a specialized form of gel electrophoresis. The sequence is then read by using a laser to check the color of the fluorescent die at the end of each sequence. Based on the color and size, the nucleotide at that position of the genomic sequence can be found.

Sanger Sequencing Example

The difference with NGS is that many sequences can be done in parallel, allowing for very high throughput. In other words, with NGS many COVID tests can be sequenced in once.

Genes: They are influential in more ways than one

The article entitled, “Your Friends May Be In Your Genes,” discusses the study Virginia Commonwealth University researchers led on the influence of genes on the choices that we make when developing social connections.  Researchers claim that as people mature, their genes become progressively more critical in how they choose their friend groups. The discoveries in the study reflect which people are most susceptible for substance use or externalizing behaviors in their lifetime, based on the company they keep.

Comprised of individuals who were part of the Virginia Twin Registry, the study looked into the role of genetic factors in decision making amongst men during their adolescence, using roughly 1,800 male twin pairs ranging from teenage years to early adulthood, and involved interviews used to help explain how social groups can influence deviant behaviors.  Specifically, the study showed that genes can impact how individuals select their peer groups, and that those groups affects one’s tendency to engage in antisocial behaviors. Because peers have a significant effect on promoting and/or discouraging deviant behaviors and also oftentimes provide substances for abuse, an individual’s social environment can play a critical role in his/her life choices.

As mentioned in the article, “Why Twin Studies,” Twin studies have long been used as a means to identify different illnesses and disorders because they allow researchers to determine the the various influences on certain traits.  If a trait is similar between individuals who have the same genes, like identical twins, but not so in fraternal twins, a case can be made for a genetic link.  If a trait is similar between fraternal twins, but not so in identical twins, then a case can be made for environmental impact.

In the article, “Its Nature and Nurture: How Our Genes and Our Friends Shape the Way We Live Our Lives,” further support is given to the link between genes, environment, and risky behaviors when it points out that more educated Americans are less likely to smoke.  Since educated people tend to surround themselves with like minded people who find smoking unacceptable, those who are socially connected in this way are not usually smokers.  This suggests that people who have genes linked to educational success are less likely to have genes linked to smoking and vice versa.

Genes are segments of DNA that contain the instructions for the production of proteins.  Cells contain organelles, called ribosomes that are responsible for producing proteins that control physical traits.  Genes provide the information for which amino acids need to be joined to build each protein.

Personally, I think genes are interesting not only because they control the traits that we posses, but also because they can be linked to who we chose to surround ourselves with. It is our social choices that can then determine behaviors we participate in.

 

 

Forbidden Baby Editing

We all at this point in life have come to know what gene editing is. The technology for it is slowly and forever becoming more and more advanced. The scary thing about editing genes is the fact that we have to potentially affect a baby’s life their entire time alive. It has many different problems which is why its going to take a long time for it to fully get approved in the hospital.

Well unfortunately in an article found here there was a fright to figure out that someone had actually edited the genomes of some babies without people knowing. Many scientists condemned scientist He Jianku as it came to light that he had done something that the science was not ready for yet. He used CRISPR Cas9 tech in order to alter some genes of a few babies. The definition of CRISPR is here but basically it is a general tech to edit the genomes of babies that haven’t been born yet. People were up in arms about the process because he had bypassed the ethical laws and needed up editing the genes of a real live human. People in the science community go on to say that the CRISPR technology just isn’t ready to be executed on a human. There needs to be many more trials before it is used on a person for real. There is progress to make sure this doesn’t happen such as fines and bans from research however they are trying to make sure that it doesn’t happen at all. It gives scientists a bad name and he is trying his best to not let that happen. Technology will always advance and the hard part is trying to make sure that tech is ethical. Hopefully this gives insight to how we can prevent things like this happening in this day and age

How the “unknown” of the human gut microbiome gets in the way of metagenomic studies…

Did you know that the greatest concentration of bacteria lives in your gut? At two or three years old we have a balanced microbiome. While we know a lot about the human gut microbiome, there is a lot that is unknown about it. There has been a lot of improvement in finding an “unknown microbiome” for example, shotgun metagenomics enables researchers to take a sample of all genes in all organisms and allows them to find an abundance of microbes in many different environments.

What we know: 25 Phyla, ~2,000 Genera, ~5,000 Species, ~80% Metagenome mappability, and 316 million genes

What is unknown?: Undetected unknowns, hidden taxa and strain-level diversity (~20% sequences not matching microbial genomes), functional unknowns (~40% genes without a match in functional databases)

For example, one study where researchers studied a stool sample from 2 lean African men and a stool sample from 1 obese European. In the stool, they found 174 new species never seen in the human gut before and 31 new genome species (which can help in later studies). Found within these new species was, Microvirga Massiliensis which has the largest bacterial genome acquired from a human, along with Senegalvirus which is the largest virus in the human gut. We definitely know a lot more about the human gut microbiome than we did, even though there is a long way to go.

However, organizing large numbers of draft genomes from uncharacterized taxa is challenging, and while performing well for bacteria, assembly-based metagenomic tools are less effective when targeting new eukaryotic microbes and viruses.

The human gut microbiome intestines in an obese person vs. a lean person

To make improvements in uncovering “hidden strain-level diversity” it is vital to alter sample-specific associations from the metagenomes and to additionally incorporate as many genomes for each species in reference databases. Most species are “open”, meaning they don’t have an upper bound on the size of accessory genomes and it may seem impossible to reclaim all strain-level diversity; however, preserving “the effort of cataloguing strain variants remains crucial for an in-depth understanding of the functional potential of a microbiome.”

The difficulty is that the microbiome contains viruses. The “functional unknown” of the human gut microbiome is the broadest and most challenging to delve and study further into because there is little known about understanding its pathways and genes. There is one creation though, that helped try and find out what was “unknown” about the microbiome, called the Integrated Gene Catalogue. The Integrated Gene Catalogue of the human gut microbiome which consists of 10 million genes. It groups genes into thresholds, thus the genes then fall into sub-units of gene-families. Locating these genes is only a small part of finding out what they actually do. For example, out of 60.4% of the genes that were annotated, 15-20% of the genes have been discovered, but are stilled labelled “function unknown.” These results show how little is known about genes, their functions, and what is current in microbial communities. There is not enough investment in microbiome research. It is difficult because there could be viruses that can be discovered; however, not enough time is being put into finding it.

Lastly, there is a lot of research going into the human gut microbiome. For example, Fecal microbiome transplantation is where stool from a healthy donor gets placed into the other patients intestine, this transplant usually occurs when more bad bacteria take over the good bacteria in the intestine. However, it could cause more disease which is why further investigation in the human gut can solidify that transplantation could overall prevent a bad bacteria take over. The microbiome field is open to all technologies. Understanding the function of the microbiome still remains the largest challenge researchers face, along with the biggest challenge that “targeting specific genes are irreplaceable”, technology should be able to provide solutions (including microbial transcriptome, metabolome, and proteome, and the automation of cultivation-based assays to scale-up the screening of multiple taxa and genes for phenotypes of interest.)

 

Cracking the Code one Gene at a Time

Cells are one of the most important objects in the human body, yet scientists still have yet to truly understand the underlying mechanics. Recently researchers have observed how RNA transcription occurs in real, live cells. For the longest time scientists have observed RNA transcription extracellularly. Until now they have only been able to observe how RNA polymerase 2, a DNA copying enzyme, and other enzymes “by breaking cells apart and measuring the activity… outside the cellular environment.”

 

The molecules involved in RNA transcription have been studied profusely, but only frozen in time. Now we can use “a highly specialized optical microscope” to watch how RNA polymerase copies DNA into mRNA. Researchers then labeled certain molecules with a tag so that they glowed when looked at. An issue with this method, though, is that there are so many of these molecules in the nucleus that if we were just to examine the reactions after adding the fluorescent tag, we would just have a glowing nucleus. The scientists have combated this by suppressing the signals from other reactions. This, along with the ultra-sensitive microscope allows us to focus on one gene and transcription occurs for it.

Through this new technique, we now have a much more detailed and intricate picture of how DNA, RNA, and enzymes function in transcription. This process can be replicated for many more reactions and will help us understand bounds more about ourselves and how we truly work.

I am personally very excited to see what new concepts and techniques will be discovered from this breakthrough. Genetics is the future of biology and using this to crack the code is one step closer to curing many genetic diseases. Combining this with other genetic breakthroughs like CRISPR is a cause for excitement in the future of biology. If you have any other ideas about why this could be useful please comment below.

 

The Rice That Can Clone Itself

A team of scientists has discovered that through the use of CRISPR, they were able to create a rice plant that can asexually reproduce. The problem with previous strands of genetically modified rice plants, those bread to have a higher yield, is that their progeny did not always carry this desired trait. So farmers have to buy new genetically modified seeds every year to ensure that they will get that same yield.

Image result for rice grains

That is where the magic of CRISPR comes into the equation. The first step in the process was editing the eggs of the plant by implanting a promoter that allows the egg to start the embryo growing process without a sperm. One issue still lingered, the process of meiosis that was occurring could not produce viable offspring because it only had half of the genetic material that the progeny would need. Another team of scientists from the French National Institute for Agricultural Technology discovered that by using CRISPR to turn off three specific genes they could stop the meiosis process and allow the plant to reproduce asexually.

Image result for rice plant

This process is still only 30% efficient at this stage. However, the offspring they do produce are able to asexually produce more clones of themselves. Now the process starts to try and make this process more efficient. I think these plants could have a major impact on the agricultural industry, especially with food shortages becoming more present as the human population rapidly increases.

What do you think? Have we overstepped our bounds by editing nature? Or have we pioneered a new solution for the world hunger question on everyone’s minds?

Could Messenger RNA Be the Future Chronic Disease Treatment?

What is mRNA and what makes it a good treatment option?

Messenger RNA (mRNA) sends signals to the cells to make certain proteins by changing the genetic coding. So mRNA has the potential to treat a variety of diseases because it can induce cells to make therapeutic proteins. This essentially makes the patient’s body cells into a treatment factory which would give patients a less invasive treatment option.

One of the obstacles with this treatment is how to deliver mRNA to the diseased area safely and efficiently. Researchers at MIT have found a new way to provide patients with mRNA. They made an inhalable form of mRNA. The goal would be to administer the mRNA similar to an asthma inhaler where powered mRNA medication would be sprayed into the lungs but as of now, the medication is only available in nebulizer form. However, there needed to be a way to stabilize the mRNA molecules using an aerosol method. So the researchers experimented with positively charged beta-amino esters which are biodegradable and are more easily broken down by the body. The upside to using a biodegradable material is that there would be a minimal accumulation of the substance in the area it was administered. Accumulation would cause unwanted side effects to the patients’ health.

To test out their new product MIT scientists put the mRNA molecule and polymers in spheres.  Then suspended those spheres in water droplets and distributed a mist through a nebulizer to mice. But the mRNA molecules that they put into the spheres coded for the production of the bioluminescent protein luciferase. Using the code for the bioluminescent luciferase, the researchers would be able to see if the mRNA had effectively made the protein that it coded for if it glowed. 

After 24 hours since administering the medication, the mice were producing bioluminescent proteins in their lungs which hints that eventually scientists could inject the code for therapeutic proteins in the mRNA and the cells would respond.  But as the mRNA levels dropped so did the protein production. That showed that only with repeated doses of the medication the mice would be able to continuously produce their own proteins. They also found that mRNA was evenly distributed throughout the five lobes of the lungs so the mRNA reached all the areas of the lungs which would be helpful in treating cystic fibrosis. This process could be the future treatments for chronic lung diseases as researchers work to make this product into inhaler form instead of the nebulizer for convenience purposes.

Microbiome Genes have Macro-significance

Ever been told that the little things matter in life? This same proclamation that you’ve been told by your elders rings true in your gut: one small modification to your human gut microbiome (a batch of bacteria that call your digestive tract home) can have drastic effects on your metabolism.

A. Sloan Devlin, assistant professor at Harvard medical school, carried out a study that proved the importance of the gut microbiome. She first located the gene in “an abundant gut bacterium” for an enzyme that processes bile acids. She then removed that gene from the bacterium. Next, she “colonized” “germ-free” mice with one of two types of the gut bacterium: either with the bile-processing enzyme or without the bile-processing enzyme. The results were surprising.

Credit: mcmurryjulie on pixabay

After both mice were fed the same high-fat, high-sugar diet, the mice without the bile-processing enzyme “had more fat in the liver and gained weight much more slowly than the other group. They also used proportionately less fat and more carbohydrate for energy.” Changing one single enzyme in a gut bacterium appears to change “whether the host is using [primarily] fats versus carbohydrates” for energy.

Even more staggering was the “correlation of lean body mass to energy expenditure.” Typically, in humans and mice, the more lean body mass an organism has, the more energy it expends. However, for the mice without the bile-processing enzyme, this relationship “broke down.” Devlin hypothesizes that this change could be due to a “signaling,” a process in which “physical states in the body trigger a cascade of genes to switch on or off.” Researchers can use this knowledge to treat diseases: figure out which microbiome bacteria activate which genetic switches, and better treatment for genetic problems such as, acid imbalances, metabolic disorders and obesity, may become a reality.

Devlin is sure to stress that this groundbreaking microbiome research is just her “first step.” Although this study was carried out on “germ-free” mice, Devlin dreams that one day she may use her research to improve the health of her own species: as Devlin states, her research brings her “one step closer to humans.”

 

A Gene In Your Ears For Sour Taste?

Unlike the other four human tastes, our process of detecting sourness has always been a mystery, and scientists were definitely not expecting to find the answer in a  protein normally found in the inner ear.

https://pxhere.com/en/photo/994259

This protein, coded by the gene scientists refer to as Otop1, usually functions as part of the vestibular system to maintain balance. Given this more commonly known function of the protein, scientists were shocked to find its use for both balance and detecting the acids often associated with sour taste. The association is actually not as far- fetched as one might think. Otop1 codes for the synthesis of calcium carbonate crystals which rest on the hairs of the inner ear and detect gravity to help humans stand upright. Researchers found that the tongue also uses these crystals to detect sour taste. Calcium carbonate, a relatively basic compound, dissolves when it comes into contact with acid, which reaction can be detected by the brain and interpreted as sour taste.

How could such a protein find its way to use in both our senses of balance and taste?

The answer lies in evolution. If a certain protein proves advantageous over generations, organisms with it in surplus may evolutionarily find other uses for the it. Recently scientists have actually found several proteins for sensory organs that double as homeostatic sensors in other tissues. Otop1 is only one of many; smell receptors are found in the kidney in surplus, as are sweet taste receptors in the bladder.

Although we have unearthed a lot about the human body over the years, there is always so much more to learn!

Fighting the mosquito disease problems with… mosquitos?

Since the discovery of CRISPR-Cas9 system (Clustered Regularly Interspaced Short Palindromic Repeats), gene editing has become a highly debated topic. One of the reasons backing the use of CRISPR-cas9 is to prevent diseases. These diseases include mosquito-borne diseases such as zika, dengue fever, and malaria.  Malaria in particular kills around 3,000 children every year. Various groups of scientists have worked on genetically modifying mosquitos to stop the spread of malaria by making female offspring sterile and unable to bite, making male offspring sterile, or making mosquitos resistant to carrying diseases. A point of concern was if the modified gene would stay relative and would carry from generations. In order to make offspring, genes from both parents must be used, resulting in the offspring carrying the modified gene only half the time.  In particular cases, mutations would occur in the altered DNA, which nullified the genetic changes.  This has been solved by developing a gene drive, which makes the desired gene dominant and occur in the offspring almost 100% of time.  This entails almost the entire mosquito population could have this modified gene in as little as 11 generations.

Image by Author

Recently, the government of Burkina Faso, a small land-locked nation in west Africa, has approved for scientists to release mosquitos that are genetically modified anytime this year or next year.  The particular group of mosquitos to be released first is a group of sterile males, which would die rather quickly.  Scientists want to test the impact of releasing a genetically modified eukaryotic organism in the Africa. It is the first step in “Target Malaria” project to rid the region of malaria once and for all.

 

One of the major challenges in gaining allowance to release the genetically modified species was the approval of the residences, who lack words in the local language to describe genetics or gene editing.  Lea Pare, who leads a team of scientists modifying mosquitos, is working with linguists to answer questions the locals may have and tp help develop vocabulary to describe this complex scientific process.

What do you think about gene editing to possibly save millions?

Read the original article here.

View a video explaining how scientists can use genetic engineering to fight disease here.

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