BioQuakes

AP Biology class blog for discussing current research in Biology

Author: sydoplasm

Will Microscopic Worms Replace Dogs in Sniffing Out Cancer?

It is very rare that doctors are able to find cancer at its early stages, however, on the rare occasion that they do there is a much higher chance that the patients survive. You may be asking yourself: Why isn’t there a way to find this cancer earlier inorder to save more lives? A recent study shows that microscopic worms are able to sniff out cancer as early as stage 1. While dogs are also able to smell cancer from human breath, urine, and blood, keeping cancer sniffing dogs in a lab is not practical. These tiny worms create a more practical solution to this problem. 

Specifically, lung cancer is found by doing a biopsy or different kinds of imaging tests. However, these kinds of tests are not able to detect lung cancer until it is in its later stages and more severe. As we learned in AP Biology, cancer is caused by cells that uncontrollably divide. In normally dividing cells there are checkpoints the cell must pass in order to divide. These checkpoints are at the G1, S, and G2 phases. If the cell needs to divide there will be an influx of cyclin concentration and MPF activity. Cyclins are proteins that control the progression of the cell through its checkpoints by activating cyclin-dependent kinases. MPF, or maturation promoting factors, promotes the cell’s entrance into the M phase from the G2 phase. In cancer cells there is a genetic mutation, sometimes it is hereditary, however it can also be caused by caused by tobacco smoking, radiation, etc. This genetic mutation causes these proteins to not work properly. Because of the malfunction of these proteins, cells do not know when to stop dividing and continue to divide. 

A team of scientists from Myongji University in Korea found a type of worm called C. elegans that is attracted to the floral scent of lung cancer cells. 

Caenorhabditis elegans hermaphrodite adult-en

During their experiment, scientists placed the worms in a center chamber. On each side of the chamber was a petri dish, one with lung cancer cells and one with normal cells. The scientist found that these worms were more likely to move towards the lung cancer cells than the regular cells. Now, researchers hope to increase the accuracy of the worm’s attraction to the lung cancer cells and use these worms to detect lung cancer during its early stages. Worms that have already been exposed to the lung cancer cells will be used to detect cancer in patients urine, saliva, and even their breath. These researchers will continue to work with doctors to test their theory and see if these microscopic worms will replace dogs in sniffing out cancer.

 

CRISPR Injections: The Fix for Genetic Mutations?

A recent study shows the first success of CRISPR being directly injected into the bloodstream, reducing the effects of a toxic protein, caused by a genetic mutation, for up to 1 year. CRISPR-Cas9 is a fairly new genetic technology that allows scientists to edit and manipulate specific DNA sequences; it can remove, add, or alter specific sections of DNA. There are two key components that are involved in the CRISPR-Cas9 technology. Cas-9, an enzyme, works to untwist and unzip the DNA at a specific location. This Cas-9 enzyme is very similar to the helicase enzyme. As we learned in AP Biology, helicase untwists and unzips the DNA. However, unlike the Cas-9 enzyme, helicase unzips the whole DNA strand as the DNA is preparing to replicate. The second key component to CRISPR is guide RNA or gRNA. Guide RNA works to guide the Cas-9 enzyme to make sure it cuts the right part of the DNA. 

CRISPR-Cas9 mode of action

A condition called transthyretin (TTR) amyloidosis, inherited from a gene mutation, causes numbness, nerve pain, and heart failure in adults. These symptoms are caused by a buildup of nerves and organs of misfolded TTR proteins, which are made by the liver. Intellia Therapeutics and Regeneron Pharmaceuticals funded research in which scientists figured out a way to fix the genetic mutation. They created a fat particle that contained messenger RNA that codes for Cas-9, CRISPR’s cutting enzyme. This fat particle was then injected into the subjects. Once injected, the gRNA guides the Cas-9 enzyme to cut out the mutated TTR genetic code from the DNA in liver cells. Once this code is cut out, the cells repair the DNA code to a non mutated form; this stops the production of the TTR protein. 

One month after six patients received this injection, these companies reported that the levels of TTR in the patients blood fell drastically. While the symptoms of these patients have not improved, the blood levels gave enough evidence to prove that the injections of CRISPR-Cas9 were successful. In addition, this form of treatment has led to no safety issues. These companies and many others are continuing to test this technology with TTR patients as well as patients with other genetic mutations. 

 

Is the Difference in Size of a German Shepherd and a TeaCup Poodle Due to a Gene Mutation?

Out of all the mammals on the planet, dogs differ in size the most. The biggest dog breeds are around 40 times bigger than the smallest breeds. A recent study has shown that this occurs because of a gene mutation that lies near a gene called IGF1. This gene was originally flagged 15 years ago as playing a major role in the variations of dog sizes. Ancient dogs that were domesticated from wolves in the past 30,000 years differ very little in size, however, in the past 200 years the largest difference in breed size has been recorded as people began to breed the more modern dog breeds during this time. 

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The IGF1 gene was studied comparing to body size of dogs and wild canids. There was one variant that stood out to researchers; this gene mutation was found in a stretch of DNA that works to encode a molecule called a long non-coding RNA. Long non-coding RNAs are a type of mammalian genome that lack protein coding capabilities. Specifically, the long non-coding RNA that was found to affect the size of dog breeds is involved with the levels of the IGF1 protein in the dogs bloodstream. As we learned in AP Biology, mutations in genes occur during the DNA replication phase of mitosis. Mitosis is the division of one mother cell into two daughter cells. DNA replication happens during the S phase of interphase. During this phase, the single stranded chromosome will duplicate and turn into two identical sister chromatids. The mutation will occur when copying the DNA, which would cause the sister chromatids to not be identical. 

This study identified that there are two alleles of this variant. Dogs carrying two copies of the small-bodied allele were most likely to weigh 15 kilograms or less, meanwhile, dogs carrying two copies of the large-bodied allele were most likely to weigh more than 25 kilograms. Dogs that carry one copy of each allele tend to be of an intermediate size. Additionally, dogs containing the larger-bodied allele contain  higher levels of the IGF1 proteins in their bloodstream compared to dogs who carry the smaller-bodied allele. Researchers also recorded a similar relationship in wild canids.

Prior to this study, researchers believed that certain dog breeds were smaller-bodied because of relatively new genetic changes. However, scientists now believe that the smaller-bodied allele is evolutionary and is actually much older than the bigger-bodied allele. They believe this to be true because the smaller-bodied allele was found in coyotes, foxes, jackals, and other smaller canids; this leads us to believe that this allele was present in one common predecessor. More studies must be done to truly determine how these variants impact the levels of  IGF1 proteins in a mammals bloodstream. The IGF1 gene only accounts for about 15% of size variation in dogs, so there is still much more research do be done. This study is just the beginning to really figuring out how we came to have dogs as large as German Shepherds and as small as TeaCup Poodles. Which allele do you think your dog has?

 

Will Shark Antibodies Help Create an End to the COVID-19 Pandemic?

A recent study shows that shark antibodies, known as VNARs, haven proven to be effective in halting the infection of WIV1-CoV in human cells. WIV1-CoV is a type of coronavirus, currently only circulating in bats, where SARS-CoV-2 likely originated from. The study has shown that while this method of COVID-19 prevention is not ready to be put to use yet, it can be used in future SARS outbreaks. 

The anti-SARS-CoV-2 VNARs, unlike human antibodies, are very small and are able to fit in tiny nooks where human antibodies can not fit. The VNARs have the ability to bind to the infectious coronavirus proteins and block their ability to connect with and infect human cells. These shark antibodies were tested against SARS-CoV-2 and a different version of this virus that is unable to replicate in cells, known as a pseudotype. After testing a pool of billions of possible VNARs, three effective candidates were identified. 

Tiburón azul (Prionace glauca), canal Fayal-Pico, islas Azores, Portugal, 2020-07-27, DD 28

The most effective VNAR is called 3B4. The 3B4 VNAR attaches itself to a small groove on the spike protein of the SARS-CoV-2 virus; this process effectively blocked the SARS-CoV-2 spike protein from binding to the human cell. This process is very similar to the actions of a competitive inhibitor. As we learned in AP Biology,  a competitive inhibitor is when a compound, similar to the substrate, competes for the same active site.

These shark VNARs are so important to the research against future and current coronavirus outbreaks because it is effective against all variants of this virus. As stated earlier, these antibodies stop the infection of  WIV1-CoV in human cells; because it halts the infection of the virus where COVID-19 likely originated from, it will be effective to all COVID-19 variants. Additionally, with more research these different antibodies can be used together if proven to be more effective. The shark antibodies are cheaper and easier to manufacture compared to human antibodies. While this method of protection against COVID-19 has yet to be tested on humans, with more research this could be the new way that humans protect themselves against all SARS-CoV viruses to come. What do you think?

 

 

How Does the New COVID-19 Pill Work? Has it Proven to be Effective?

The COVID-19 pandemic has affected so many lives across the world. Many people wonder when society can return back to “normal life”. While vaccines are a great and effective way to begin the process of protecting people against SARS-CoV-2, a professional must administer the shot which may be time consuming and immunizations require more resources than other medications such as pills. Recently there has been more positive research on a new pill that helps the body fight SARS-CoV-2. This pill is a game changer to the future of the COVID-19 pandemic as it can be taken at home rather than vaccinations which must be administered by a healthcare professional.

Pill 1

A new study shows that an at-home pill cuts the chance of hospitalization  of newly diagnosed SARS-CoV-2 patients in half. This pill is comprised of an antiviral drug called molnupiravir; molnupiravir is the first oral medication proven to be successful in reducing the viral COVID-19 RNA. The pill was tested in a pool of subjects who were at high risk of developing severe illness once diagnosed with COVID-19. Of the subjects, 377 patients received the placebo and 385 patients received the molnupiravir pill. Within 29 days of beginning the trial, 14.1% of patients who received the placebo were hospitalized, eight of which died. Within this same time frame, 7.3% of patients who received the pill were hospitalized, none of which died. It is important to note that not only did the pill decrease hospitalizations by about half, but this medication also worked for gamma, delta, and mu variants of SARS-CoV-2. 

Once the SARS-CoV-2 virus has entered the body’s cells, it replicates its RNA. The complete virus particles exit the cell and begin infecting other cells which begins the virus’s rapid spread throughout the body. As we learned in AP Biology, helper T cells secrete cytokines which activate the adaptive immune response . However, when SARS-CoV-2 without backgroundtoo many cells are infected there are a lot more helper T cells secreting cytokines into the bloodstream; this is referred to as a cytokine storm. A cytokine storm can result in dead tissue or damage to organs and is an unfortunate COVID-19 complication. However, this pill works to disrupt the SARS-CoV-2 RNA reproduction. Once the molnupiravir drug is absorbed into the virus infected cells, it is converted into defected nucleotides(building blocks of RNA). When the virus attempts to replicate, it is unable to because its genetic code is defective. Because it can not replicate, the amount of virus in the body will remain low. Due to the low SARS-CoV-2 viral count, the virus is less harmful which is made evident in the study summarized above. 

It is evident that this pill is effective and can save many lives. Do you think this could be a turning point in the COVID-19 pandemic, leading the beginning of life as we knew it before March 2020?

 

Are Genes Inherited from Neanderthals Protecting People Against COVID-19?

Neanderthals, from roughly 40,000 years ago, have had an impact on protecting people, that contain a specific haplotype on chromosome 12, from having severe symptoms due to the Sars-COV-2 virus. Researchers conducted a study that showed a ~22% decrease in severe illness connected to a gene inherited from Neanderthals.   

Neanderthals evolved in western Eurasia -the largest continental area consisting of Europe and Asia- about half a million years ago, living mostly separated from early modern humans in Africa. Neanderthals likely developed certain genes allowing them to fight off infectious diseases during the time of their existence. Due to natural selection, which is when animals with the most favorable traits for survival will survive to reproduce and pass on their genes, these neanderthals were able to evolve and pass on the favorable gene allowing modern humans today to fight off Sars-Cov-2. Through natural selection, the haplotype, on chromosome 12, linked to protection against certain viruses has been passed on. This specific haplotype has helped people during the current pandemic to stay out of the hoHuman male karyotpe high resolution - Chromosome 12spital. 

This study discovered that this specific haplotype on chromosome 12 contains three helpful genes: OAS1, OAS2, and OAS3. These genes encode for a specific enzyme called oligoadenylate synthetase. As we learned in AP Biology, enzymes are created by free ribosomes in the cytosol; the ribosomes manufacture proteins(a chain of amino acids), such as enzymes for cellular reactions. The oligoadenylate chain triggers ribonuclease L. The ribonuclease L, also known as RNase L, is only activated when a viral infection enters the body; it breaks down the viral RNA molecules, leading to autophagy. This enzyme breaks down the viral Sars-Cov-2 RNA and slows/stops the spread of the virus in the body. 

Many people have been trying to find ways to move forward from this pandemic and return to our previous form of normal life. Scientists may be able to use this information about this specific haplotype on chromosome 12 with gene editing technologies, such as CRISPR, to help individuals slow and later stop the spread of COVID-19. Research like this may be one way to be able to return to a normal life-style and keep people out of hospitals from COVID-19. As we continue on in AP Biology this year, I look forward to learning about the idea of genes and gene editing as I will have more knowledge to touch back on this research study. Do you think that this is a possible solution to the COVID-19 pandemic?

 

 

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