BioQuakes

AP Biology class blog for discussing current research in Biology

Author: anaplasia

CRISPR Tomatoes Help You De-Stress

Tomato jeFor the first time, genome-edited food is being sold on the open market. A recent article published on December 14th, 2021 outlines how CRISPR-Cas9 technology has been used to create genome-edited food. Consumers in Japan have been able to purchase genetically edited Sicilian Rouge tomatoes through the Tokyo-based company, Sanatech Seed. These genetically edited tomatoes have been altered to have high amounts of y-aminobutyric, aka GABA. 

In Japan, consuming GABA is very popular. It is supposed to lower blood pressure and promote relaxation. It does so through reducing the excitement of neurons in the nervous system. GABA is an inhibition neurotransmitter in the nervous system.

To test its audience, in May 2021 Sanatech first sent seedlings for genome-edited tomatoes to 4,200 home gardeners in Japan. Because of the positive feedback and high demand, Sanatech started selling tomatoes to the general public.

The tomatoes are altered through CRISPR-Cas9 genome editing. CRISPR has successfully been used to alter foods, such as making mushrooms that don’t brown, or soybeans that are tolerant to drought. Although many foods have been regulated, these tomatoes by Sanatech are the first to be commercialized.

CRISPR Cas9 technologyCRISPR is a technology that can be used to edit the genes of prokaryotic organisms like archea and bacteria. CRISPR is a way of finding a specific sequence of DNA in a cell, and then altering that DNA. CRISPR-Cas9 (pictured to the right) is the enzyme which finds and binds with specific DNA strands complementary to the CRISPR sequence.

DNA simple2DNA is a polymer which carries the genetic instructions for an organism. It is made up of two strands of bases (two polynucleotide chains) which compliment each other. Each base in a strand of bases can be one of four nucleotides, adenine, thymine, guanine, and cytosine. One nucleotide, or base, on one side of the DNA double helix matches with the corresponding base on the other side of the DNA to form a base pair. Adenine nucleotides must match with thymine, and guanine must match with cytosine.

GRNA-Cas9Sanatech increased GABA in the tomatoes by altering GABA’s metabolic pathway, aka the GABA shunt. They first inserted a strand of guide RNA along with the enzyme CRISPR-Cas9. This guide RNA is a strand that compliments the part of the DNA strand Sanatech wishes to disable: the gene that encodes CaMBD (calmodulin binding dominant). The RNA strand attaches, and the enzyme CRISPR-Cas9 cuts the DNA sequence Sanatech wishes to remove out. Disabling the gene that encodes CaMBD increases the enzyme glutamic acid decarboxylase’s activity. This enzyme catalyzes the decarboxylation of glutamate to GABA, raising GABA levels.

Increasing GABA levels is said to be a healthy way to decrease stress and lower blood pressure, and people around the world love being able to do so through eating everyday foods, such as tomatoes. People are also more accepting of these genome altered tomatoes because they have been edited specifically by CRISPR, which is a pretty trusted and well known form of gene editing technology. CRISPR technology has, and will, change the world by giving humans the power to alter and change DNA.

The Promise of Messenger RNA Therapy

A recent article about messenger RNA therapy outlines the evolution of messenger RNA therapy and how it has gone from an idea to a globally used treatment in just the past seventeen years. Recently, messenger RNA therapies such as the Pfizer-BioNTech and Moderna COVID-19 vaccines have been used by hundreds of millions of people around the world. 

The author Drew Weissman, a vaccine research professor at the University of Pennsylvania, and his colleague Katalin Karikó created mRNA molecules back in 2005 that would not cause harm when injected into animal tissue. Then in 2017, Weissman and Norbert Pardi found that this mRNA creation could be brought into human cells through a fatlike nanoparticle without harm, and that bringing this modified mRNA in protect mRNA from being broken down by the body and resulted in the immune system generating antibodies and more effectively neutralize the invading virus. Vaccines-09-00065-g001This mRNA fatlike nanoparticle is known as mRNA-LNP (pictured to the left). mRNA is able to enter cells without harm because it is carried in by this liquid nanoparticle which is known for its role in transportation. The Pfizer-BioNTech and Moderna COVID-19 vaccines use this mRNA-LNP, and in clinical trials have shown to successfully prevent over 90% of treated people from contracting COVID-19.

The positive results from many trials and studies of the Pfizer-BioNTech and Moderna COVID-19 vaccines have provided a lot of information on the success of mRNA-LNP. It has been found that mRNA-LNP is much more effective and quicker than other approaches to COVID-19 treatments such as growing vaccines in laboratory cell cultures. 

41541 2020 159 Fig1 HTMLMessenger RNA therapy works by making cells create proteins that induce a reaction from the immune system in response to invading viruses (pictured to the right). This reaction in response to invading viruses is called the humoral response, where cytotoxic T cells are made to release proteins that destroy infected cells. The humoral response also trains the immune system to respond to and attack that virus in the future by creating memory B cells to recognize it, which is called a secondary immune response.  This method of instructing cells to create these proteins yields a greater quantity at a time that conventional protein and monoclonal antibody therapies. 

The success of messenger RNA therapy in COVID-19 vaccines has inspired the further research and use of this method for other viruses, as well as cancers, food, allergies, and autoimmune diseases, and many clinical trials are underway. Messenger RNA therapy could be a much more time and cost efficient alternative for a lot of conditions and treatments. More research still needs to be done, and there are many improvements that could be made (such as smaller doses of or a better supply chain for the vaccine), but overall messenger RNA therapy is very promising for treatments of the future.

The Discovery of Time Cells and Their Time Stamps

Have you ever wondered how we remember things, how we know one event followed another, how we are able to chronologically compartmentalize our memories? A recent article on a study published this summer in the Journal of Neuroscience reveals that time cells found in the hippocampus may be the answer. 

Neuroscientist Leila Reddy of the French National Center for Scientific Research and her team conducted a study to confirm the existence, and reveal the function of time cells in the brain through understanding how neurons in the hippocampus relay temporal information. 

HippocampusThey found that these time cells consecutively fire during tasks in order to organize the specific moments of an experience in accordance to time. The study also confirmed that these time cells exist in the hippocampus (pictured on the right), which is an important location for memory processing. As an event plays out and a memory is created, these time cells turn on and start firing, recording each moment with a chronological time stamp. The work done in this study is crucial as it reveals a key component in memory formation and function.

The co-author of the study, Matthew Self of the Netherlands Institute for Neuroscience, further relayed the importance of their findings, saying they believe “that time cells may be the underlying basis for encoding when something happened.” 

Time cells have been known to exist in rodents for a while now, but this study, conducted just late last year, was the first to identify these time cells in the human brain as well. But the study did not stop there. Reddy and her team continued to investigate these time cells. They looked at the hippocampal activity of willing epilepsy patients with electrodes implanted in their brain.

A schematic of the neuroprosthesis showing the external control unitPatients with epilepsy were most likely chosen for this study because their nerve cells communicate with one another in abnormal ways and send each other messages that get mixed up. Electrode implants would not only benefit the patient by producing impulses to regulate abnormal impulses, helping with an preventing seizures, but would work well for the study because the implant also allows neuron activity to be monitored (shown to the left).

About one week after their electrode implant surgery, the patients would participate in two experiments, during which their hippocampus activity would be monitored. The first experiment presented the patients with a sequence of five to seven images containing different settings or people – each image shown for 1.5 seconds with a .5 second break in between. This sequence was presented to the patient several times in the same order. Randomly, for one fourth of the intervals, the sequence would pause and the patient would be asked to identify which of two images should be the next one to occur. The research in this study found that, for all sixty repetitions of the sequence, all of the time sensitive neurons in the hippocampus of the patients fired at specific moments between each random pause in the sequence.

The second experiment was the same, except it included another component: a distraction. A black screen would show for 10 seconds after five sequences were repeated to half the patients, and after two sequences were repeated for the other half. The sequence was repeated to both groups a total of 30 times. In this experiment the patients were again tested about the order of the images. The results showed that neurons would fire corresponding to specific images, and that the time cells still turned on during the 10 second black screen distraction. The black screen was found to actually kelp the patients remember the correct order of images.

To find if there was time information in the activity of neurons in the hippocampus, the researchers stimulated time cell neurons already activated by an image in the experiment to test the firing activity of each neuron as a specific moment in time connected to a specific image. As a result they found that, “the activity pattern across the hippocampus [appeared] to simultaneously provide [them] with both the time stamp and the contents of the experience,” said Matthew Self. The researchers ability to decode moments in time from the neuron activity proved that the hippocampus in the human brain contains neurons capable of time-tracking.

These findings could explain why damage to the hippocampus can result in individuals having the ability to recall events, but not place them in chronological order. This problem is also seen in Alzheimer’s patients and those with other neurodegenerative conditions. A better understanding of cellular contributions to memory function can help us understand how and why people suffer from memory loss diseases, and give us a little bit of hope for the possibility of finding new and improved treatments and preventions.

 

SARS-CoV-2 and Our Evolving Immune Systems

A scientific study analyzed in a recent article by Monique Brouillette brings hope with the emergence of possibly more infectious COVID-19 variants. The study looks at the blood of people who are vaccinated, and people who recently have had COVID-19, to learn more about the cells in our immune system. Studying and seeing these cells create their own way to counteract mutations could mean the evolution of our immune systems in response to the variants. So the study poses the question: Along with our cells ability to respond to the initial SARS-CoV-2 virus invasion, do our bodies adapt so that those same cells can recognize the new variants?

An Immunologist at the Rockefeller University, Michel Nussenzweig, conducted a study along with his colleagues by testing the blood of individuals both one month and seven months after they had COVID-19. The scientists noticed that individuals had lower levels of antibodies, and equal or higher levels of memory B cells, seven months after having COVID-19 than one month after. This was expected as the virus had been fully cleared by the seven month mark, and memory B cells were created in response to the initial invasion of SARS-CoV-2.

Memory B cells are created by the humoral response. This is when macrophages or dendritic cells recognize a forign antigen (in this case SARS-CoV-2), and stay in the body near its lymph nodes with the ability to recognize the virus.

Memory B cell response

If someone were to get infected for a second time, these memory B cells would activate to quickly produce antibodies and block the virus. This is called the secondary immune response (pictured on the right).

The scientists then did another test in the study. They tested reserve B cells and antibodies someone produced in response to SARS-CoV-2 against a version of SARS-CoV-2 they created to be more like a new variant. The replica new variant virus was made to be more like the new variants by having a mutation in the spike protein, which is the part of the virus that binds to our cells. When they tested this, they saw that some reserve B cells produced antibodies that went and attached to the mutated spike proteins, showing that the reserve B cells and antibodies from SARS-CoV-2 were able to adapt and recognize a different or mutated version of SARS-CoV-2.

New COVID19 mutant (SARS-CoV-2 VOC-20201-01)

Example of SARS-CoV-2 Mutation

The SARS-CoV-2 variants have many similar elements to the original SARS-CoV-2, but also contain mutations in their spike proteins and receptor binding domains (for the most part), which allow them to usually go undetected by our bodies. This is why those who are vaccinated or have SARS-CoV-2 antibodies are not fully immune to the variants.  

Most recently, Nussenzweig and his team conducted the same experiment again, but with new and improved viruses that more closely resemble the COVID-19 variants. One of the replica variants is of B.1.351, which contains mutations K417N, E484K, and N501Y, was tested against cloned six month old (previously exposed to SARS-CoV-2) B cells. Although it has not yet been reviewed and confirmed, this test did show that some of the antibodies produced by these B cells had the ability to recognize and attach to these mutated variants engineered to be very similar to the viruses of the Covid variants. 

What these scientists discovered with SARS-CoV-2 is a process called somatic hypermutation. This is when the immune system adapts to recognize and attack forign mutations or viruses it has not seen before when they have previously fought off a virus with some similar elements. The occurrence of this process with SARS-CoV-2 gives us hope that after getting the vaccine or having had COVID-19, our bodies will have a better defense against the new variants, which will, hopefully, in turn, lessen the fear and stress surrounding the emergence of new SARS-CoV-2 variants.  

 

 

 

Smoking Can Harm More Than Just Your Lungs

When you think of the damage smoking does to your body, you think of your lungs, right? Well, did you know that smoking can actually harm your eyes?

Tobacco has previously been proven to be linked to many leading causes of blindness and vision impairments such as cataracts, glaucoma, and macular degeneration, but all of these effects occur in the inner part of the eye. A new study shows that smoking can actually harm and kill cells on the surface of your eyes.

Research from a recent study conducted by Wataru Otus, a biomedical researcher at the Gifu Pharmaceutical University in Japan, and his colleagues, published by Scientific Reports, found that the compounds found in the smoke of cigarettes and smoking devices cause an iron buildup in the corneal epithelium (the outer layer of corneal tissue on the eye), which can harm and kill cells.

In the study, the researchers exposed human epithelium cells to smoke extract of a cigarette as well as that of heated tobacco devices, and recorded their observations. The researchers found that after 24 hours, more cells that were exposed to cigarette and heated tobacco smoke were killed than those not exposed. They also found that smoking tobacco or using heated tobacco devices caused damage to the cells of the outer eye regardless of nicotine or tar being involved.

The cells that were exposed to tobacco products had damaged cell membranes, lumps of iron, and a lot of damaged ferritin, which strongly indicated ferroptosis, a form of programmed cell death.

Ferroptosis human prostate cancer modelFerroptosis occurred when the compounds in the tobacco made contact with the cells on the outer layer of the eye. The compounds caused the ferritin proteins inside the cells – which store and release iron – to break down and release the iron they were storing. Some of the iron that was released bunched up and produced hydroxyl radicals. Hydroxyl radicals are known to be a very reactive species that attacks organic molecules by removing or deteriorating them. In this case, the hydroxyl radicals attacked the lipids in the film on the surface of that eye, an event called lipid peroxidation. When these lipids are attacked and/or destroyed, your eye is much more likely to dry out, because lipids help prevent the eye from drying out due to their role as lubricators. This is why smokers tend to suffer from dry eye syndromeWhen too many radicals accumulate and are damaging the lipids in the cell membranes, cells can die. The death of eye cells (aka photoreceptors) can lead to the loss of or impaired vision.

As a solution in the study, the researchers found that by adding chemicals that are known to block ferroptosis to the human epithelium cells, more cells exposed to tobacco were able to live, suggesting that ferroptosis treatment could help smokers suffering from eye problems.

Moreover, ophthalmologist Dilek Altinörs of the Başkent University in Turkey, who has studied the results of this study, also suggested that smokers experiencing eye problems should use tear drops with ferroptosis blocking compounds. Although, further study needs to be done on the effects and successfulness of this treatment method. 

The findings of the study help one understand how and why it is that cigarette and tobacco devices affect the eyes of smokers, and show treatments for ferroptosis as a possible treatment for smokers’ having eye troubles. But the obviously best way to prevent smoking from harming your eyes is to not smoke at all. Having smokers learn and understand this new information will hopefully show them yet another reason why smoking is harmful, and why it is in their best interest to quit. 

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