BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: #CRISPR/Cas9 (Page 3 of 5)

A New Mosquitoes Exterminator: CRISPR

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On March 16, 2022

In Student Post

Mosquitoes might be just pesky little insects that might start appearing again in a few months. They leave their saliva in your skin, and this causes an itchy bump. But in other parts of the world. Estimates report that mosquitoes have killed up to 52 billion people in history by spreading malaria, yellow fever, and dengue. It is currently killing 1 million people per year, even with advanced medicine and healthcare around the world. Doesn’t that horrifying statistic shock you? 

Aedes aegypti

A close shot of Aedes aegypti

To drastically lower this number, researchers took a smart approach and decided to eliminate the source of the problem. They decided to use CRISPR to genetically alter the male flies so that they become sterile.  Professor Craig Montell from UC Santa Barbara altered the gene of Aedes aegypti, the main type of mosquito that transmits dengue, yellow fever, Zika, etc. 

Previously, scientists just radiated and applied chemicals to sterilize male mosquitoes in hopes to alter their genes since “there are enough genes that affect fertility that one will likely be altered,” making them infertile. However, this would leave, many of the mosquitoes to be sick and die prematurely since other genes that don’t relate to fertility are also changed.

Using CRISPER/Cas9, researchers removed B2t, a gene that specifically affects male fertility in mosquitoes. Unlike in previous efforts, the sterile mosquitoes were completely healthy. 

This whole effort to sterilize insects is part of a greater method called the sterile insect technique (SIT). Scientists release way more sterile insects than there exist in the wild. The population will crash as females will not be mating with a lot of males that are capable of making offspring. A benefit of releasing males instead of females is that males feed on nectar, not blood,  so it will not cause major disturbance to communities.

To sexually reproduce, a sperm cell must meet an egg. Each gamete is a haploid that has a single set of chromosomes. The sperm and egg combine to produce a zygote making it a diploid with a complete set of chromosomes. If a male is sterile, then they are not able to produce or release their sperm, making it impossible for those insects to reproduce.

The effect of this technique is more effective after each cycle, so when you release the same amount of mosquitoes after 3 cycles, the population change will be way more drastic. A downside to this is that sterile male mosquitoes need to be reintroduced after they die off since they cannot pass on their mutated gene.

Although researchers have successfully identified a way to isolate the gene and remove it to make male mosquitoes fertile, they still needed to find the optimal ratio of lab mosquitoes to wild type to ensure that they do not wipe out the species in an area since that has dramatic effects on the whole ecosystem. The researchers conducted many trials and found that, in a week, a ratio of about “5 or 6 sterile males to one wild-type male” decreased female fertility by 50% while, a ratio of 15:1 suppressed female fertility to about 20%, where it leveled off. So depending on the situation, they now release the more precise amount. 

I think that this is one of the brilliant uses of CRISPR, and it only goes to show how far we can go if we master this technique. An ethics question that this research brings up is, do humans have the right to wipe out an entire species just because it is causing harm to humans?

CRISPR Gene Editing: The Future of Food?

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On March 16, 2022

In Student Post

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!

Forbidden Baby Editing

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On January 21, 2020

In Student Post

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

The First “in vivo” CRISPR-Cas9 Gene Editing

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On January 21, 2020

In Student Post

At the start of the new year all of the scientists working in different fields being to create a schedule of perceived accomplishments that will occur in regard to their specific field of study. In the term of the people working with CRISPR, they speculate that the first in body injection in order to conduct real time genome editing will occur in 2020. Prior to this year, CRISPR has been used to edit and alter the DNA of red blood cells outside of the body, but the scientists working with this new form of biological technology belief that this year it will be used the way it is intended to be used.

CRISPR was originally found in 2012 inside bacteria in order to help stop viruses from infecting them. Scientists saw the possible benefit of this in humans and through years of research discovered that CRISPR can help place another enzyme Cas9, which snips out parts of DNA, in a correct spot on the genome to alter and edit a person’s DNA code. While over time some scientists have wondered about the ethics of this new discovery, most are excited by all of the possibilities that CRISPR has on curing diseases.

Currently, the reason that CRISPR-Cas9 has become a talking point recently was due to the fact and difference between gene editing “in vivo” versus gene editing “ex vivo”, meaning within the body or outside the body. Scientists working with CRISPR have been able to understand how editing “ex vivo” works. They are able to see the genes they want to edit and watch the process occur. This is also easier for the scientists because if the editing messes up, they do not need to reinsert the altered cell back into the body. On the other hand, “in vivo” gene editing is much more efficient and can be completed through a simple injection, but may cause dangerous consequences, such as cancer, if a mistake is made in both the scientists’ coding of the CRISPR or in the process done by the CRISPR itself.

Now that scientists are starting to attempt to move from “ex vivo” editing to “in vivo” editing, all of these questions and issues are being brought up. With lots of labs around the country working on moving into “in vivo” editing and an FDA approval for the procedure, the first CRISPR-Cas9 “in vivo” gene editing is bound to happen soon. Hopefully, this new biological technology does its job properly and gives hope to those who have various currently seemingly incurable disease. If successful, CRISPR could revolutionize medicine itself to make it more efficient and effective. Feel free to comment about how you think CRISPR will do in the first “in vivo” test and how it could effect life later on.

Can your diet’s effect on gut bacteria play a role in reducing Alzheimer’s risk?

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On November 11, 2019

In Student Post

Could following a certain type of diet affect the gut microbiome in ways that decrease the risk of Alzheimer’s disease? According to researchers at Wake Forest School of Medicine, that is a possibility.

In a small study, researchers were able to identify several distinct gut microbiome signatures in study participants with mild cognitive impairment (MCI), but not in the other participants with normal cognition. Researchers found that these bacterial signatures correlated with higher levels of markers of Alzheimer’s disease in the cerebrospinal fluid of the participants with MCI. Additionally, through cross-group dietary intervention, the study also revealed that a modified Mediterranean-ketogenic diet resulted in changes in the gut microbiome and its metabolites that correlated with reduced levels of Alzheimer’s markers in the members of both study groups.

“The relationship of the gut microbiome and diet to neurodegenerative diseases has recently received considerable attention, and this study suggests that Alzheimer’s disease is associated with specific changes in gut bacteria and that a type of ketogenic Mediterranean diet can affect the microbiome in ways that could impact the development of dementia,” said Hariom Yadav, Ph.D., assistant professor of molecular medicine at Wake Forest School of Medicine.

The randomized, double-blind, single-site study involved 17 older adults, 11 diagnosed with MCI and six with normal cognition. These participants were randomly assigned to follow either the low-carbohydrate modified Mediterranean-ketogenic diet or a low-fat, higher carbohydrate diet for six weeks then, after a six week “washout” period, to switch to the other diet. Gut microbiome, fecal short chain fatty acids, and markers of Alzheimer’s in the cerebrospinal fluid were measured before and after each dieting period.

The limitations of the study included the subject’s group size, which also accountns for the lack of diversity in terms of gender, ethnicity, and age.

“Our findings provide important information that future interventional and clinical studies can be based on,” Yadav said. “Determining the specific role these gut microbiome signatures have in the progression of Alzheimer’s disease could lead to novel nutritional and therapeutic approaches that would be effective against the disease.”

Each human contains trillions of organisms that influence our metabolism, immune function, weight, and even cognitive health. It is so fascinating to examine the role of gut microbiomes in the progression of Alzheimer’s disease. I believe diets can be very controversial, and I find it interesting to see researchers in this study show how the Mediterranean-ketogenic diet may be effective against Alzheimer’s. However, I am so intrigued to see where these findings may take us with approaches that may be effective against Alzheimer’s, whether they be nutritional or therapeutic approaches.

How did butterflies evolve to eat poison?!

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On October 26, 2019

In Student Post

A recent article confirms that scientists have researched that caterpillars are now eating milkweed (which is supposed to kill them). How is this happening? “Scientists have unraveled the sequence of gene mutations that enabled the monarch butterfly to thrive on toxic milkweed.” We learn at a young age that caterpillars turn into beautiful butterflies, so something must be happening before metamorphosis. There are three gene changing mutation amino acid sites including, 111, 119, and 122. Mutation 122 had the biggest boost in resistance. Another article states that ‘monarch flies’ continue to have small amounts of cardiac glycosides through metamorphosis, which is a trait that has been developed in monarch butterflies to restrain predators.

Monarch butterfly eating milkweed

Monarch butterflies can eat milkweed due to a peculiarity in a crucial protein in their bodies, which is a sodium pump, that the cardenolide(steroid) toxins intervene with. How the pumps work? They move positively charged sodium atoms out of the cell resulting in the inside of the cell is negatively charged. In order for a heart to beat, the sodium pump has to build up enough electric charge and then nerves use the pumps to send signals to the brain.

Potassium pump diagram where the pump moves the sodium and potassium ions through the membrane

What does milkweed have to do with this? In the study, they first addressed how milkweed is toxic to almost all insects, but caterpillars depend on milkweed. Females use milkweed to lay eggs and caterpillars eat as much as they can before chrysalis. In the article, they are referred to as “flying poison” because the milkweed toxin gets send from their gut to their wings and anything that tries to eat it immediately vomits it up.  After these mutations, they now NEED milkweed to live and it altered the sodium pumps, so cardiac glycosides in the monarchs cells don’t affect them.

This mutation allowed butterflies to have their own food supply since milkweed is poisonous to other insects. Noah Whiteman, a biologist at the University of California, Berkely used CRISPR to try the mutations on fruit flies. The fruit fly experiment resulted in the findings that mutation 122 has bad side effects and is only useful if followed by another mutation. Other researchers say the order that mutations are done can make a big difference as well.

 

New anti-CRISPR Proteins Serving as Impediments to this Miraculous System.

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On March 17, 2019

In Student Post

CRISPR-Cas9 systems are bacterial immune systems that specifically target genomic sequences that in turn can enable the bacterium to fight off infecting phages. CRISPR stands for “clusters of regularly interspaced short palindromic repeats” and was  first demonstrated experimentally by Rodolphe Barrangou and a team of researchers at Danisco. Cas9 is a protein enzyme that is capable of cutting strands of DNA, associated with the specialized stretches of CRISPR DNA.

Diagram of the CRISPR prokaryotic antiviral defense mechanism.

Recently, a blockage to the systems was found by researchers which are essentially anti-CRISPR proteins. Before, research on these proteins had only showed that they can be used to reduce errors in certain genome editing. But now, according to Ruben Vazquez Uribe, Postdoc at the Novo Nordisk Foundation Center for Biosustainability (DTU), “We used a different approach that focused on anti-CRISPR functional activity rather than DNA sequence similarity. This approach enabled us to find anti-CRISPRs in bacteria that can’t necessarily be cultured or infected with phages. And the results are really exciting.” These genes were able to be discovered by DNA from four human faecal samples, two soil samples, one cow faecal sample and one pig faecal sample into a bacterial sample. In doing so, cells with anti-CRISPR genes would become resistant to an antibiotic while those without it would simply die. Further studies found 11 DNA fragments that stood against Cas9 and through this, researchers were ultimately able to identify 4 new anti-CRIPRS that “are present in bacteria found in multiple environments, for instance in bacteria living in insects’ gut, seawater and food,”  with each having different traits and properties.  “Today, most researchers using CRISPR-Cas9 have difficulties controlling the system and off-target activity. Therefore, anti-CRISPR systems are very important, because you want to be able to turn your system on and off to test the activity. Therefore, these new proteins could become very useful,” says Morten Sommer, Scientific Director and Professor at the Novo Nordisk Foundation Center for Biosustainability (DTU). Only time will tell what new, cool, and exciting discoveries will be made concerning this groundbreaking system! What else have you guys heard? Comment below!

Monkeys Cloned with CRISPR Technology

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On March 12, 2019

In Student Post

Chinese researchers used CRISPR technology to genetically edit macaque monkey embryos in order to create five monkeys with severe sleeping disorders by removing BMAL1, a gene important for circadian regulation. They then chose the monkey of the five with the most severe symptoms to clone as a model to use for future tests on monkeys with these disorders. The idea behind this research was to create a template to create clone monkeys with the disease to run tests on rather than the real monkeys themselves.

A large issue with this experiment was the ethics behind it. While the end result is to reduce the number of monkeys used in research experiments. According to the study, the disorder in the monkeys resulted in not only lack of sleep but also changes in blood hormones, increased anxiety and depression, and even “schizophrenia-like” behavior. Bioethicist Carolyn Neuhaus thinks the study is morally wrong because the monkeys are used as tools, and the research’s success is based on their suffering.

Image result for crispr

Genes

CRISPR used to Control Genetic Inheritance in Mice!

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On March 12, 2019

In Student Post

Scientists around the world have been using CRISPR/Cas9 in a variety of plant and animal species to edit genetic information. Although this has been tested recently on insects, it is currently moving towards testing mammals. It happens to be more difficult with mammals due to the longevity between generations. However, It’s been done!!

UC San Diego researchers have developed a new active genetic technology in mice. Graduate student Hannah Grunwald, Assistant Researcher Valentino Gantz and colleagues led by Assistant Professor Kimberly Cooper, layed the groundwork for further advances based on this technology, including biomedical research on human disease.Image result for mice

“To demonstrate feasibility in mice, the researchers engineered an active genetic “CopyCat” DNA element into the Tyrosinase gene that controls fur color. When the CopyCat element disrupts both copies of the gene in a mouse, fur that would have been black is instead white, an obvious readout of the success of their approach. The CopyCat element also was designed so that it cannot spread through a population on its own, in contrast with CRISPR/Cas9 “gene drive” systems in insects that were built on a similar underlying molecular mechanism.”

The project duration was two years, and the researchers used many ways to “determine that the CopyCat element could be copied from one chromosome to the other to repair a break in the DNA targeted by CRISPR”. Some gene that was originally existent on only one of the two chromosomes was copied to the other chromosome. They were able to convert one genotype from heterozygous to homozygous, and they were able to tell in that there were  as many as 86 percent of offspring that inherited the CopyCat element from the female parent instead of the usual 50 percent.

The test was successful for the female mice’s production of eggs, but not for the males production of sperm. The researchers predict this is a possibility to a difference in the timing of male and female meiosis.

As this test was only the beginning, researchers such as those at UC San Diego hope to soon move on to research on human disease. They say that “Future animal models may be possible of complex human genetic diseases, like arthritis and cancer, which are not currently possible.”, and with their hard work, their research can lead to miracles.

CRISPR Produce… the future of Food?

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On March 12, 2019

In Student Post

For years, people have been getting their food from, primarily, agricultural and cattle sectors; however, with CRISPR, everything is about to change. Or is it? Can CRISPR actually be used to make food in labs and completely change the way that the world receives their nourishment? These are questions that tech, scientists, and investor moguls have been asking for years, and Bill Gates’ new start up may have found the answer!  

Memphis meats, a new tech company that is backed two tech moguls, Bill Gates’ and Richard Branson, believes that they have found a new way to feed the world. The Memphis team have been successful in creating lab grown meat, using the CRISPR method. With their proprietary patented technique, Memphis meats could be changing the world. One may not understand how beneficial lab grown food would be. It would: save animals, lower the amount of water use (while raising the cattle), and be able to be made both healthier and tastier.

 

The company uses a special technique that allows them to manufacture skeletal muscle, that is edible, using cells from the poultry species Gallus gallus, and from the livestock species Bos Taurus. In addition, Memphis meats is also exploiting new and innovative ways to make their products better for the environment and public health, and more affordable, and in turn, scalable – mass produced. With all this great innovation and progress, Memphis Meats says that they are a long way from making a product that is ready for customers and consumers. However, the future of food and agriculture is promising.

What do you think? Could CRISPR and “lab meats” change the way that humans get their food? Only time will tell.

This article is by Jon Christian from Futurism. The research and technology is proprietary and patented and not for the public to see.

article: https://futurism.com/bill-gates-startup-crispr-lab-meat

Planet of the (CRISPR-Edited, Cloned) Apes

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On March 12, 2019

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Several months ago, scientists in China cloned five gene-edited macaque monkeys. The clones were made through the somatic cell nuclear transfer method (SCNT)—a process in which a viable embryo is created from a body cell and an egg cell—that was used to produce the first primate clones around a year ago. In this instance, however, the monkeys’ genomes were first edited using CRISPR-Cas9—a unique genome editing tool that enables geneticists to edit parts of the genome by removing, adding, or altering sections of the DNA sequence—to show symptoms of sleep disorders by eliminating BMAL1, one of the positive elements in the mammalian auto-regulatory TTFL, which is responsible for generating molecular circadian rhythms. The result? The monkeys exhibited a wide range of circadian disorder phenotypes, including elevated night-time locomotive activities, reduced sleep time, reduced circadian cycling of blood hormones, increased anxiety and depression, and other schizophrenia-like behaviors. 

File:Macaque Monkey (16787053847).jpg

Macaque Monkey

Naturally, the results of the investigation triggered much backlash. According to Carolyn Neuhaus of The Hastings Center, the researchers viewed the suffering of the monkeys as a triumph, and failed to consider the moral implications of their investigation. “It’s very clear that these monkeys are seen as tools,” she told Gizmodo, the latter publication writing in a similar sentiment, “Their experiment is a minefield of ethical quandaries—and makes you wonder whether the potential benefits to science are enough to warrant all of the harm to these monkeys”. 

Nevertheless, the researchers involved in the experiment remain firm in their support of the experiment—the goal of which was to produce genetically identical monkey models of disease for biomedical research—on both moral and scientific grounds. “We believe that this approach of cloning gene-edited monkeys could be used to generate a variety of monkey models for gene-based diseases, including many brain diseases, as well as immune and metabolic disorders and cancer,” stated Qiang Sun, one of the research paper’s authors and director of the Nonhuman Primate Research Facility at the Chinese Academy of Science’s Institute of Neuroscience in Shanghai. Moreover, Reuters reported, “Xinhua [the state news agency] said the program, supervised by the institute’s ethics panel, was in line with international ethical standards for animal research”. Time will tell, ultimately, if the results of their experiment prove consequential on a larger scale. 

Going into the Brain with CRISPR

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On March 12, 2019

In Student Post

CRISPR is a relatively new tool that allows the editing of genomes via cutting and editing through the Cas-9 protein. There are unlimited opportunities and potential with this tool, and scientists are seeing the capability of CRISPR on rat brains.

Despite the advances of CRISPR, it is still difficult to work on central nervous system. Yet, scientists are working on the expression of the genes of rats involved in learning and memory, plasticity, and neuronal development. This technique paves the way for researchers to probe genetic influences on brain health and disease in model organisms that more closely resemble human conditions.

CRISPR is important in the field of neuroscience because it helps scientists understand brain development and neurological diseases like Alzheimer’s.   According to Harvard, CRISPR is the perfect technology to figure out if disrupting certain genes causes neurological disorders like OCD and autism.

In my opinion, the first step of understanding CRISPR’s effects on the mind is to test it out on similar, but less developed brains like rat brains. I do believe that CRISPR is the future of medicine and understanding the brain further and I can’t wait to work with this incredible piece of technology.

 

 

 

A CRISPR Controversy

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On March 12, 2019

In Student Post

The Issue:

A recent article published by Grace Tsoi highlights the ongoing controversy regarding CRISPR, a new technology capable of editing DNA sequences, and thus genomes. Among those experimenting with CRISPR is Chinese researcher He Jiankui, notoriously nicknamed “China’s Dr. Frankenstein.” Many are critical of He Jiankui, as they deem his work with CRISPR — such as producing the world’s first gene-edited babies — inhumane and unethical. He Jiankui, however, argues that CRISPR has the potential to help “…millions of families with inherited diseases or exposure to infectious disease.”

Pictured above is He Jiankui, researcher and associate professor of the Southern University of Science and Technology’s Biology Department.

The Study:

In proving CRISPR’s potential, He Jiankui referenced an experiment in which he was able to produce two healthy twin girls by manipulating their genes, specifically making them resistant to HIV. He Jiankui had ultimate success with CRISPR technology, as the twins produced were not HIV positive, unlike their biological father. To learn more about the threat of HIV during contraception, click here. While He Jiankui expressed pride to his audience, stating, “For this specific case, I feel proud actually. I feel proudest because Mark [father of the twins] thought he had lost hope for life,” some audience members did not feel the excitement. Rather, his animated claims were met with intense criticism.

The Risks and Suspicions:

Given CRISPR’s potential, why are people so critical? Is CRISPR’s label “gene scissors” accurate or oversimplified? Regardless of these answers, it is undeniable that utilizing CRISPR for human embryos is a much more complex process. As Kenneth Lee, a biomedical sciences professor at the Chinese University of Hong Kong, explains it, using CRISPR in human embryos is “highly risky,” and could potentially mutate other genes in the process. As a result, the embryo might not survive, or could acquire deformities and/or other genetic disorders. Adding another element to the audience’s suspicion of He Jiankui’s experiment was the secrecy surrounding it, as he failed to answer why he initially hid it from Chinese officials. Failing to consider the opinions of these aforementioned officials has left many questioning the genuine ethics of He Jiankui’s experiment. In defending his work, He Jiankui emphasized that every individual involved consented to his experiment and were well-educated on the study itself. However, the consent form uploaded to his website, explicitly states that He Jiankui would not be held responsible for any unintended gene mutation. Moreover, the University where he conducted his experiment appeared unaware of his lab work, thus rendering an investigation of He Jiankui’s activities. Although China is a more “relaxed” country regarding its gene editing rules (gene editing is banned in the U.S., as well as many other countries), He Jiankui has faced condemnation from many Chinese scientists. Despite this, he plans to expand his studies, focusing next on another gene-edited pregnancy — yet another controversial experiment that will prove to either have potential or deep ramifications. 

CRISPRi Antibiotics: Will Pathogens Cease to Exist?

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On March 12, 2019

In Student Post

Recently, a researcher at the University of Wisconsin-Madison and his collaborators at the University of California, San Francisco have discovered a way to repurpose CRISPR, a gene-editing tool, to develop new antibiotics.

What does this mean?

It is known that many disease-causing pathogens are resistant to current antibiotics. This new technique, Mobile-CRISPRi, is helping to change that. Mobile-CRISPRi allows scientists to “screen for antibiotic function in a wide range of pathogenic bacteria.” Scientists used of bacterial sex to transfer Mobile-CRISPRi from laboratory strains into any diverse bacteria. This easily transferred technique will now allow scientists to to study any bacteria that cause disease or help one’s health.

To break it down, Mobile-CRISPRi “reduces the production of protein, from targeted genes, allowing researchers to identify how antibiotics inhibit the growth of pathogens.” This will allow researchers to more thoroughly understand different bacterias’ resistance to current antibiotics.

Unlike CRISPR, which can split DNA into two halves, CRISPRi is a defanged form that is unable to cut DNA. Instead, it stays on top of the DNA, blocking other proteins from being able to turn on a specific gene.

Genes (DNA)

Why is this important?

It has been proved that a decrease in the amount of protein targeted by an antibiotic will make bacteria become more sensitive to lower amounts of that same antibiotic. This evidence association between “gene and drug” has allowed scientists to “screen thousands of genes at a time,” as they try to gain more knowledge about the mechanisms of how antibiotics work in organisms to improve those on the market now.

In order to study how antibiotics directly work in pathogens, researchers needed to make this CRISPRi mobile, or easily transferred onto different bacterias. There were two tests done to test CRISPRi’s mobility using conjugation. One involving a transfer of CRISPRi to the pathogens Pseudomonas, Salmonella, Staphylococcus, Listeria, and others, and another involving the bacteria that grows on cheese.

Science Daily describes the “landscapes of microbes cheese creates as it ages.” A bacteria called “Vibrio casei” was found on a French cheese in a lab back in 2010. With bacteria that have been taken out of their environment, it is hard to manipulate and study said pathogen’s genes, like “Vibrio casei.”

However, the mobile-CRISPRi was able to easily transfer onto the strain of  Vibrio casei that was discovered back in 2010. This has given scientists a new way of understanding how bacteria colonizes and ages cheese.

Peters, the head researcher of mobile-CRISPRi is generous enough to offer this system to other scientists who would like to study other germs. With this technology being available to others, scientists could potentially see first-hand how antibiotics work in pathogens, and use that information to improve those that currently exist, hopefully getting rid of these bacterias like pseudomonas, or listeria before they kill the human they are inside of.

The Collateral Damage of CRISPR-Cas9

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On March 12, 2019

In Student Post

 

CRISPR’s ‘precise’ gene-editing has actually been damaging other parts of the DNA sequence, according to a recent study. Photo from this source.

Of the various gene-editing techniques, CRISPR-Cas9 is the fastest, simplest, and most accurate gene-altering method known to date. Comprised of simply two parts, CRISPR-Cas9 snips through targeted segments of DNA and causes a change in the genetic code. Scientists are hopeful that we can soon use this method to cut out mutations that code for HIV, cancer, and sickle cell disease. However, a study published in Nature Biotechnology has revealed an unwanted side-effect of CRISPR.

When using CRISPR-Cas9, there are two major molecules that create a mutation, or change, in a DNA segment. The first is an enzyme called Cas9. This enzyme works like a pair of scissors and that cuts the two helices at a specific location so DNA can be altered. The second tool used in this process is the guide RNA (gRNA) that binds to the DNA and ensures that the Cas9 molecule cuts the DNA in the correct place. Finally, after the incision, the DNA will seal itself back together, without a trace of the deleted segment.

Such a precise process seems flawless. In theory, one should be able to cut out the unwanted genetic material and our DNA should perfectly repair itself. Unfortunately, senior group leader and director of the study at Wellcome Sanger Institute in England, Allan Bradley, stated that “CRISPR is not as safe as we thought.” Through a systematic and tedious approach, Bradley and his colleagues edited a series of mouse and human cells with CRISPR and then examined DNA base pairs father and farther away from the cut site. By examining millions of base pairs, the team landed upon unsettling news.

Bradley and his team found that huge chunks of DNA were inadvertently deleted, mutated, and rearranged millions of base pairs away from the cut site. The DNA was mutated so immensely that cells lost function in 15% of cases. Because these CRISPR-induced mutations were shown so far away from the cut site, this information could have easily been overlooked in other studies.  

This research poses questions on the accuracy of such gene-editing methods. What are the long-term effects of genetic engineering with CRISPR? How can we ensure that base pairs so far away from the cut site aren’t altered? Although this is somewhat discouraging news for the CRISPR community, this newfound information is motivating more researchers to improve CRISPR technology before making it widely accessible.

Read the full article here.

Let’s Talk About Malaria

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On March 12, 2019

In Student Post

Let’s Talk About Malaria

A small mosquito landing on a human finger.

 

Did you know, that the World Health Organization estimates that roughly 438,000 people die annually due to Malaria? Well, now you do know that unfortunate fact. But – did you know that the total number of people affected by malaria is only growing? In reality, those don’t matter, what does matter is what we are going to do now to combat the issue and CRISPR/cas9 might be the answer. In order to better understand the issue of Malaria and the resolution of utilizing CRISPR/cas9, let’s take an indepth look at both with the assistance of the article about Gene Editing to end Malaria from Vox.

 

So, what is Malaria? According to the Center for Disease Control, Malaria is a mosquito-borne disease caused by a parasite. The four kinds of malaria parasites that infect humans are Plasmodium falciparum, P. vivax, P. ovale, and P. malariae. Typical symptoms causes people to experience fever, chills, and flu-like illness. Left untreated, they may develop severe complications and die. Basically, Malaria has been affecting the global population for decades.  Now, you might be asking yourself: then, what is CRISPR/cas9? Fantastic Question! According to the National Institute of Health, CRISPR/cas9 is recent biomedical technology phenomenon that is drastically changing the genome editing space. In specifically, CRISPR/cas9, which is short for clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9, has generated a lot of excitement in the scientific community because it is faster, cheaper, more accurate, and more efficient than other existing genome editing methods.

 

So, here is the big question: why does it matter? Here is why it matters. When looking at Anopheles Gambiae Mosquito larvae, a common carrier of the Malaria parasite, in a lab in the United Kingdom, a couple of researchers noticed that all of the larvae had a physical red fluorescent phenotype. Although this doesn’t sound shocking, this is extremely shocking as only one parent had the red fluorescent recessive genotype and the other had the dominant wild type, so the expected offspring would be fifty percent with the red fluorescent gene and fifty percent without the red fluorescent gene, but all of the Mosquitos had the red fluorescent gene. This gene has been linked on Mosquitos to the fertility of female mosquitos. Now, you might be asking yourself: when does CRISPR/cas9 come into play? Well, CRISPR/cas9 can target and locate a specific gene, cut, enter itself in and then passed onto the abundant and constant offspring. As a result, when the CRISPR/cas9 is utilized to alter the mosquito population to be resilient to the Malaria parasite and could “wipe” Malaria from the future history of the planet.

 

In reality, I could never say that this is bad thing as it is working to save lives of hundreds of thousands of people globally. As a matter of fact, I would believe the majority of the population would say this is a good thing, but I am going to say this: do it, but do it right. This is something that needs to be done, Malaria has wreaked havoc on our global community for decades and we must move past that, but any small mistake would halt progress in this field for year. In conclusion, let’s keep having a serious discussion on changing the status of Malaria globally.

 

Thank you!

 

From your favorite bacteria,

SAMonella

 

CRISPR/Cas9: A New Means to Alter Genes

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On March 12, 2019

In Student Post

Biologists can now control genetic inheritance in mammals with a CRISPR/Cas9-based approach, which allows geneticists to alter parts of the genome by removing, adding or altering sections of the DNA sequence.  Scientists have sought a way to make precise changes to the genome of living cells for a long time, and now they actually can. You may ask, what are CRISPR and CAS9? Why are they important? Simply put, “The functions of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and CRISPR-associated (Cas) genes are essential in adaptive immunity in select bacteria and archaea, enabling the organisms to respond to and eliminate invading genetic material.”  Thus, this recent discovery has created the groundwork for developing new ways to fight diseases. UC San Diego researchers are responsible for this breakthrough. First, they injected a mouse with an engineered active genetic “CopyCat” DNA element into a Tyroisinase gene. The Tyroisinase gene determines fur color. The CopyCat element “disrupts” both copies of the Tyroisinase gene, causing the mouse to have white fur instead of black. The CopyCat element, however, could not spread through a population by itself, unlike the CRISPR/Cas9 systems, which could. This approach, though, was effective only in female mice, not in male ones, likely because of timing differences in meiosis – “a process that normally pairs chromosomes to shuffle the genome and may assist this engineered copying event.” The findings are nonetheless a success. Scientists are optimistic they will be able to alter multiple genes and traits using the same techniques in the near future. Cooper, one of the researches, summed up their achievement nicely: “We’ve shown that we can convert one genotype from heterozygous to homozygous. Now we want to see if we can efficiently control the inheritance of three genes in an animal. If this can be implemented for multiple genes at once, it could revolutionize mouse genetics,” said Cooper. More importantly, these findings continue to speed up research into diseases like cancer and mental illness.

Related image

CRISPR-CAS9 — “How the genome editor works”

CRISPR in the Modern World

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On March 12, 2019

In Student Post

Shawna William’s article “Crispr Babies Trial May Have Been Government Funded” on The Scientist speaks about how the most recent update on the Chinese experiment with Crispr. Scientist He Jiankui and his team came out with the new information that his experiment, which used CRISPR on the embryos of two twin girls, was funded by the government of Guangdong Province. CRISPR uses enzymes from bacteria to “edit” (aka alter) genomes of organisms to correct mutations. This technology is groundbreaking as it can be used to control the DNA of future generations. This article, in particular, focuses on the crucial point that this new information contradicts the findings of the government’s own investigation along Jiankui’s previous claims and then proceeds to evaluate all parts of this experiment.

        MIT Technology Review and the Associated Press reported in November that He modified the CCR5 gene in embryos in order to ensure that the children will be immune to HIV. One neurobiologist, Alcino Silva believes that this altering this gene has impacted the CRISPR babies and their ability to recover from strokes and better cognition, while others like geneticist Gaetan Burgio of the Australian National University believe that this study is completely wrong. Considering Burgio disputed this study over twitter instead of using a more valid outlet through publications like The Scientist, I personally do not believe that his dispute of Silva’s claim is valid. Moreover, I believe that it is extremely important that further investigation of whether the Chinese government was involved must continue. If it can be proven that the government funded this research, I truly believe that worldwide bureaucratic branches must become involved in order to reinforce that the Chinese government must uphold science ethics. Although this new tool will definitely be used to benefit the  Experiments like He’s can be detrimental to everyone involved.  

Gene Editing in Butterflies: What Could This Mean for Their Mating Patterns ?

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On March 12, 2019

In Student Post

The beautiful Heliconius butterflies from Central and South Africa are known for their colorful wing patterns. Some of their wing patterns mimic that of other species to protect them from their predators. There is one species of these evolutionary marvels, Heliconius cydno, that scientists have found that the activation of a single gene can determine whether the butterfly expresses white or yellow spots. To come to this conclusion scientists created a genetic map of H.cydno with both white and yellow coloring.

Through examining the genetic maps, the researchers found that the gene al1 was switched on in the white colored butterflies which would mean that al1 gene was correlated to the production of yellow pigmentation. To test this the researchers used CRISPR (a gene editing tool) to switch off the al1 gene in what was supposed to be white spotted butterfly embryo. They found that by switching off that gene the butterflies developed with yellow spots.

The researchers that carried out this experiment also looked into the evolutionary history of these butterflies since this experiment didn’t add pigmentation to the butterflies but changed an ancestrally present pigment by switching off a gene through CRISPR. They studied the al1 gene to butterflies that are closely related to the Heliconius species and found that white version of the spots is a recent development and that H.cyndo was first species to develop the white spots.

After further examination, there was evidence that the white version of the spots corresponds to matting patterns. So, the white spotted H.cydno males preferred to mate with the white spotted H.cyndo females and vise versa with the yellow spotted H.cydno males to H.cydno females. Which begs the question of what roles does the activation of al1 play in not only the coloration of these butterflies but also evolutionarily going forward? If gene activation through CRISPR continues how will that also affect the future mating patterns of these butterflies but possible of other species too?

Cute Pigs Save the Day

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On March 12, 2019

In Student Post

Here, we might see two cute pigs having a lovely time, but biologist Luhan Yang sees otherwise; she sees life-saving organs!

With her remarkable Harvard background in genome-editing and bioengineering, Luhan Yang plans to use CRISPR to create pigs whose organs can be transplanted into people.

With miracles come challenges, which Luhan Yang faces a lot of! Luhan Yang is putting in front of herself the challenging of CRISPR’ing an unprecedented number of genes without being sure of the outcome. There is also the issue of money that needs to be raised.

Astonishingly, in 2015, Luhan Yang and her colleagues used CRISPR to eliminate 62 genes from pig cells that would have been dangerous they had been transplanted into humans. In March of 2017, Luhan Yang and her company, eGenesis, have raised $38 million from investors. These milestones have led Luhan Yang and her team to approach a new step where they get a surrogate mother that becomes pregnant with genetically altered embryos.

As successful as this idea sounds, Luhan Yang and her research team have stumbled upon many problems. One of them being the PERV genes that are interwoven into the genome of pig cells. In order to remove these genes though, the team uses CRISP-Cas9 to remove these genes. With these newly-edited cells, eGenesis ships many of these cells to China where each de-PERV’ed pig cell is fused with a pig ovum whose own DNA has been removed; this ova now contains solely the PERV-free genome. Unfortunately, all has not gone well as there have unfortunately been a lot of miscarriages and not all of the PERV-genes have been removed. Regardless of these setbacks, Luhan Yang is confident that she will make progress with her ideas and will push the limit of genomic technology.

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