BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: genetic engineering

The “Most Complicated” Cancer Treatment EVER

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On April 23, 2023

In Student Post

There are many approaches to treating cancer, ranging from invasive surgeries to extremely damaging radiation and chemotherapy.  The teeny-tiniest clinical trial ever began at UCLA in yet another attempt to find another way to eradicate cancer.  With only 16 participants, this trial combined two areas of research: gene editing and T-cell engineering.   The reason for the miniscule sample size is the intensely customized nature of the treatment.  Each patient’s tumor had completely unique mutations, so each patient needed equally unique T-cell engineering through gene editing.  

One reason cancer is so hard to treat is because they have adapted to be resistant to the body’s own immune response.  The patients that have cancers, especially ones in the later stages, have lost the battle against their cancer with their own immune system, so a new super-immune system must now be built.  This army of new T-cells (white blood cells, which identify and kill bad cells, seen below) will need “training” for its difficult battle ahead.  First, however, the researchers must determine how to train these cells so they will actually be successful.  They used algorithms to find identifiable mutations in the tumor, something that the T-cell can seek out to differentiate the cancerous cells from the normal cells.  Healthy Human T Cell

After testing to make sure that the T-cells can actually identify these mutations, T-cell receptors are designed specifically to their tumor.  Then, each patient’s blood is taken so that the DNA code for the new receptors can be inserted using CRISPR,  a genome editing technology at the cutting edge of genetic medical research.  The DNA code is transcribed to mRNA, which is then used in the ribosome to build polypeptides, in this case, the receptor proteins for the T-cells.  In order to ensure that these new T-cells (with the special receptors) are received, the patients had to take medication that suppressed the number of immune cells, so that the ones they are given can take hold.  

One month into treatment, 5 of the patients’ tumors stopped growing, and only 2 of the participants had associated side effects.  Although only 5 patients had the desired results, Dr. Ribas, one of the researchers, says that they “need to hit it stronger the next time” because they were limited to a small dosage of T-cells to start in order to establish safety.  Additionally, the technology will only get better and better as the research progresses and the T-cells can have more and more mutation targets to look for in a tumor.  

Genetically engineering the microbiome

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On November 19, 2018

In Student Post

Researchers from Harvard University have successfully taken the first steps in creating a synthetic microbiome. Using signaling between Salmonella Typhimurium and E. coli, the team was able to promote a new “genetic signal-transmission system” in mice.

A cluster of E. coli, a common species of gut bacteria.

With the hope of inducing interspecies bacterial communication, the researchers manipulated the bacterial signaling method of quorum sensing where bacteria receive and send signaling molecules in order to gauge their population density, performing a group behavior after reaching a certain threshold. By using the variant acyl-HSL quorum sensing, a version absent in mammals, the researchers were able to assess the feasibility of using a signaling system nonnative to its host.

In order to see if the two bacterial species successfully communicated, the researchers introduced both a signaler circuit and a responder circuit into the mice. The signaler circuit, put into Salmonella Typhimurium, contained a gene called luxI that, when turned on by a molecule called ATC, produced a quorum signaling molecule. This molecule was received by the bacteria with the responder circuit, E. coli, triggering a cro gene. This gene then turned on a LacZ gene, which caused the bacteria to turn blue when plated with special agar, and another cro gene, creating a loop that continuously activated the LacZ gene. This served as an indicator, as a blue glow would illustrate if the interspecies communication and the E.coli’s “memory” of it were successful.

After the mice were given the two edited strains of bacteria and placed in a container with ATC-infused water for two days, the researchers analyzed their fecal samples. They found that all of them turned blue, indicating that the genetically engineered signaling system was successful: the E. coli received and remembered a signal from Salmonella Typhimurium in response to an environmental factor. This effective engineered communication, as the Director of Harvard’s Wyss Institute for Biologically Inspired Engineering puts it, is a major step forward in “engineer[ing] intestinal microbes for the better while appreciating that they function as part of a complex community”.

With the basic principles of a synthetic microbiome a success, the researchers now want to experiment with new bacterial species and signaling molecules, bringing them closer towards their ultimate goal of engineering a gut microbiome that can perform tasks ranging from improving digestion to curing diseases. As the “next frontier in medicine [and] wellness,” the microbiome will no doubt be a key pillar of medicinal research for decades to come.

Genetic Engineering on Gut Bacteria!?

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On November 10, 2018

In Student Post

E. coli on MAC – Photo credit to VeeDunn on flickr under Creative Commons License

Researchers at the Wyss Institute at Harvard University has successfully tested a genetically engineered signaling bacteria within a mouse’s gut. Having known that the many types of bacteria in the human gut can communicate through “quorum sensing” , researchers set to observe a particular type of quorum sensing, acyl-homoserine lactone sensing, which has not been observed in the mammalian gut. They wanted to test if using that particular type of signaling could create a genetically engineered bacterial information transfer system.

Using a strain of E. coli bacteria, they created two different colonies, each with a different genetic change: one was the “signaler”, it contained a copy of the luxl gene which produces a quorum-sensing molecule when activated, and the other was the “responder”, which contained a “cro” gene turning on a “memory element” in the responder.  This “memory element” expressed another copy the the pro gene, which allowed for the loop to continue, and the LacZ gene, which made the bacteria turn blue!

LacZ gene expression – Photo credit to Viraltonic on Wikimedia Commons under Creative Commons License

The researchers analyzed fecal samples of mice given signaler and responder E.coli and they were happy to see the signal transmission, blue coloring, was evident in the samples. This result meant that they had created a functional communication bacteria system in the mouse’s gut.

The researchers then repeated their experiment with a different type of bacteria, S. Typhimurium, as the “signaler” and E. coli as the “responder”, and they were pleased to see similar successful results.  They were able to successfully confirm that is possible to genetically engineer these communication circuits between different species of bacteria in the mammalian gut microbiome.

These tests are merely stepping stones for the bigger goal of creating genetically modified bacteria that will help humans in various different ways: detecting and or curing diseases, improving digestion, and so on. Isn’t it cool that something we barely realize is inside us has such a developed communication system that we might soon be able to cultivate more benefits from? What do you think would be some other benefits to be being able to genetically modify our gut microbiomes?

 

 

Genetic Engineering will Create Super Humans?!

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On November 8, 2018

In Student Post

“Synthetic microbiome? Genetic engineering allows different species of bacteria to communicate”

Before seeking to analyze how genetic engineering enables the alteration of the microbiome, it is essential to understand the nature of the microbiome. Humans’ microbiomes consist of “trillions of microorganisms (also called microbiota or microbes) of thousands of different species.” Initially, peoples’ microbiomes are solely determined by their DNA; however, as time goes on, a person’s microbiome can be shaped by other factors, including the environment in which they live, or their diet. The microbiome contains both helpful and deleterious microbes, but “In a healthy body, pathogenic and symbiotic microbiata coexist without problem.”

According to researchers from the Wyss Institute at Harvard University, Harvard Medical School (HMS), and Brigham and Women’s Hospital, it may now be possible to create a “synthetic microbiome.” The team did a study in which they utilized a particular type of quorum sensing known as acyl-homoserine lactone sensing. Quorum sensing allows bacteria to regulate the expression of genes and to detect the size of bacterial colonies, through signal molecules. First, the team inserted “two new genetic circuits into different colonies of a strain of E. coli bacteria.” One of the circuits acted as a “signaler” and the other acted as a “responder.”

File:E. coli Bacteria (16578744517).jpg Picture of E. Coli bacteria

In short, the team inserted a single copy of luxl, a gene activated by the molecule anhydrotetracycline (ATC), into the signaling circuit. The signaling molecule formed by this gene then binded to the receptor circuit, which activated another gene, known as cro. The cro gene creates Cro proteins, and these proteins triggered a “memory element” within the responder circuit, in which two more genes, LacZ and another cro, were produced. If the signaling molecule is received (which it was), the presence of LacZ causes the bacterium to turn blue. Most importantly, the additional cro gene essentially keeps the “memory element” on, so this cycle continues.

To make sure that this system works in living organisms, the researchers tested it in mice. Signs of signal transmission in the mouse’s gut between the signaler S. Typhimurium bacteria and E. coli responder bacteria were detected. In other words, the engineered circuits allowed the bacteria to communicate with one another.

While these findings are extremely exciting, scientists have yet to discover whether or not other genetically engineered species of bacteria will also be able to facilitate communication between molecules. A Founding Core Faculty member of the Wyss Institute said that “[They] aim to create a synthetic microbiome with completely or mostly engineered bacteria species in our gut, each of which has a specialized function.” If this is achieved, we will move one step closer to becoming super humans!

Feature Image: “Free for Commercial Use” and “No attribution required”

Crispr-Cas9 is the gateway to a new frontier in genetic engineering. Here’s The good and the bad.

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On March 13, 2018

In Student Post

For a number of years now, molecular biologists have been diving increasingly further into the field of genome editing. The latest development into the field is the emergence of CRISPR-Cas9. CRISPR-Cas9 has risen to prominence over other potential methods of genome editing due to its relatively simple construction and low cost. CRISPR-Cas9’s original primary and intended purpose was to help fix mutations within DNA, and with this it could theoretically help eradicate entire diseases. This application of CRISPR is wholly positive, however with the increasing prevalence of the technique other potential uses have been discovered, and some of these potential uses raise profound ethical questions.

One of the main concerns of people skeptical about CRISPR is their assertion that once the door to the wholesale genetic editing of offspring is open, there is no going back. This, on its own, is a reasonable concern. The ability to choose a child’s sex, eye color, hair color and skin complexion is very likely to be made available to by CRISPR in the coming years. CRISPR does not yet have the capability to influence more abstract elements of the genome, such as intelligence and athletic ability, but this may not be far off. There are legitimate concerns that this is a slippery slope towards a dystopian society similar to the one seen in the movie Gattaca, where society is stratified into two distinct classes: those who are genetically engineered and those who are not.

Another concern raised by some scientists is the overall safety of genetic editing. A potentially very hazardous negative result of CRISPR is the possibility of an “off target mutation.” An off target mutation is the result of CRISPR mutating something other than the intended part of the genome and it could have disastrous consequences. Now, many scientists believe that with further advancements in the field the likelihood of something like an off target mutation occurring could be reduced to almost zero. However, it is important to examine the risks of any new process, and the prospect of something like an off target mutation occurring is certainly noteworthy.

For more information click here.

CRISPR Cas9: A Pathway for Designer Babies?

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On March 7, 2018

In Student Post

Can embryo modification allow parents to “custom order a baby with Lin-Manuel Miranda’s imagination or Usain Bolt’s speed?”

https://www.pexels.com/photo/adorable-baby-baby-feet-beautiful-266011/

Within the past decade, there has been an explosion in the use of CRISPR-Cas9, a gene editing tool that allows scientists to edit parts of the genome by removing, adding, or altering sections of the DNA sequence, in science research. Yet the promising technology renews the ethical issues rooted in genetic engineering and brings up the question: of what practices and ideas could become a reality in the near future? What about designer babies– embryos that have been genetically modified to produce desirable traits, such as greater athletics or higher intelligence?

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Gene Therapy Saves the Life of Dying Boy with Genetic Skin Disease

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On December 10, 2017

In Student Post

A 7-year-old boy with a rare genetic skin disease is reported to have made significant progress after eighty percent of his skin has been replaced through gene therapy. The boy, Hassan, was diagnosed a severe genetic disease called Junctional Epidermolysis Bullosa (EB) that destroyed most of his skin. Caused by a mutation in a gene encoding part of the protein Laminin 332, EB causes fragile skin that blisters and tears even with the slightest touch and is prone to infections and skin cancer.

When Hassan contracted a bacterial infection and lost two-thirds of his skin, doctors struggled to find a way to save the boy. Trying antibiotics, bandages, special nutritional, skin transplant from his father, nothing seemed to work, and after two months, doctors were sure they could not save him and thought that “he would die”.

https://commons.wikimedia.org/wiki/File:Stem_Cell_Research_(0449)_(14001969013).jpg

Doctors then reached out to Dr. Michele De Luca, the director of the Center for Regenerative Medicine Stefano Ferrari at the University of Modena and Reggio Emilia in Modena, Italy and who had treated smaller patches of skin on patients with EB. Dr. Michele De Luca and his team experimentally extracted a sample of approximately half a square inch of the boy’s skin, genetically engineered the cells by using a virus to replace the mutated gene with a normal version in the DNA. In the laboratory, the new skin cells were grown into sheets of skin, which was then grafted by surgeons back onto the boy’s body.

By the end of the procedure, the doctors had replaced nine square feet or eighty percent of Hassan’s skin– the greatest surface area covered in a patient with the genetic disorder. As the surgery was a success, Dr. De Luca notes about Hassan, “when he woke up, he realized he had a new skin.”

The success of the project and surgery is “one of these [studies] that can determine where the future of the field is going to go,” states physician Jakub Tolar. This study can also potentially help researchers use stem cells to treat other genetic skin conditions. As researchers continue to search for further advances in the field, Hassan is now happily able to play soccer and run!

Scientists Edit a Mutation from Genes in Human Embryos

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On October 11, 2017

In Student Post

https://upload.wikimedia.org/wikipedia/commons/6/6b/Embryo%2C_8_cells.jpg

Did you know that there are over six thousand genetic disorders? Have you ever wondered whether it was possible to prevent or “cure” a genetic disorder? Well, for the first time in history, a group of scientists have succeeded in editing a dangerous disease-causing mutation out of human embryos.

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Genetically Modified Food? Now You Can Know For Sure.

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On March 10, 2013

In Student Post

Whole Foods Market has officially become the first grocery store to require the labeling of all genetically modified foods. In an article published by The New York Times, on Friday, March 8th, Whole Foods Market announced that they will be labeling all genetically enhanced food products.

According to Whole Foods president A. C. Gallo, the new labeling requirement was implemente due to consumer demand. Mr. Gallo stated that that their “manufacturers say they’ve seen a 15 percent increase in sales of products they have labeled.”

Today, genetically modified foods are of great abundance in the global food supply. For example, most of the corn and soybeans grown here in the United States are genetically altered. The alterations make the soybeans resistant to a herbicide used in weed control, and causes the corn to produce its own insecticide. Scientists are currently working on producing a genetically modified apple that will spoil less quickly, and genetically modified salmon that will grow faster.

What do you guys think of the position Whole Foods is taking with labeling their products? What are your thoughts on genetically modified food in general? Do you believe that genetically modified foods are safe for humans to consume? Please leave your thoughts and comments below.

 

Quarter Horse? More like Million Dollar Horse! But is it all worth it?

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On February 27, 2012

In Student Post


According to the article, “How the Quarter Horse won the Rodeo” , quarter horses are known for their superior speed, agility, and tranquility.   Why are these horses so superior? According to BioMed Central’s open access journal, BMC Genomics, used sequencing to map variation in the genome of the quarter horse male. The sequencing revealed that the quarter horse’s genome was enriched for variants in genes involving sensory perception, signal transduction and the immune system.  Further research was done on the genetic variants of these horses by the researchers from Texas A&M University. The researchers evaluated genetic variants in quarter horses such as single nucleotide polymorphisms (SNP), copy number variants (CNV), and insertions and deletions (INDELs).

Not only do these variants help explain the uniqueness and superiority of these horses, but they have also been of use to equine breeders and veterinary medicine to improve the health and performance of these horses. For example, these variants can be used to fix HERDA, a disease in which the skin of the quarter horses is fragile and thus tears easily. So, in the spirit of the film GATTACA and the ethics of genetic engineering, what are your feelings on using these variants to enhance these quarter horses? And what about enhancing humans?

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