BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: Mutation

Can this Protein Cause Alzheimer’s?

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On October 20, 2022

In Student Post

What causes Alzheimer’s? Initially, one might think that it is a result of age-related changes in the brain or environmental and lifestyle changes. One may also think that it is caused by a genetic predisposition to the disease. Personally, I thought Alzheimer’s was a result of poor health as one got older. Although these all may be true, a new study has found that Alzheimer’s Disease can be caused by a certain protein, or rather, a protein mutation. These new findings provide scientists with a way to detect and treat the disease in the long run.  Using multiple methods to analyze mitochondrial DNA, researchers found a mitochondria microprotein that is associated with Alzheimer’s Disease. This protein, known as SHMOOSE is seen to have a role in the neurodegeneration of people, thus giving them an increased chance of Alzheimer’s Disease. Furthermore, the researchers found that the microprotein is found in over a quarter of Europeans. The researchers of The Cohen Laboratory at the University of Southern California published their findings in the journal of Molecular Psychiatry. The journal states that the microprotein, SHMOOSE was discovered through the use of neuroimaging, mass spectrometry, and transcriptomic. All of these are methods of looking into the mitochondrial DNA and locating the mutated protein. According to the study, a mutation of the SHMOOSE microprotein has a connection to a higher risk for Alzheimer’s Disease. They also discovered that 25% of individuals with European ancestry have the mutated version of the protein. Dr. Pinchas Cohen says that the SHMOOSE mutation is a result of a single nucleotide polymorphism or SNP. An SNP is essentially a change or alteration within a single nucleotide, in this case, the change resulted in the mutated SHMOOSE protein. Additionally, he states that the variant can guide ways to identify who is affected while also forming new medical treatments and preventative measures. In class, we learned about how proteins are created and coded for, and we also learned about how protein structure directly affects their function. Both of these concepts are directly seen in this study. Firstly, DNA is what codes for proteins, if the DNA or even the nucleotide is incorrect or altered, the protein would in turn also be incorrect or altered. This is seen directly through the SNP, the single change in the nucleotide entirely changed the protein creating the SHMOOSE protein. Next, the structure of the protein, the sequence of the amino acids, or just the overall composition of the protein entirely plays a role in the function and actions of the protein. For example, if the structure of a protein is compromised, so is the function. This is also directly seen in the study because the structure of the SHMOOSE protein was altered due to the SNP, its function was also altered. The altered function is that it would put people at a higher risk for Alzheimer’s Disease. Another article speaks on the silver lining of the SHMOOSE protein. Because the protein is the approximate size of an insulin peptide, it could easily be administered into the human body for a positive effect. This means that the mutated protein could be used for treating Alzheimer’s Disease and increasing its therapeutic value. This idea is just one of many that venture into the field of precision-based medicine. In the case of Alzheimer’s the mutated SHMOOSE would be focused upon as a target area rather than the disease as a whole. I think that the use of SHMOOSE in a medical or therapeutic way would be risky at first in that it would likely be difficult for scientists to specifically target the way to treat it. What may be a safer option for those with the mutation could be to continue with tried and tested Alzheimer’s Disease treatments rather than immediately opting for something new. The new precision-based medicine method should undergo severe trials, examinations, and successes before it is widely implemented.

 

Noun Alzheimer Nithinan 2452316

 

CRISPR Mini | New Territory Unlocked

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On March 20, 2022

In Student Post

For over a million years, DNA has centered itself as the building block of life. On one hand, DNA (and the genes DNA makes up) shapes organisms with regard to physical appearance or ways one perceives the world through such senses as vision. However, DNA may also prove problematic, causing sickness/disease either through inherited traits or mutations. For many years, scientists have focused on remedies that indirectly target these harmful mutations. For example, a mutation that causes cancer may be treated through chemotherapy or radiation, where both good and bad cells are killed to stop unchecked cell replication. However, a new area of research, CRISPR, approaches such problems with a new perspective.

The treatment CRISPR arose to answer the question: what if scientists could edit DNA? This technology involves two key components – a guide RNA and a CAS9 protein. Scientists design a guide RNA that locates a specific target area on a strand of DNA. This guide RNA is attached to a CAS9 protein, a molecular scissor that removes the desired DNA nucleotides upon locating them. Thus, this method unlocks the door to edit and replace sequences in DNA and, subsequently, the ways such coding physically manifests itself. Moreover, researchers at Stanford University believe they have further broadened CRISPR’s horizon with their discovery of a way to engineer a smaller and more accessible CRISPR technology.

This study aimed to fix one of CRISPR’s major flaws – it is too large to function in smaller cells, tissues, and organisms. Specifically, the focus of the study was finding a smaller Cas protein that was still effective in mammalian cells. The CRISPR system generally uses a Cas9 protein, which is made of 1000-1500 amino acids. However, researchers experimented with a Cas12f protein which contained only 400-700 amino acids. Here, the new CasMINI only had 529 amino acids. Still, the researchers needed to figure out if this simple protein, which had only existed in Archaea, could be effective in mammals that had more complicated DNA.

To determine whether Cas12f could function in mammals, researchers located mutations in the protein that seemed promising for CRISPR. The goal was for a variant to activate a protein in a cell, turning it green, as this signaled a working variant. After heavy bioengineering, almost all the cells turned green under a microscope. Thus, put together with a guide RNA, CasMINI has been found to work in lab experiments with editing human cells. Indeed, the system was effective throughout the vast majority of tests. While there are still pushes to shrink the mini CRISPR further through a focus on creating a smaller guide RNA, this new technology has already opened the door to a variety of opportunities. I am hopeful that this new system will better the general well-being as a widespread cure to sickness and disease. Though CRISPR, and especially its mini version, are new tools in need of much experimentation, their early findings hint at a future where humans can pave a new path forward in science.

What do you think? Does this small CRISPR technology unlock a new realm of possibility or does it merely shed light on scientists’ lack of control over the world around us?

Changing Composition of SARS-CoV-2/Understanding the Alpha Variant in England

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On January 4, 2022

In Student Post

Since its emergence in the Fall of 2020, the original SARS-CoV-2 variant of concern (VOC) rapidly became the dominant lineage across much of Europe. Although, simultaneously, several other variants of concern were identified globally. Like B.1.1.7 or the Alpha Variant (first mutation of SARS-CoV-2 found to be more transmissible), these VOCs possess mutations thought to create only partial immunity.

Researchers are understanding when and how these additional VOCs pose a threat in settings where B.1.1.7 is currently dominant. This is where scientists in the UK examined trends in the prevalence of non-B.1.1.7 lineages in London and other English regions using passive-case detection PCR data, cross-sectional community infection surveys, genomic surveillance, and wastewater monitoring. The study period spanned from January 31st of 2021 to May 15th of 2021.

Through this data, the percentage of non-B.1.1.7 variants has been increasing since late March 2021. This increase was initially driven by a variety of lineages with immune escape. From mid-April, B.1.617.2 (WHO label of Delta) spread rapidly, becoming the dominant variant in England by late May, similarly to the Alpha Variant.

Shown by many mutations in the spike protein receptor (RBD), studies suggest B.1.1.7 is 50–80% more transmissible with greater severity than previously circulating Covid Variants. B.1.1.7 rose rapidly, from near 0% to over 50% in under two months, and soon made up greater than 98% of sequenced samples in England. Its rapid spread necessitated a third lockdown in England during last January. Subsequent spread in Europe and North America has highlighted the threat this variant poses to a continued alteration of the Coronavirus.

The 69–70 deletion in B.1.1.7′s Spike gene causes PCR tests to return negative results for that gene target which is a major problem when identifying and testing for Covid. One of the most important changes in lineage of B.1.1.7 seems to be a spike protein substitution of N501Y, a change from asparagine to tyrosine in amino-acid position, that enhances transmission. These alterations can change antibody recognition while also affecting ACE2’s (receptor protein) binding specificity which can then lead to the virus becoming more infectious. We are seeing a pattern of the same type of mutation in Covid consistently.

An example of a similar mutation that has been recent is the new Omicron variant out of South Africa. Omicron is similar in which their has been a specific change in the spike protein where antibody recognition is limited and it is highly transmissible between any living organism. Our class has understood and studied the importance of our body being able to identify and create an antibody for the specific antigen being displayed by a pathogen.  These mutations within the spike protein allow another immune response to happen which a different antibody has to be created to mark the different antigen being displayed. Unfortunately, this will be a continuing problem without vaccine mandates since it gives the virus more time to mutate where outbreaks like in South Africa will continue to transpire around the world.

Embryo Gene Editing can Ensure Offspring Do Not Inherit a Deafness Gene!

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On January 23, 2020

In Student Post

Denis Rebrikov, A scientist in Russia has done research regarding ways in which he can edit the genome sequence of an embryo in order to prevent the fetus from developing certain gene mutations, specifically in this case a hearing problem or possible complete deafness. His plans are very controversial to some, who believe the possible risks of very harmful mutations to DNA that would be passed onto direct and future offspring, outweigh the possible benefits. However, some people find this scientific possibility to be worth the risk, if it means not passing a potentially very harmful gene down to offspring. If these methods are done correctly, it should alter the genome sequence in the embryo so that future offspring off that embryo will not inherit the negative mutation.

One couple shared their story in detail, in which both parties have a hearing deficiency, the man with partial deafness, and the woman completely deaf. Their biggest hope is to have children who will not inherit hearing issues, because of the apparent challenges they have had to face themselves because of them. They would be the first couple to perform this gene editing on an IVF embryo, so they obviously have some reservations. One of those being publicity, but more importantly the potential risks of using the CRISPR genome editor. They already have a daughter with hearing loss, but they never chose to test her genes for mutations, nor did they get her a cochlear implant to aid her hearing, because of the potential risks of that. When they finally tested her genes, they learned that she had the same common hearing loss mutation called 35delG in both her copies of a gene called GJB2. The parents then tested themselves, realizing they were both 35delG homozygous, meaning their daughter’s mutations were not unique to her, they had been inherited.

If either the mother or father had a normal copy of the GJB2 gene, a fertility clinic could have more easily created embryos by IVF and tested a few cells in each one to select a heterozygote–with normal hearing–to implant. At this stage, Denis Rebrikov informed them that CRISPR genome editing would be their only option. However, the process presents possibly deal breaking risks, such as mosaicism, in which a gene edit might fail to fix the deafness mutation, which could create other possible dangerous mutations like genetic disorders or cancer. The couple has not decided to go through with the editing just yet, but it is something they are open to in the future as more possible new research or test subjects become available.

Explaining the CRISPR Method: “The CRISPR-Cas9 system works similarly in the lab. Researchers create a small piece of RNA with a short “guide” sequence that attaches (binds) to a specific target sequence of DNA in a genome. The RNA also binds to the Cas9 enzyme. The modified RNA is used to recognize the DNA sequence, and the Cas9 enzyme cuts the DNA at the targeted location… Once the DNA is cut, researchers use the cell’s own DNA repair machinery to add or delete pieces of genetic material, or to make changes to the DNA by replacing an existing segment with a customized DNA sequence.” -US National Library of Medicine Genetics Home Reference

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Woman with a hearing aid 

If you had the opportunity to alter something in the gene’s of your baby’s embryo, would you? Under what circumstances would you consider this, and what risks might stop you from deciding to do it? Comment down below.

 

 

A Gene Mutation that Keeps You Awake and Functioning for Longer

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On October 27, 2019

In Student Post

INTRODUCTION:

Could a gene mutation really allow someone to finish college in two and a half years? The answer is yes! We all wish we could get by a function perfectly, or even better than normal, on less sleep. This is a reality for some, specifically people with a rare gene mutation. I saw an article titled, “Why Do Some People Need Less Sleep? It’s in their DNA,” and I thought this was a rather interesting topic, because I have never heard of less sleep ever being a positive thing. I am interested to see more research on this, and the possibility of it being an added benefit for others. It prompted me to think about whether or not this is something I would want, considering some of the implications. 

People with this gene mutation can get significantly less sleep than recommended for function, as little as three to four hours—without suffering any health consequences and while actually performing on memory tests as well as, or better than, most people. There is now a new study correlating to a new genetic mutation found with these “powers,” after previous studies revealed other types of mutations that may impact sleep.

 

HOW DID IT START?: 

To understand this rare ability when presented to them, scientist Ying-Hui Fu and her team, at the University of California, San Francisco, in 2009, began this study on some individuals, but also on mice, to simulate a similar sleep equilibrium to humans. After a woman came in claiming she was functioning at a high level on very short sleep time, scientists needed to understand, as lack sleep is typically correlates with health issues such as risk of heart attack, cancer, or even Alzheimer’s. They initially found a small mutation in the DEC2 gene, a transcriptional repressor (hDEC2-P385R) that is associated with a human short sleep phenotype. According to UCSF, DEC2 helps regulate “circadian rhythms, the natural biological clock that dictates when hormones are released and influences behaviors such as eating and sleeping. This gene oscillates this particular c schedule: rising during the day, but falling at night.” The newer study reveals that the DEC2 gene lowers your level of alertness in the evening by binding to and blocking MyoD1, a gene that turns on orexin production, a hormone involved in maintaining wakefulness. Fu says the mutation seen in human short sleepers weakens DEC2’s ability to put the breaks on MyoD1, leading to more orexin production and causing the short sleepers to stay awake longer.

THE NEW GENE MUTATION: 

In a new study, released on October 16, 2019, by Science Translational Medicine brought on by a mother and daughter duo, mice were studied again to mimic the human sleep pattern. The mice again required less sleep, and were able to remember better. In the study, researchers identified a point mutation in the neuropeptide S receptor 1 (NPSR1) gene responsible for the short sleep phenotype. The mutation increased receptor sensitivity to the exterior ligand, and mice with the mutation displayed increased mobility time and reduced sleep duration. Even more interestingly, the animals were resistant to cognitive impairment induced by sleep deprivation. The results and findings in the study point to NPSR1 playing a major role in sleep-related memory consolidation. NSPR1 is a gene that codes for a brain receptor that controls functions in sleep behaviour and awakeness. In the new study, when mice were given this gene mutation, there were no obvious health, wellness, or memory issues over time. Although the family members did not appear to experience any of the negative effects of sleep deprivation, the researchers make sure to emphasize that longer term studies would be needed to confirm these findings.

WHAT DOES THE FUTURE HOLD?: 

In the future, a possible drug could be produced to synthesize a change in one of these genes, as a possible treatment for insomnia or other sleep disorders. We would need a lot more research about their functions, though, because of possible negative neurological side effects. 

If a medication with these powers were to exist, do you think it would cause social issues regarding some  possibly forcing certain individuals to take it to work longer hours/get more done? Do you think that it should be available to everyone, or only people with certain conditions? Comment about this below. 

 

Could CRISPR Cure Duchenne Muscular Dystrophy?

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On March 7, 2018

In Student Post

What is Duchenne Muscular Dystrophy?

https://www.flickr.com/photos/150276478@N03/34406844136

Duchenne muscular dystrophy, DMD, is an X-linked recessive disease caused by defects in the gene that makes the dystrophin protein. This particular gene is made of 79 exons, and the defects can occur on any of them. These defects lead to degeneration of skeletal and heart muscle, forcing patients to rely and wheelchairs and respirators. Without a cure, most people with the disease die by the age of 30. So, the question becomes, how can we find a cure?

What is Precision Editing?

http://www.njsta.org/news/crispr-in-the-classroom-by-simon-levien

CRISPR technology has advanced tremendously in the past several years, with each study building off the last. CRISPR technology has the capability to cut out segments of DNA, but with the risk of cutting out too much or the wrong parts. Thus, it is crucial that the cutting be as precise as possible. The CRISPR-Cas9 gene-editing tool, uses an RNA strand to guide the Cas9 enzyme along the DNA strand, skipping over important “healthy” DNA and leading the enzyme to cut a specific portion of DNA.

 How do DMD and Precision Editing Connect?

Dr. Olsen is Co-Director of the Wellstone Muscular Dystrophy Cooperative Research Center, a lab in which a team has been working to apply precision editing to DMD. The method uses one single cut of DNA along strategic points and is less intrusive than other methods. Scientists have developed guide RNAs with the purpose of finding mutation “hotspots” along the dystrophin gene. The RNA strand guides the Cas9 enzyme to 12 regions where most DMD mutations have been found. According to the article, “the new strategy can potentially correct a majority of the 3,000 types of mutations that cause DMD.” Wow! In a recent study using this method, these RNAs helped rescue cardiac function to near-normal levels in human heart muscle tissue.

Why is it Important?  

The new study demonstrates eliminating abnormal splice sites in human DNA can correct a wide range of mutation. In the case of DMD, the splice sites that were removed using CRISPR technology instruct the genetic machinery to build abnormal dystrophin molecules. Once these sites are removed, an improved dystrophin protein was observed. Even more fascinating, correcting only half of the damaged cells restored cardiac function to a healthy level. Does this sound fascinating? If you answered yes, click here to learn more!

What Does the Future Hold?

The strategy of single-cut editing may be useful for treating other single-gene diseases. News of such prospects has generated a great deal of hope for patients. Much more research is needed before CRISPRCas9 can be used on human patients. Labs and researchers around the world are working to perfect this method so that it can get federal government approval and move to the next stage – human trials. As research progresses, it will be faced with backlash from some who believe DNA should not be altered and that the technique is too risky and support from those who believe this new technique could save lives. Which side do you fall on?

New Research Sheds New Light on Cancer Preventing Proteins

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On November 18, 2015

In Student Post

Cells in the human body are constantly dividing. Whenever cells divide into two, the DNA within them must be copied as well. Most of the time this process works as planned, but some times the DNA can be copied incorrectly. Other factors such as UV rays and radiation can damage DNA and lead to problems like cancer. While these errors in DNA copying can cause significant mutations, they are usually corrected by certain proteins within the cell. New research at the University of Michigan is allowing scientists to get a better idea of how these proteins go about finding the damaged sites and repairing them.

Mutación ADN

Image Source

In this study, researchers at UM examined the MutS protein in bacteria. According to Lyle Simmons, associate professor of molecular, cellular, and developmental biology at UM, it has been known for a long time that the MutS protein could find and repair errors in DNA. “MutS is the first protein involved in DNA mismatch repair and is responsible for detecting rare errors that can predispose people to certain types of cancer, a hereditary condition called Lynch syndrome or cancer family syndrome. If a person’s mismatch repair system is hindered, the mutation rate increases 100-to-1,000 fold” says Simmons.  Despite knowing what these proteins do, it remained unclear as to how they perform these tasks.

To see how the protein works, researchers “fused the MutS protein to a fluorescent tag and activated fluorescence with a laser.” They then studied the protein’s actions inside of a bacterial cell. Tagging the proteins with fluorescence allowed researchers to track its movement through the cell. Scientists observed that MutS moved quickly through the nucleoid but slowed down at DNA replication sites. This indicates that the proteins look for sites of replication rather than individual mismatches. The protein then searched the new DNA being created for errors. Mismatches occur when the wrong nitrogenous bases are paired with each other. “The mismatched pair kinks the DNA at the replication fork where DNA is made. MutS positions itself at that fork so it’s ready to catch any mistakes. As an added bonus, this positioning likely tells MutS which side is correct and which side is the new, altered DNA.” says Julie Biteen, assistant professor of chemistry.

Despite the study being performed on bacteria, it is very likely that the same process occurs in human cells.  This discovery is very important because it provides information that will be essential to learning more about how the body responds to mutations.  Further advances in this area of study could possibly help researchers understand cancer better.

Original Article

The mutation and spread of Cancer caused by changes in Epigenetics

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On March 8, 2015

In Student Post

Epigenetics could be the key to understanding how cancer originates, when it mutates, and how it spreads. Researchers at the Boston University School of Medicine (BUSM) believe that different types of cancer are caused by an “on and off” switch in the epigenome. While many scientists believe  that many cancers originate in cells called progenitor cells, they cannot concoct a model that explains  how cancer spreads from the progenitor cell and mutates into many forms as it continues to grow in a person’s body.

One of the lead researchers, Sibaji Sarkar, posited “there should be a general mechanism that initiates cancer progression from predisposed progenitor cells, which likely involves epigenetic changes.” The researchers believe that the theory of an epigenetic switch is supported by the growth of tumors, which go through many different stages. The team believes that if cells can be altered to become cancerous and remain stuck in their stage of growth while they replicate out of control, then there must also be an off switch to this uncontrolled replication. They also suspect that epigenetic changes can determine the rapidity of growth and the mutability of the characteristics of the cancer and tumors.

Although Sarkar’s team has not yet found specific epigenetic code that causes these mutations and growth, he believes that their hypothesis will cause other scientists to focus their attention on the epigenome and find ways to prevent progenitor cells from spreading and mutating into malignant tumors.

This epigenetic research relates to our study of the relationship between the epigenome and cancer. Specifically the absence of an active p53 protein would prevent a certain part of the DNA from being  read and the cell would therefore lack a protein that inhibits the cell cycle. This would cause uninhibited cell division and the spread of cancer.

 

Methylation of DNA

640px-DNA_methylation

How the “guardian of the genome” falls:

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On February 10, 2013

In Student Post

 

 

 

p53 is a protein that plays a vital role in the G2 checkpoint phase before mitosis begins. This checkpoint “ serves to prevent the cell from entering mitosis (M-phase) with genomic DNA damage.” (http://www.cellsignal.com/reference/pathway/Cell_Cycle_G2M_DNA.html) The role of p53 is to trigger repair for damaged DNA if possible and to hold the cell in the G1/S checkpoint until it is repaired and if the repair of the DNA is not possible p53 triggers apoptosis. Therefore, p53 plays a large role is preventing cancer because a cancerous cell starts with a mutation in DNA.  However mutant p53 allows cells who have DNA damage and have “tranformed” to be cancerous to enter into M-phase and proliferate thus forming a tumor.

Biologists, chemists and computer scientists at UC bolder however have discovered a “an elusive binging pocket” in the quaternary structure of p53 which is open “5 percent of the time.” (http://www.sciencedaily.com/releases/2013/01/130131121312.htm) The reason the pocket is only open 5 percent of the time is because the p53 protein undulates, meaning it sways so this pocket was hard to find and target. Their team then screened almost 2,500 molecules and tested out 45 molecules to see if any of them could fit into this pocket and trigger the normal tumor-suppressing abilities found in p53 in a mutated p53 molecule. They found that stictic acid fit and triggered the tumor-suppressing abilities. Although stictic acid is not able to be used as a drug, they can now scan other molecules that have similar properties as stictic acid making this a large step in cancer research because mutated p53 is found in over 40 percent of diagnosed cancer cases. (http://www.sciencedaily.com/releases/2013/01/130131121312.htm)

 

Sources:

http://www.sciencedaily.com/releases/2013/01/130131121312.htm

http://www.cellsignal.com/reference/pathway/Cell_Cycle_G2M_DNA.html

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