BioQuakes

AP Biology class blog for discussing current research in Biology

Author: lucytoplasm

Paving The Way For Discovery: Gene Editing In Ticks

What is something that reminds you of summer and your childhood? For me, it is ticks. I know it sounds strange, but the constant reminders from my parents to “check for ticks” after long summer walks are ingrained in my memory. Although the practice of checking for ticks is common, we don’t often stop to question why, or take a moment to expand our knowledge as to just how dangerous a summer walk in long grass could be. Ticks, although tiny, are powerful, disease ridden organisms and have the potential to spread diseases to humans such as Lyme’s disease, Babesiosis, Anaplasmosis, Tularemia, etc. 

tick

Despite their ability to pass on such a vast variety of pathogens, research on ticks is extremely limited, especially in comparison to similar organisms like mosquitoes. The challenge when it comes to gene editing in ticks is that tick embryos are very difficult to inject due to high pressure in the eggs, a hard outer shell on the egg, and a wax layer outside the embryo created by Gene’s organ. In a recent study published in iScience, researchers developed a tick-embryo injection protocol that aimed to target gene disruption with CRISPR-Cas9 (using both embryo injection and Receptor-Mediated Ovary Transduction of Cargo. In this technique, researchers removed Gene’s organ to prevent the wax coating along with treating the eggs with chemicals such as benzalkonium chloride and sodium chloride to remove the outer shell and relieve the inner pressure. Gulia-Nuss, the co-author of the study and a molecular biologist at the University of Nevada, states: “Another major challenge was understanding the timing of tick embryo development. So little is known about tick embryology that we needed to determine the precise time when to introduce CRISPR-Cas9 to ensure the greatest chance of inducing genetic changes.”

Essentially, the CRISPR-Cas9 system consists of two main molecules that introduce a mutation to the DNA. The first is an enzyme known as Cas9. The function of this enzyme is to cut the strands of DNA at a specific location in order for pieces to be added or removed. As we learned in AP Bio, enzymes are key when it comes to DNA and DNA replication, for they play a variety of roles that allow DNA to replicate the way it does. For example, helicase untwists the double helix at the replication fork, topoisomerase relieves the strain of twisted DNA strands by breaking and rejoining them, and primase synthesizes short RNA strands that act as a primer. Without these enzymes and their very specific purposes, DNA would not be able to replicate. In the case of Cas9, it performs the essential job of cutting DNA in order for gene editing to occur. The second piece of the system is a piece of RNA called guide RNA. The guide RNA binds to a specific sequence in the DNA due to its RNA bases that are complementary to those of the DNA sequence. 

Prior to this study, no lab had displayed the possibility for gene editing in ticks, due to the daunting technical difficulties of such a task. This study is proof to embrace the difficulty and the challenges, in life and in science, for often the most difficult of tasks lead to the greatest outcome. In the case of this study, the discovery of ways in which to target the disruption of genes in ticks will pave the way to the uncovering of the molecular biology of tick-pathogen-host interactions, hopefully in the long run creating ways to prevent and control tick-borne diseases, a process that has the potential to save lives.

Could These Blood Proteins Be The Key To Extending Human Lifespan?

All around the world, companies profit off of the idea of “anti-aging” products; but could these various serums, skincare products, and supplements even have an impact? A study from the University of Edinburgh, in which researchers analyzed six different genetic studies surrounding human aging, suggests otherwise. Instead, after analyzing 857 proteins from genetic information from hundreds of thousands of people, scientists have reason to believe that two distinct blood proteins have negative effects on aging. As we know from AP Bio, different individuals naturally have higher or lower levels of certain proteins depending on their genetics, and the DNA they inherit from their parents. Additionally, we know that each parent provides 23 chromosomes, which encode the same genes, totaling to 46. This means that if your parent has high levels of specific proteins, you have a significant chance of inheriting that.

Ácido desoxirribonucleico (DNA)

 In the case of these two blood proteins, LPA and VCAM1, people who inherited DNA that causes raised levels of these proteins were overall much more weak, unhealthy, and less likely to live a long life. Lipoprotein (a), a lipoprotein variant containing a protein called Apolipoprotein (a), is made in the liver. High levels of this protein are associated with a vast increase in the risk of atherosclerosis, which is a cardiovascular disease in which there is a​​ thickening or hardening of the arteries caused by a buildup of fatty substances in the inner lining of the arteries. Additionally, LPA is also linked to coronary heart disease and strokes. The second protein, vascular cell adhesion protein 1, or VCAM1,  is a protein found mainly on endothelial cells lining the blood vessels. It primarily controls blood vessel expansion and retraction. Elevated levels of VCAM1 are associated with long-term risk of heart failure.

Currently, there are clinical trials working to reduce the risk of heart disease through testing a drug to lower LPA. While there are no trials surrounding VCAM1 at the moment, there has been some animal testing done on mice to see the effects of lowering this protein. In these tests, researchers found that antibodies lowering VCAM1 levels improved cognition in old age for the mice.

The scientific progress and research regarding these two blood proteins is profoundly important, for it has revealed two key targets for future drugs to extend the lifespan of humans who aren’t genetically blessed. It is medical progress and news like this that continuously help us remain hopeful as we, and our loved ones, age.

Not 1, But 2: The Antiviral Pills That Could Change The Game For Covid-19

Right on time. As cases begin to rise again due to the omicron variant of SARS-CoV-2, the race for treatments against the virus becomes more urgent. Well, celebration is in order, for both Merck and Ridgeback Biotherapeutics and Pfizer have developed antiviral drugs in the form of a pill to fight the virus. 

Molnupiravir, the drug created by Merck and Ridgeback Biotherapeutics, and Paxlovid, Pfizer’s antiviral pill, are both pills that can be taken at home when one identifies early signs of Covid in themselves. For Merck, the latest data reads that their pill cut the rate of hospitalization or death by 30%. On the other hand, Paxlovid’s trial displayed reduced death and hospitalization rates of 89%, as long as the pill was consumed within 3 days of symptoms. 

Both effective medications and exciting progress, these two contrasting antiviral pills work in two distinct ways to stop viral replication. As we learned in AP Bio, viral replication is what occurs when a virus escapes the innate immunity responses, or the 1st line of defense, and enters the nasal epithelium, replicating in nasal passages and tissue fluids. This is what makes immunity responses to viruses often a long process, and is why we have to take sick days to allow time for our B and T cells to destroy the many invading pathogens and infected cells, respectively. A nucleoside analogue, Molnupiravir disguises as one of the aspects of RNA that makes up SARS-CoV-2. Normally, once inside the cells the virus would use a polymerase enzyme to assemble all the pieces of RNA into new copies of viral RNA, ultimately replicating itself. However, with the Molnupiravir drug’s deception, the virus creates new versions of itself with defective genetic materials, making it noninfectious. In juxtaposition, Paxlovid has a similar process of HIV treatments in that it is a protease inhibitor. After replicating its RNA, SARS-CoV-2 makes a large polyprotein containing all of the virus’s parts. But to function properly, this polyprotein must be broken into many small pieces by the enzyme protease. What Paxlovid does is it blocks that enzyme from its function, preventing the necessary production of small virus particles. Again like protease inhibitors for HIV, though, the Pfizer drug requires a second drug called ritonavir to make it last longer (like a booster).

COVID-19 Virus

Because both of these antiviral pills target the immune response in a general, nonspecific way (the replication process), they can work similarly against many different coronaviruses found in animals such as ​​bats, pigs, people, and mice. This is not only reason to believe these pills will probably be effective against other variants such as omicron, but it also means this scientific progress plays a role in fighting future pandemics, as well as the current one. 

While it is easy to get caught in the incessant loop of bad news concerning the pandemic, especially lately, I recommend balancing that awareness of threats with the acknowledgement of the improvements and steps forward, for everyday scientists are hard at work fighting this pandemic. In a similar lens, our work in AP Bio with beginning to understand immunology and how viruses work is our baseline in becoming the future of medicine, doctors, and scientists!

Fermented and Fabulous: The Key to Gut Health

Fermented foods are truly underestimated. Yes, I’m talking kombucha, kefir, yogurt, sauerkraut, kimchi, etc. You might be thinking, how much can consuming a bitter tasting food really do for me? The truth is, a lot. Fermented foods may just be the answer to combating the rise in chronic inflammatory diseases. This is due to the fact that a diet with an abundance of fermented foods enhances gut microbe diversity. Gut microbiota, the human body’s largest population of microorganisms set in the intestine, are essential to the multifaceted nature of human health because they have impacts on immune, metabolic, and neurobehavioral traits.

Improving Human Intestinal Health

 In a trial run by Stanford School of Medicine, 36 healthy adults were assigned to a 10 week diet of either fermented or high-fiber foods to test the effects on gut microbiome and the immune system as a whole. The study discovered that those who consumed a diet rich in fermented foods had an increase in microbial diversity, four types of immune cells showed less activation, and the levels of 19 inflammatory proteins measured in blood samples decreased. Proteins, as we learned in AP Bio, have many different functions and structures and just one changed amino acid in the structure can cause diseases or viruses because its characteristics (hydrophobic vs. hydrophilic, non-polar vs. polar) are altered. One of these inflammatory proteins decreased by fermented food consumption, interleukin 6, has been linked to conditions such as rheumatoid arthritis, Type 2 diabetes and chronic stress. The success and promise that these results provided were immeasurable, for gut microbes have the potential to defend against harmful microorganisms, digest certain foods, produce important molecules like short-chain fatty acids, facilitate the absorption of dietary minerals, synthesize essential vitamins and amino acids, and even shape mood/behavior. Along with that, research suggests that low microbiome diversity has been linked to obesity, diabetes, arthritis, eczema, and even types of cancer, so any chance to increase microbial diversity is an opportunity to leap to. 

On the contrary, in the study, those adults assigned to a high-fiber diet saw no inflammatory protein decrease and the diversity of their gut microbes remained on average the same. Through a final step of analyzing blood and stool samples collected throughout the trial, the scientists confirmed that short term dietary changes involving a diet rich in fermented foods/drinks can rapidly increase microbial diversity, resulting in a series of health benefits that ultimately aid in protection against serious health issues and in general just keep you healthy and happy! 

So next time you’re at the grocery store, pick up that bottle of kombucha. It may look questionable, but tastes pretty good and has so many health benefits!

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