BioQuakes

AP Biology class blog for discussing current research in Biology

Author: sydeousmembrane

How Does Activation of p53 Effect the Use of CRISPR?

In a study conducted at Karolinska Institutet in Sweden, researchers looked into CRISPR gene editing and how that can play a critical role in mutated cancer cells as well as the medical field. CRISPR is “programmed to target specific stretches of genetic coding and to edit DNA at the precise location;” specifically, the CRISPR system binds to the DNA and cuts it, therefore, shutting the targeted gene off. Researchers can also permanently alter genes in living cells and organisms, and in the future, using this method they may even be used to treat genetic causes of diseases. Although CRISPR sounds amazing, will it really be as great as it seems?

CRISPR CAS9 technology

CRISPR

There are a few obstacles that need to be overcome before CRISPR can even become regularly administered in hospitals. The first is to understand how cells will behave once they are subjected to DNA damage which is caused by CRISPR in a controlled manner. When cells are damaged they activate a protein called p53 which has negative and positive effects on the procedure. The technique is less effective when p53 is activated, however, when p53 is not activated cells can grow uncontrollably and become cancerous. Cells, where p53 is not activated, have a higher survival rate when subjected to CRISPR and because of this can accumulate in mixed cell populations. Researchers have also found a network of linked genes that have a similar effect to p53 mutations, so inhibiting p53 also prevents these cells from mutating. 

Long Jiang, a doctoral student at the Department of Medicine at Karolinska Institutet, says that “it can be contrary to inhibit p53 in a CRISPR context. However, some literature supports the idea that p53 inhibition can make CRISPR more effective.” By doing this it can also counteract the replication of cells with mutations in p53 as well as genes that are associated with the mutations. This research established a network of possible genes that should be carefully controlled for mutations during CRISPR. This will hopefully allow for mutations to be regulated and contained more efficiently.

DNA, or deoxyribonucleic acid, is a long molecule that contains a genetic code; “like a recipe book it holds all the instructions for making the proteins in our bodies.” Most DNA is found in the nucleus of the cell, but a small amount can also be found in the mitochondria. DNA is a key part of reproduction because genetic heredity comes from the passing down of DNA from parents to offspring. Altering this DNA can have an impact on a number of someone’s physical characteristics. CRISPR does just that. It can be used to edit genes by finding a specific piece of DNA inside a cell and then modifying it. Since CRISPR is so new, it has its positives and negatives, but overall it is a groundbreaking discovery. 

DNA double helix horizontal

DNA

In conclusion, even though cells seem to gain p53 mutations from CRISPR, it has been discovered that most of the cell mutations were there from the start. Even though this is still an issue, we don’t know to what extent it can cause greater harm, so it will be exciting to see the new discoveries in the future!

What is the Real Reason Dog Breeds Vary in Size?

Dog (Canis lupus familiaris) (6)

Do you like big dogs or small dogs? This question is frequently asked, but how did we even come about having this option? Ancient domesticated dogs in the past 30,000 years differed in size but nothing as extreme as the modern size differences. Dogs now can range from 40 times in size, and these drastic differences emerged just in the past 200 years as humans started establishing more and more breeds. In a study conducted by Ewen Callaway, he looked at why dogs differ so much in size and how a mutation could be the cause of this. The mutation behind all of this has been traced all the way back to ancient wolves. It lies near a gene called IGF1(insulin growth factor) which researchers found to have a major role in the size variations of domestic dogs. IGF1 is a hormone that manages the effects of growth hormones and is primarily produced by the liver so liver diseases can cause its levels to change.

One variant stood out when comparing the region around IGF1 and dog sizes. This variant “lies in the stretch of DNA that encodes a molecule called a long non-coding RNA which lives in controlling levels of the IGF1 protein.” A gene variant is a permanent change in the DNA sequence that makes up a gene. Variants can be inherited from a parent or can just occur during a person’s lifetime. If a variant is inherited from a parent they are present in pretty much every cell of the body while a variant that occurs during someone’s lifetime is present only in certain cells. Most variants that lead to disease are not common in the general population; however, some variants occur often enough in the general population to be considered common genetic variations. Examples of this would be eye color, hair color, and blood type. Even though DNA variants can be seen as a negative, as it is explained not all variants produce fatalistic effects.

There are two identified versions (alleles) of the variant, which Callaway identified. An allele is a form of a gene and each organism inherits two alleles, one from each parent. Dogs who have two copies of one allele typically weigh more than 55 pounds and have higher IGF1 protein levels in their blood. Whereas, dogs with two copies of the other allele tend to weigh less than 33 pounds. In addition, there are dogs with one copy of each version and they tend to be intermediate in size. Researchers determined that the same relationship was present in other canids as well, such as foxes, coyotes, and wolves.

Protein IGF1R PDB 1igr

IGF1 structure

The allele linked to small-bodied animals is seen to be much more evolutionary than alleles linked to large-bodied animals. Coyotes, jackals, foxes, and a lot of other candids have two copies of the small version, suggesting that this variation could have been present in their ancestors. However, it is not as clear as to when the large-bodied allele formed. It has been traced back 53,000 years ago to an ancient wolf living in Siberia, and since then has been found in other ancient wolves. Robert Wayne, an evolutionary biologist at UCLA, states that the view used to be that animals that have a small body size can be linked to genetic changes that could be unique to domestic dogs. This study could be a sign that dogs were domesticated from smaller wolves rather than present-day gray wolves.

Overall researchers have discovered a big part as to why dogs vary so much in size, however, the story of dog size is far from complete as IGF1 proteins only make up 15% of the difference in dog size. Even though this is such a small percentage, we are 85% closer to finding the whole meaning.

New Covid-19 Pill! Will it work?

Pill 2

In a study conducted by Tina Saey, she looked at Merck’s Covid- 19 pill Molnupiravir and how it is affecting hospitalization rates of Covid-19. Molnupiravir, “an antiviral drug that can be taken at home” is the first medicine that can be taken orally that is approved to help fight off Covid-19. The drug is typically administered to patients who have mild to moderate Covid within five days of their symptoms appearing. Molnupiravir has been tested several times and is now waiting on the FDA for formal approval. This new pill could be a game-changer, but will it really be as great as it seems?

Ms. Saey states that “finding an early treatment hasn’t been easy”, so when Molnupiravir came around experts praised its development. Initially, the pill showed great signs of preventing hospitalizations and death from Covid-19. The results were so promising, a 48% decrease in hospitalizations, that the trial ended early so that the pill might become available to the public faster. However, when all the data was collected and analyzed the reduction in hospitalization rate dropped to 30%. The unexplained decrease happened when participants in the placebo group were no longer experiencing severe symptoms. Due to the decrease in reported effectiveness, the FDA’s antimicrobial drugs advisory committee came to a split 13-10 decision on whether the drug should be available for emergency use. 

The main concern for authorizing Molnupiravir is that the pill could create even more dangerous versions of the Covid- 19 coronavirus. The drug works by making mutations in the RNA. This is when a change occurs that affects nucleic acids, the building blocks of RNA. A handful of these mutations could land in the spike protein. Spike proteins interact with the cell receptors located on the host cell; in terms of Covid-19 it helps the coronavirus break into cells. The spike protein could also burst into other proteins making the virus more transmittable. James Hildreth, an immunologist stated that, “the potential for this drug to drive some very challenging variants into the public is of major, major concern.” Although this is a possibility it seems unlikely because, after five days of usage, infectious viruses in participants taking Molnupiravir were no longer detectable. 

SARS-CoV-2 without background

Spike Protein

Overall, there is much promise but also notable concerns to the new drug Molnupiravir. I believe that this new medicine, even with its downsides, could save hundreds of thousands of lives. As Ms. Saey states, “a 30 percent reduction in hospitalizations and deaths is worth giving the drug temporary authorization.”

Can Fruit Flies Really Help Cancer Research?

Fruit fly (7424411436)In a study conducted at the University of California, Berkeley, researchers identified similarities between fruit flies and humans with cancer and believe this research could lead to prolonging the lives of cancer patients. Cancer, a disease where cells “grow uncontrollably and spread”, was diagnosed in 18.1 million new cases and claimed the lives of 9.5 million new patients worldwide as recently as 2018. The Berkeley researchers took a new approach to tackle cancer by “launching an attack against the destructive chemicals cancer is throwing off.” They believe this new method could increase patients’ survival rate and overall health.

David Bilder, a UC Berkeley professor, stated that the goal of the research was “to help the host deal with the effects of the tumor, rather than killing the tumor itself”; this represents a different approach to cancer treatment since most current treatments focus on killing the tumor and the unhealthy cells. Conventional treatments create serious side effects in patients as the treatments impact healthy cells too. Bilder’s research attempts to interfere with the blood-brain barrier, a feature of the central nervous system which is key in regulating microorganism entry and exit from the bloodstream and interstitial brain fluid. It is believed that inflammation caused by tumors leaves the blood-brain barrier open, but interfering with that process might slow tumor growth allowing for improved patient quality of life and life expectancy. This process could eliminate the need for toxic drugs that harm healthy cells while targeting cancer cells.

During the research a few years ago, Bilder’s team also learned some interesting new information about the impact of insulin on cancer. They concluded that tumors in fruit flies release a substance that blocks the effects of insulin. Insulin, a type of protein that coordinates organism activities while maintaining normal blood glucose levels, is a crucial component of our body system. It allows cells to absorb glucose which can serve as energy or convert to fat if necessary. Without insulin, cells are unable to use glucose as fuel and bodies would start breaking down their fat and muscle resulting in weight loss. This can pose an issue because it could lead to cachexia (an effect of cancer where patients are unable to maintain weight) which sadly kills ⅕ of cancer patients. Although more research is needed to investigate the relationship between insulin and cancer in humans, sugar may play a role in the growth of cancer.

 

CSIRO ScienceImage 355 Representation of Insulin Structure

Insulin Structure

I believe that this new approach to cancer treatment is a fascinating angle to effectively treat cancer patients. As someone who has experienced cancer in two close family members, I know firsthand how draining the treatments are because they target healthy cells as well as cancerous ones; this treatment simply diminishes these side effects. As Bilder states, “We think this is a real blind spot that hasn’t allowed scientists to address questions about how the tumor is actually killing outside of its local growth.” It could offer a “complementary way of thinking about therapy.” It is great to see new ways of thinking address a disease that impacts so many people.

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