BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: geneediting

From Bacteria to Biotech: The Surprising Similarities in Immune Systems

Bacteria have always been considered harmful and something to be avoided, but according to a recent study by the University of Colorado Boulder, bacteria might just hold the key to unlocking novel approaches to treating various human diseases. The research reveals that bacteria and human cells possess the same core machinery required to switch immune pathways on and off, meaning that studying bacterial processes could provide valuable insights into the human body’s workings. Moreover, researchers found that bacteria use ubiquitin transferases – a cluster of enzymes – to help cGAS (cyclic GMP-AMP synthase) defend the cell from viral attack. Understanding and reprogramming this machine could pave the way for treating various human diseases such as Parkinson’s and autoimmune disorders.

CRISPR, a gene-editing tool, won the Nobel Prize in 2020 for repurposing an obscure system bacteria used to fight off their own viruses. This system’s buzz reignited scientific interest in the role proteins and enzymes play in anti-phage immune response. Aaron Whiteley, senior author and assistant professor in the Department of Biochemistry, said that the potential of this discovery is much bigger than CRISPR. The team discovered two key components, Cap2 and Cap3 (CD-NTase-associated protein 2 and 3), which serve as on and off switches for the cGAS response. Understanding how this machine works and identifying specific components could allow scientists to program the off switch to edit out problem proteins and treat diseases in humans.

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This discovery opens new avenues of research as bacteria are easier to genetically manipulate and study than human cells. Whiteley said that the more scientists understand about ubiquitin transferases and how they evolved, the better equipped the scientific community is to target these proteins therapeutically. The study provides clear evidence that the machines in the human body that are important for just maintaining the cell started out in bacteria, doing some really exciting things. The ubiquitin transferases in bacteria are a missing link in our understanding of the evolutionary history of these proteins. Thus, this research shows the importance of studying evolutionary biology, and how it can provide valuable insights into human health.

The study highlights the similarities between bacteria and human cells in terms of their immune response, specifically, describing how cGAS (cyclic GMP-AMP synthase), a protein critical for mounting a downstream defense when the cell senses a viral invader, is present in both bacteria and humans. This similarity suggests that portions of the human immune system may have originated in bacteria, a concept explored in the evolutionary biology unit. In this past unit, we discussed the origins of life, and how all life originated from a simple bacteria cell. This bacteria cell, though many many many repeated cycles of evolution and natural selection allowed for variation within its species and the formation of new species through the processes of speciation.

CRISPR gene editing: The Benefits and the risks

CRISPR gene editing is a precise technique that uses the Cas9 enzyme and gRNA to modify DNA sequences in an organism’s genome. This method is inspired by a natural bacterial mechanism that protects against viruses. It can change existing genes, introduce new genetic material, and revolutionize fields such as industry, agriculture, and medicine.

CRISPR gene editing was first invented in 1987 by Ishino Etal. Scientists first hypothesized that prokaryotic cells use this method as part of their adaptive immune systems. However, this method was not elucidated until 2007. This gene-editing technique uses RNA molecules to direct the Cas9 enzyme to the precise location where the DNA strands are being cut, thus allowing genetic materials to be modified or added. To be more specific, this system relies on the enzyme’s ability to cleave DNA double helix strands at a particular location, allowing scientists to modify the DNA sequence. This technique is especially beneficial to the medicinal fields due to its specificity; it can potentially treat genetic diseases such as cystic fibrosis, Alzheimer’s, Huntington’s, Parkinson’s, or cancer by modifying the immune cells and directing them to target and kill cancer cells.

CRISPR-Cas9 Editing of the Genome (26453307604)

Despite the benefits, CRISPR also contains some serious risks. A specific protein called p53, also known as the “guardian of the genome,” helps to detect any damage in the DNA and thus; heads the cells to stop diving to prevent any mistakes. The CRISPR technique might trigger a p53 response, in which edited cells can be “tagged” as damaged and eliminated, thus reducing the efficiency of the gene editing process. However, recent research also indicates that CRISPR can lead to cell toxicity and genome instability. In addition, CRISPR may disrupt normal cell functioning, which leads to cells being unable to detect any DNA damage or extra cell division, thus increasing the risk of further mutations.

Nonetheless, CRISPR still goes deep down into our biology field as it contains molecular biology, where it goes deep down into the cells and modifies DNA sequence. However, changing an organism’s DNA sequence using CRISPR gene-editing technology could have unintended consequences such as off-target effects, incomplete editing, and unknown long-term effects such as cancer or DNA mutation if the matching went wrong.

CRISPR Technology leads the way for potential breakthrough in cancer treatment

According to The American Cancer Society, scientists can alter the structure of a particular white blood cell known as the T-cell.  This method, known as CAR T-cell therapy, has long been established as a potential weapon against cancer, altering T-cells to best fight cancer based on the patient’s own characteristics.  According to an article in Forbes, the genetic editing procedure that has been used to facilitate this technology has relied upon “Viral Vectors,” which according to Beckman Coulter, viral vectors are modified viruses “that can be used to deliver nucleic acids into the genetic makeup of cells.”  While useful, Forbes asserts that the usage of Viral Vectors can be time-consuming and “can cost up to $50,000 per dose.”  For these reasons, scientists have looked towards a new technology, known as CRISPR technology to facilitate the editing of T-cells.CRISPR logo

 

According to the National Human Genome Research Institute, “CRISPR (short for “clustered regulatory interspaced short palindromic repeats”) is a technology that research scientists use to selectively modify the DNA of living organisms.”  According to Forbes, this technology differs from viral vector technology in that it involves the synthesis of “RNA guides,” which allow the scientists to break a DNA sequence at a targeted point, allowing for a change, as would be required to facilitate CAR T-cell therapy.  Furthermore, the article asserts that “synthesizing an RNA guide is cheaper and more efficient than cultivating retroviral vectors,” potentially allowing for the treatment to be more widespread.  As stated in the Forbes article by William A. Haseltine, former professor at Harvard University, “there is potential to propel CAR T design forward by integrating contemporary innovations such as CRISPR/Cas9 technology.”  It is therefore clear that the usage of CRISPR technology for CAR T-cell therapy could revolutionize cancer treatment

 

 

Many of the concepts referenced in this post involve concepts we have learned in AP bio class.  For example, in the immune system section of the cell communication unit, we learned about the various types of T-cells.  For example, we learned how T-killer cells kill infected cells, such as cancer cells, T-memory cells retain information to prevent further infection, and T-helper cells stimulate other T-cells.  From here, we learned how T-cells, more specifically T-killer cells, can be used to fight cancer, which connects to CAR T-cell therapy’s usage of the cells for gene editing. 

 

While CRISPR technology’s use in CAR T-cell therapy is exciting, according to Haseltine, it “still has room for improvement.”  This technology is not fully developed, and will probably need years to be widespread.  But still, the complete implementation of CRISPR technology in CAR T-cell therapy remains an exciting prospect.

Can We Genetically Modify Humans to Live on Mars?

CRISPR is a gene-editing technique that modifies the genomes of living organisms. They do this by searching for a strand of DNA and “when the target DNA is found, Cas9 – one of the enzymes produced by the CRISPR system – binds to the DNA and cuts it, shutting the targeted gene off.” CRISPR has been used to cure people of genetic diseases. Crispr

Humans have always dreamed of being able to live freely on another planet other than earth. It has been the topic of many pop culture movies throughout history. However with the use of gene editing theoretically this is possible. In a research paper written in 2016, they state that the main problems of living in other worlds would be radiation. With the use of gene-editing they’ve found that the protein named “Dsup prevented the animal’s DNA from breaking under the stress of radiation and desiccation“. It was also able to block X-ray damage by almost 40%. Lisa Nip a scientist at MIT state that “using genetic editing tools like CRISPR to actually transform our own DNA and make ourselves more able to survive in space.” This relates to our AP Bio class as we learned about genes as well as how the genes shape our traits as human. The idea of changing our genes is incredible as we always believed that it’s just how we were born and our parent’s chromosomes determined how we are, but now with CRISPR gene-editing, they can alter our DNA structure. Then through Mitosis, we are able to multiply our DNA, and eventually, all our genes are the edited version.DNA replication cy

CRISPR is rapidly advancing our research of gene-editing as it is the easiest and most reliable way to review gene-editing meaning that people are able to study it easily. This also means that scientist have easy access to it and are able to run many trials on DNA editing. Finally, there is a moral question to ask. Is it ethical to edit a person’s genes even if it helps them? Should we tamper with our human genetics? These questions aren’t very pressing as of now because we are still in the primary stages of gene-editing, however, some day these are going to be upon us. Thank You For reading let me know what you think about gene-editing down below.

Meeting Your Great Great Great… Grandchildren

The MDI Biological Lab along with the Buck Institute of Research on Aging have discovered cell pathways that could increase the human lifespan by 400-500%. “The increase in lifespan would be the equivalent of a human living for 400 or 500 years.” The implications this would have are immense along with some potential drawbacks, but let’s get into the science first.

The research was conducted on C. elegans, a nematode, because “it shares many of its genes with humans and because its short lifespan of only three to four weeks.” The short lifespan allows scientists to quickly see the effects of their efforts to extend the healthy lifespan. The keyword here is “healthy” because prolonging life means nothing unless you can extend the quality as well. The scientists used a double mutant in the insulin signaling and TOR pathways. The alteration in the insulin pathway yields a 100% increase in lifespan and the TOR pathway yields a 30% increase. The incredible discovery though was that when combined the new lifespan was amplified by 500%!! The expected yield was 130%.

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Here depicted is a diagram showing the meaning of a double mutant.

Researchers still say “the discovery in C. elegans of cellular pathways that govern aging, it hasn’t been clear how these pathways interact.” This discovery does lead to the mindset that the important methods of anti-aging are in the interactions between cellular pathways rather than singular pathways. This newly found interaction could also explain why scientists have had trouble discovering “the gene” the governs aging. The combinations of these treatments are described as being similar to the “way that combination therapies are used to treat cancer and HIV.”

It’s odd to picture a world where this treatment could be considered “cosmetic” in a way. Eventually, the human lifespan could expand to hundreds of years with some even living to 1000. The implications that this could have are a current problem we have of overpopulation. It is farfetched, but this would help immensely with the mission to expand into space. The ability to survive with hundreds of years on a potential “colony ship” allows humans to expand to other planets where we would be able to expand greatly. I’ll end with a question: If this treatment was 100% safe and affordable, would you get it? Why or why not?

Genetically Modified Babies?

A decade or two ago, the idea of being able to modify embryos was straight out of a science-fiction movie. However, last November, Chinese scientist He Jiankui genetically modified twin girls’ embryos to have resistance to the HIV virus using a process called CRISPR. His actions have sparked a global panic, as many people feel that current regulations are not enough to keep the scientific community’s actions ethical.

To understand this issue, it is important to understand its individual components. CRISPR is a gene-editing tool that was discovered in 2007 and became widely used in 2013. Essentially, a scientist decides what portion of DNA they would like to alter, and transcribes the sequence into RNA. This RNA finds the portion of DNA with the specific code and then the Cas9 enzyme “cuts” the DNA, allowing a new sequence of DNA to take its place.

The image depicts functions of CRISPR Cas9 technology.

Dr. He used CRISPR Cas9 technology to try to block the HIV pathways in twin girls while they were still embryos. As this experiment was recent, the long-term effects of it are unclear. In addition, as these girls were not developed at the time of their gene editing, they did not give consent to have a treatment that could be detrimental to their health. Furthermore, looking at the Centers for Disease Control website, HIV is primarily acquired by the use of unsafe needles to inject drugs and sexual contact. Using clean needles and condoms can greatly decrease one’s risk of getting HIV, and if a HIV-positive person takes suppression medicines, the viral content of HIV in their blood can become undetectable. Dr. He’s actions gave the twin girls undue risk, with little possible benefit.

In the future, this method of gene editing may be used to prevent or treat genetic diseases, but people have little knowledge of the long-term implications of using this technology on embryos. At the moment, the lack of global legislation regarding this gene-editing technology leaves a lot to be wondered about the future of this tool. According to Victor Dzau who works in the United States National Academy of Medicine, “The silver lining is that the world was awakened by the conduct of Dr. He, and we are all working very, very hard with all good intentions to make sure that this doesn’t happen again—not in the fashion that He did it. And that someday, if and when the technology is ready—and I think all of us are very bullish about this technology—that it will be helping humankind in the right way, knowing the risks and knowing the benefits.” After Dr. He’s experiment, many are in favor of halting the use of CRISPR on human embryos for at least five more years, so more research can be done on the subject. However, legislation, which the world has seen little of, holds a stronger weight than mere recommendations. In Russia, Denis Rebrikov is planning to create CRISPR babies, and regulations in the country regarding his specific goals remain unclear. How will CRISPR embryo editing evolve in the coming decades? Will CRISPR gene editing be as common someday as IVF is today?

 

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