BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: DNA (Page 1 of 5)

A New Way to “Tangle” with Diseases? British Scientists Think They’ve Stumbled Upon the Future

A team of scientist from the Universities of Bath and Birmingham have made a discovery that is making noise in the world of Biology. Ironically, they had the realization while studying silent mutations in DNA. What they found is a new method of evolution. Well not a new method per say as the scientists predict this method is being used in all forms of life; however, new in the sense that it was only recently realized. What they have discovered is a trend of tangles in DNA strands. This tangling occurs in DNA strands that are not in a double helix as DNA typically is. However The DNA strands are separated during copying. This task is done by DNA polymerase enzymes. During the copying process, the enzymes are often disrupted by the tangles in the strand. The resulting skipping of genes causes specific mutations to the DNA.

DNA replication split horizontal

The scientists then tested their hypothesis by way of experiment. They did so by studying the evolution of soil bacteria called Pseudomonas fluorescens (SBW25 and Pf0-1). They began by removing the gene that give the bacteria the ability to swim. They then observed the re-evolution of the strains to regain the ability swim. Both strains evolved quickly; however, there was a clear differences in predictability. One strain (SBW25) mutated the same part of a particular gene in every trial. The other strain (Pf0-1) varied in which gene and where the mutation occurred in each trial. Upon further observation, this contrast coincided with a hair-pin shaped tangle in the SBW25 strain. As the DNA polymerase enzymes would pass this tangle they would be effected in a predictable manner that would disrupt copying of DNA and result in a mutation that allows for the bacteria to swim. The scientists tested the theory by removing the tangle. They did so using 6 silent mutations so that the DNA sequence would not have a relevant change. The trials after the change showed that both strains showed inconsistent areas being mutated.

 

DNA are the dictators of protein synthesis in the body. The DNA sequences code for the types of proteins that are created. Proteins perform many of the bodies function. This means that even the slightest change in the sequencing of DNA can have major effects on the functioning of a human body or any organism. The process of evolution was thought to be caused by random errors in DNA sequencing that coincidentally gave an organism a survival advantage. These mutations would then be tested in the concept of survival of the fittest. While this is still thought to be the most prevalent form of evolution, especially with eukaryotic organisms, the tangling of DNA strands proposes a form of evolution that would be easier to study and predict.

 

The predictability of such a phenomenon is where the intrigue in viruses arises. “If we knew where the potential mutational hotspots in bacteria or viruses were, it might help us to predict how these microbes could mutate under selective pressure.” says Dr. Tiffany Taylor, from the Milner Centre for Evolution. Mutational hotspots have already been found in cancer, and the new information on their significance is getting scientists excited about the opportunities present. The new ways to understand and predict evolution of bacteria and viruses may allow scientists to be a step ahead on vaccines and be able to anticipate and understand new variants. It’s hard not to think this information would’ve been nice before the rise of SARS-CoV-2.

Is Junk DNA Really Junk?

DNA is the base code of all living creatures. It is in every plant, animal, and single-cell organism, yet  50% of human DNA is seen to be irrelevant to bodily function. While some DNA is responsible for synthesizing materials within cells, much of it is in essence, spare genes, or ancient viruses that have become part of the human genome over time. Moreover, it has been debated whether the 50% of DNA that is not seen to be relevant is truly essential for survival. That is, can humans live without unused genetic code, or is it vital to the survival of the species?

Ácido desoxirribonucleico (DNA)

One specific element of junk DNA is transposons. Transposons are sequences of DNA that have the ability to mutate a cell or change its function as a whole. A study was conducted at the University of California, Berkley, and Washington University on transposons, as written in the So-called Junk DNA – Genetic “Dark Matter” – Is Actually Critical to Survival in Mammals, by the University of California, Berkley. The studies looked at a specific transposon in mice called MT2B2, one that controlled the growth rate of cells in a fertilized embryo, and when the embryo would implant in the uterus of the mother by initiating the short gene Cdk2ap1. When the researchers disabled the MT2B2 transposon using CRISPR-EZ, the mice created a longer version of the gene Cdk2ap2. This new version of the gene decreased cell growth and increased the period of implantation. The teams found that half of the baby mice died before birth without this transposon in their DNA. When the transposon was disabled, the mice sort randomly instead of uniformly in the uterus, and some may cause the death of a developed fetus and or the mother.

The team at Washington University researched the transposons turned on before embryos are impacted into the uterus in humans, rhesus monkeys, marmosets, mice, goats, cows, pigs, and opossums. The team used scRNA-seq, which records messenger RNA levels to indicate which genes are being used. With this technique,  the team saw that in every animal, a group of species-specific transposons was turned on. While the transposons were different for each species, the result of their use was nearly the same for all eight cases. Moreover, the gene Cdk2ap1 was expressed by all eight animals, but the amount of short and long versions of the gene expressed was unique for each one. While an animal that needs fast implantation uses more of the short version of the gene, like the mouse, animals with little to none of the shorter version of Cdk2ap1 took two weeks to longer for implantation to occur, like the cow.

Baby Mouse Rehabber

For these transposons to be promoting the expression of the Cdk2ap1 gene, at a certain point in history, a virus entered the organism and eventually part in a mutually beneficial symbiotic relationship with the organism until it evolved into the current iteration of the transposon. When viruses blend into the DNA of a species, they can be used to regulate and perform tasks that the cell could not previously perform. This can create a wide range of evolutionary options in species. Additionally, the main difference between the different genomes of species is the regulation of genes. By studying transposons, scientists can better understand differences in the genome of one species to another. With the understanding of this transposon, scientists could now begin searching further into junk DNA, as the removal of the transposon studies by the two universities proved lethal 50% of the time. Moreover, undiagnosed patients could have junk DNA mutations that lead to health problems, but those cases are currently a mystery to the medical world. Transposons are just the beginning of scientists dive into junk DNA, and who knows what wonders they will find next?

“I Wanna Live Forever Young”

Aging: the inevitable… or so we thought. Don’t get too excited, aging is apart of every living organisms’ life, and it always will be. Besides growing old as a downside itself, the real worry of aging is all of the diseases that you grow prone too. But what if there was a way to change that? What if there was a way to grow old healthily? In this blog post, I am going to be explaining how cellular modifications can potentially change the future of aging forever.

In order to understand how to prevent aging, we must understand how aging occurs in the first place. One of the main causes of aging roots from the mitochondria. The mitochondria is the source of energy for the cell and is responsible for cellular respiration. It also is independent from the cell, so it has its own DNA known as mtDNA. As time goes on, exposure to toxic products within the cell begins to cause the mitochondria’s DNA (mtDNA) to mutate. The build up of this mutation in mtDNA eventually causes the cell to function improperly, causing respiratory chain disfunction and many cell degenerative diseases. Common diseases due to mtDNA mutations are Parkinson’s disease, Alzheimers, and Huntington’s disease. Mitochondrial dysfunction can also lead to the damaging of nerve function- another side effect of old age. In our AP Biology class, we learned about the significant role the mitochondria has on cell function and how it came to be apart of the cell through the Endosymbiont Theory. This theory mentions the mitochondria’s own DNA, which we are diving into today to understand the effects of genetic mutation in the mitochondria and how we might combat it.

Mitochondrion (standalone version)-en

 

Professor and disease research specialist Ming Guo dives into how we can achieve healthier aging by combating mtDNA mutation. The only way to do this would be to rid the cell of mutant mtDNA and restore mitochondrial function. In order to understand how to do this, Guo conducts an experiment with Professor Bruce Hay involving fruit flies. Fruit flies share 80% of their disease genetics with humans, making them a viable option to begin testing on. Guo observed that by forcing the cell into autophagy, the cell will remove damaged cell parts and therefore restore proper cell function. By starving the cell, the cell is forced to eat damaged parts of itself, including mutated mitochondrial DNA, in order to survive. The term “autophagy” can be broken in to two terms: “auto” and “phagy”. “Auto” refers to “self” and “phagy” means “eat”. In essence, autophagy means, “self eating”, as seen through the cells digestion of its own damaged parts. This gets inevitably prevents mutations of the cell that damage cognitive function and mobility that usually come with old age. In our AP Bio class, we also discussed autophagy, or the removal of waste from a cell through the use of lysosomes.

The findings of this study shed light on how to counter mtDNA mutation through triggering cellular processes, such as autophagy, at a more efficient level than the cell previously had.  On average, triggering autophagy in a cell gets rid of 95% of its mutated mitochondrial DNA. Guo and Hay’s findings are only just the beginning. Now that it is understood how to prevent mitochondrial DNA mutation, scientists must discover specific drugs on how to activate the cellular processes in a way that is safe, easy to administer, and available to the public. The answer to healthy aging, and longer lasting cognitive function that goes with it, is just around the corner!

I chose this topic because aging is inevitable for everybody, therefore it is relevant to every single person. Also, being that my family has a history with age related diseases, this topic particularly interests me. Ever since I was a kid, I would hear things like “You’ll be able to live to 200 the way technology is advancing” all of the time. This discovery is a huge step on making that statement a reality. Hopefully aging will soon become a less dreadful concept and people will live to be happier and healthier.

 

 

 

 

Your Inner Chimpanzee

 

Chimpanzees

What is the closest living relative we have (evolutionary speaking)? That’s right, chimpanzees!! Our evolutionary paths separated us about five to six million years ago leading to the chimpanzee of today, and us humans of the 21st century, but we still have much in common. Like humans, Chimpanzees use body language to communicate. They often kiss, hug, pat each other on the back, hold hands and shake their fists. They even laugh when they get tickled. At the same time, a lot has also changed. Not only do we stand on two legs and are relatively hairless, but we also have brains that function differently. 

 

Recent research from Lund University has found the answer to what in our DNA makes our brains different. Created by Shinya Yamanaka, the study used a revolutionary stem cell technique. Yamanaka discovered that if reprogrammed specialized cells can be developed into all types of body tissue. It was even recognized by the 2012 Nobel Prize in Physiology or Medicine. 

 

The researchers used stem cells grown in a lab. Their partners in Germany, the US, and Japan reprogrammed the skin cells. Then Johan Jakobsson, professor of neuroscience at Lund University, and his partners examined the stem cells that they had developed into brain cells. Using the stem cells, the researchers specifically grew brain cells from humans and chimpanzees and compared the two cell types. The researchers then found that humans and chimpanzees use a part of their DNA in different ways. This appears to play a significant role in the development of our brains.

 

What the researchers learned was different in part of our DNA they and I found so unexpected. Unlike previous research in the part of the DNA where the protein-producing genes are — about roughly two percent of our entire DNA, the difference that was found indicated that the differences between chimpanzees and humans appear to lie outside the protein-coding genes. The research found that it is actually located a so-called structural variant of DNA in what has been labeled as “junk DNA,” a long repetitive DNA string that has long been deemed to have no function. This was thought to have no function. 

 

This data suggests that the basis for the human brain’s evolution is a lot more complex than previously throughout genetic mechanisms, as it was supposed that the answer was in that 2 percent of the genetic DNA. These results indicate that the overlooked 98 percent is what has been significant for the brain’s development is instead perhaps hidden in, which appears to be important. 

 

Researchers hope to answer that question one day. But there is a long way to go before they reach that point. The question that now remains is instead of carrying out further research on the two percent of coded DNA should they delve deeper into all 100 percent. Even though exploring the missed ninety-eight percent is a considerably more complicated task for research. 

 

One question that also definitely still remains is why did the researchers want to investigate the difference between humans and chimpanzees in the first place?  

 

Well, Johan Jakobsson believes that in the future the new findings will prove his belief that the brain is the key to understanding what it is that makes humans human. How did it come about that humans can use their brains in such a way that they can build societies, educate their children and develop advanced technology? It is fascinating!” (Lund University). He hopes that this research will contribute to answers about things like genetically-based questions about psychiatric disorders, such as schizophrenia. As for me, I wonder if this continued research will tell us anything about how Chimpanzees will evolve. 

 

 

Mutation in the Nation

We constantly think of SARS-CoV-2, the virus that causes COVID-19, as a single virus, one enemy that we all need to work together to fight against. However, the reality of the situation is the SARS-CoV-2, like many other viruses, is constantly mutating. Throughout the last year, over 100,000 SARS-CoV-2 genomes have been studied by scientists around the globe. And while when we hear the word mutation, we imagine a major change to how an organism functions, a mutation is just a change in the genome. The changes normally change little to nothing about how the actual virus functions. While the changes are happening all the time since the virus is always replicating, two viruses from anywhere in the world normally only differ by 10 letters in the genome. This means that the virus we called SARS-CoV-2 is not actually one species, but is a quasi-species of several different genetic variants of the original Wuhan-1 genome.

The most notable mutation that has occurred in SARS-CoV-2 swapped a single amino acid in the SARS-CoV-2 spike protein. This caused SARS-CoV-2 to become significantly more infective, but not more severe. It has caused the R0 of the virus, the number of people an infected person will spread to, to go up. This value is a key number in determining how many people will be infected during an outbreak, and what measures must be taken to mitigate the spread. This mutation is now found in 80% of SARS-CoV-2 genomes, making it the most common mutation in every infection.

Glycoproteins are proteins that have an oligosaccharide chain connect to them. They serve a number of purposes in a wide variety of organisms, one of the main ones being the ability to identify cells of the same organism.  The spike protein is a glycoprotein that is found on the phospholipid bilayer of SARS-CoV-2 and it is the main tool utilized in infecting the body. The spike protein is used to bind to host cells, so the bilayers of the virus fuse with the cell, injecting the virus’s genetic material into the cell. This is why a mutation that makes the spike protein more efficient in binding to host cells can be so detrimental to stopping the virus.

In my opinion, I find mutations to be fascinating and terrifying. The idea that the change of one letter in the sequence of 30,000 letters in the SARS-CoV-2 genome can have a drastic effect on how the virus works is awfully daunting. However, SARS-CoV-2 is mutating fairly slowly in comparison to other viruses, and with vaccines rolling out, these mutations start to seem much less scary by the day.

 

What is Nanotechnology, and How is it Transforming Vaccine Development for SARS-CoV-2?

1,000+ Free Covid-19 & Coronavirus Illustrations - PixabayCOVID-19 Spike Protein

In an era of mask-wearing and social distancing, the big question on everyone’s mind is when will things go back to normal? Scientists all over the world have been working quickly and intensely to develop a solution–one that is safe. 

Nanotechnology is the process of manipulating atoms and molecules on a microscopic scale. According to a UC San Diego ScienceDaily Article, scientists have been using this technique to design vaccine candidates for COVID-19. Nicole Steinmetz, a nanoengineering professor at UC San Diego, has been one such scientist. Instead of relying on older vaccine models, such as live-attenuated or inactivated strains of the virus itself, these “next-generation vaccines” are more stable, easier to manufacture, and easier to administer. 

Since June 1 of 2020, there have been more than one-hundred vaccines in play, with more than a few triumphing through clinical trials. Although many may be years away from deployment, the act of their development will prepare our nations’ leaders for future pandemics. 

There are three forms of these novel vaccines in the mix: peptide-based, nucleic-acid based, and subunit vaccines. All of these are alternatives to classic vaccines, which are slower to produce and sometimes pose the threat of inducing allergic responses.

scientist, microbiologist, virus, molecular biology, laboratory, coronavirus testing, COVID-19Vaccine Development

Peptide-Based Vaccines

Peptides are short chains made up of amino acid monomers. Simple and easily manufactured, peptide-based vaccines are typically made from VPLs, or virus-like particles, which come from bacteriophages or plant viruses. They are composed of peptide antigens, and mimic the patterns of pathogens, making those patterns visible to the immune system. However, they do not produce a strong enough immune response on their own, and thus must be accompanied by adjuvants.

Nucleic-acid Based Vaccines

In the midst of a fast-spreading pandemic, the world needs a vaccine that can be both developed and deployed rapidly. DNA and mRNA vaccines have this potential. DNA vaccines contain small, circular pieces of bacterial plasmids that are engineered to target the nucleus and produce parts of the virus’s proteins. They have a lot of stability, however, they also pose the risk of messing up a person’s pre-existing DNA, leading to mutations. In contrast, mRNA-based vaccines release mRNA into the cytoplasm, which the host cell then translates into a full-length protein of the virus. Because it is non-integrating, it does not have the same mutation risks as DNA-based vaccines.  

Subunit Vaccines 

Subunit vaccines have minimal structural parts of the pathogenic virus, meaning either the virus’s proteins or VLPs. These vaccines do not have genetic material, and instead, mimic the topical features of the virus to induce an immune response. 

The Power of Masks

Delivery Development

One of the most important aspects of a vaccine is accessibility and deployment. In the past, when dealing with live or inactivated vaccines, the lack of healthcare workers to administer the vaccines emerged as a significant concern. Yet, through nanotechnology, researchers have developed devices and platforms to ease these previous issues. They have created single-dose, slow-release implants and patches that can be self-administered, removing pressure from health care workers. Open reporting and the mass culmination of data has allowed for this rapid development of vaccine technologies. Because of these revolutionary advancements, some researchers optimistically predict that COVID-19 has the potential to become merely another seasonal flu-like disease over time.

What Lies Ahead

In these bleak times, it is promising to look at such amazing scientific developments. While a good portion of the general public feels skepticism towards the speed at which these COVID-19 vaccines are being produced, and thus claim they will not take it, I believe that the work of these scientists will not go to waste. As a nation, and as a global community, we will get past it, and come out stronger than ever on the other side. 

Now, ask yourself, would you take a COVID-19 vaccine? 

Shocking Connection Between Ancient Neanderthals and COVID-19

As stated in an article that details the shocking discoveries of an investigation led by Professors Svante Pääbo and Hugo Zeberg, genetic material from our neanderthal ancestors can be linked to the development of severe COVID-19. COVID-19, as I am sure you are all aware, is the disease ravaging the world and is caused by the newly

discovered coronavirus. While most people only have mild reactions to the disease and recover relatively easily, some people with underlying conditions may have a severe reaction to the disease and require hospitalization. However, this new study indicates that certain people may be genetically predisposed to a severe COVID-19 reaction, and it all links back to our 60,000-year-old Neanderthal ancestors.

The study that discovered this connection analyzed the genetic material of 3,000 patients who had both severe and mild COVID-19. The study identified a section of the chromosome that contained the genetic material responsible for the severe COVID-19. Chromosomes are tiny structures located in the nucleus of cells and these structures hold the genetic material that determines virtually everything about the cell. This genetic material is made up of nucleic acids that — when combined into a double-strand helix by covalent bonds between the phosphate, sugar, and base groups– create DNA. The order of the bases in the chain determines the amino acid sequence. We inherit our genetic material from our parents, and chromosomes are present in pairs, with one part of the pair inherited from each parent. This means that you hold genetic information from your earliest ancestors, which could potentially include Neanderthals. Neanderthals were archaic humanoids that were eventually assimilated into the homo sapien species.  However, cross-breeding was required to absorb the Neanderthals into our species, which means that most of the people alive today have a percentage of Neanderthal DNA. If a person holds one of the thirteen variants that are present in Neanderthal DNA, they are far more likely to have severe COVID-19.

Professors Pääbo and Zeberg proved this to be true by discovering that the Neanderthal variants distinctly matched the variants associated with severe COVID-19. However, they discovered that the genetic material only originated from Neanderthals located in southern Europe. Therefore, they concluded that when the Neanderthals of southern Europe merged with present-day people 60,000 years ago, they introduced the DNA region responsible for severe cases of COVID-19. Additionally, the people who possess these Neanderthal variants today are three times more likely to have severe COVID-19. The fact that I found the most interesting is how dramatically the presence of the variants vary in different parts of the world. For example, in South Asia, 50% of the population holds the variants, but in East Asia, almost nobody has them. I also think that it is rather tragic how genetic material that has not had any effect on the world for 60,000 years is just now becoming active. What do you think about this discovery? Why do you believe Neanderthal DNA is causing these extreme cases?

 

A Sweet Post About Sourdough!

When Covid-19 hit the US, some of the biggest quarantine coping mechanisms all revolved around a fan favorite carbohydrate: bread. With the copious amount of time on people’s hands, baking sourdough bread was the perfect activity.

Unlike any other bread, it’s hard to get the perfect tasting sourdough. Research has found that there are biological reasons behind sourdough bread and its taste, but before doing so, it’s important to learn what sourdough bread is made up of, and how it’s made. To help learn more about the process of making sourdough bread from scratch, I got a mini crash course from Little Spoon Farm. The starter (initial mixture) contains flour and water and sometimes salt, which will eventually grow into a diverse selection of microbes (these are tiny living organisms, which in this case are bacteria). The starter has to sit for 7-14 days, and within that time, the starter grows through the flour by eating the sugars within itself. With that growth comes bacteria/microbes and lactic acid, which eventually will allow the bread to be able to leaven in the oven.

Recent studies have shown that each starter is made up of different microbes. One study had 18 professional bakers from all around the globe make their sourdough, and send it to a lab in Belgium, where DNA sequencing was used to identify the microbes in the different starters. Although there were common yeasts and acids found like Saccharomyces cerevisiae and Lactobacillus, the strands and amount of each differed according to the starter. Another study done by Elizabeth Landis, at Tufts University, looked at 560 different starters submitted from all around the world. Through doing so, she found recurring microbe groups within these different sequences. There is still no definitive reason behind the microbe groupings, and why exactly they differ for each starter, but Landis mentioned that certain yeasts “specialize in feeding on distinct sugars,” due to the fact that they are made of different sugar mixtures. Some yeast also lack certain enzymes, which as we learned in class, help break down molecules. In this specific situation, the enzymes within different yeasts feed on and break down sugars. Differing yeasts could also be a reason why sourdough bread has different flavors. (Keep in mind that Landis’ findings are still under review, so there are still limited details on this experiment and not definitive reasoning).

Microbial ecologist, Erin McKenny, further elaborates on how “each microbial community can produce its own unique flavor profile.” For example, when more acetic acid is present in the starter, the bread will have a more sharp and vinegary taste. When the starter produces more lactic acid, it has a more sour and yogurt like taste. Metabolic byproducts within the starter could also potentially add to the complexity of the sourdoughs’ taste. In addition to each microbial community, scientists have identified other features that influence the taste of the bread like temperature. When lactic acid ferments in a warmer area, the bread has a more sour taste, and when it ferments in a colder area, the bread has a more fruity taste.

After looking at multiple articles showing how bakers get their sourdough to have a certain taste, I have learned how important the specifics are when it comes down to making sourdough. One article that gave tips on how to manipulate the taste of sourdough reinforces everything that the main article helped explain, and talks about the importance of keeping a warmer, dry climate to ensure that the bread tastes sour. It turns out that a quarantine treat may be a bit more complex than it appears. It’s interesting to see how biology plays a key role in one of the most prominent foods, and next time you consider making sourdough or get a bread basket from the Cheesecake Factory, you’ll now know the biology behind it.

Some People Can’t Smell Stinky Fish?!

A New York Times article has just reported a new “mutant superpower.” In Iceland, a brand new genetic trait was discovered, in which 2% of the population can’t smell the stinky odor of fish. 

A study of 11,326 Icelanders was conducted, in which each participant was given six “Sniffin’ Sticks (pens imbued with synthetic odors)” of cinnamon, peppermint, banana, licorice, lemon, and fish. The participants were then asked to identify the odors based on how strong each smell was and how good each Sniffin’ Stick smelled. Across the majority, the fish was rated the lowest in pleasantness. However, a small group of people actually enjoyed the scent, noting that it smelled like caramel or even a rose. 

This small group of participants was discovered to have a genetic mutation that enables the TAAR5 gene to form. TAAR5 (Trace Amine Associated Receptor 5) aids in making proteins that recognize trimethylamine (TMA), a chemical found in rotten and fermented fish, and some bodily fluids, including sweat and urine.  TAAR5 is also a G Protein, meaning that it binds guanine nucleotides. And, like other coding proteins, TAAR5 is a quaternary structured protein that has three subunits. Because this protein is incapable of binding guanine nucleotides, it means that there will be at least one “broken” copy of the gene that codes for the inability to smell fish. 

To simplify: TAAR5 recognizes the chemical of smell in fish (TMA), however, with the mutation that prevents the TAAR5 from forming, the smell of fish (TMA) is unrecognizable.

Interestingly, research has shown that this mutation may be a reaction to the customs of Iceland and a possible next step in the evolution of the region. In Iceland, fish takes a prominent place on most menus including dishes like “rotten shark.” These cultural and possibly smelly dishes may explain why this mutation is much more prominent in Iceland compared to Sweden, Southern Europe, and Africa (where the study was repeated). Bettina Malnic, an olfaction expert at the University of Sao Paulo in Brazil, commented on the luck of the region study took place, saying, “if they hadn’t looked at this population, they might not have found the variant [of TAAR5].”

I am VERY sensitive to smell and, at the same time, a lover of sushi, so it definitely fascinates me that there are people out there who don’t have to deal with the odor of smelly fish. This mutation is definitely one I wish I obtained. What do you think about this? Do you think you could have this mutation?!

 

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

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.

 

 

The Problems with Ancestry Tests (23andMe, Ancestry.com, etc.)

Over the past five years or so, ancestry and DNA tests have risen in popularity due to people’s desire to find out what medical conditions they are at risk for, or where their ancestors are from.  The most common concern I have heard about as a result of these tests was that the companies would sell your DNA to third parties or the government (while there is a chance this could be true this will not be the focus of this article).  However, the true problems are not conspiracy driven, yet they are scientifically driven and verifiably true.

Many people using these tests do not realize how these tests actually work and the wrong information they present at times.  The first issue resides in the health screenings of these ancestry tests.  They claim to use your ancestry to see if you are at risk for Alzheimers, certain types of cancer, Parkinson’s, or what type of body type you have.  These companies are not completely lying, however the tests can omit certain things and it is no substitute for going to an actual doctor.

Everything they search for is compared to a reference population, therefore your genes are merely compared to other people who are considered healthy or unhealthy.  These tests do not have access to medical history in order to look for other clinical factors that could accelerate or further exacerbate this potential condition, thus explaining why it is irresponsible to tell people they are at risk for a debilitating disease because someone with similar genetics reported developing a disease that could have resulted from his or her specific lifestyle.

The issue with self-reporting in ancestry tests also can be seen in testing for heritage.  The data these companies use are based off of reference populations (many of which are self-reported especially in the early years of the tests), therefore the same person can receive different results at different times.  The database is constantly changing (which isn’t necessarily only a bad thing) so if the same person takes the test three times in three different years, they are likely to get different results.  If the company recently expands to selling DNA kits in a new area of the world, a person with mixed heritage from the United States can receive different results because the test population of a certain region was extremely small and unspecific before, whereas now they have more of a test population that can change “how Vietnamese you are” (or whatever region that applies to you).

Have you ever known someone who took the DNA test and found out they were not as Greek or Russian (insert anything) as they thought they were? These results are problematic on so many levels when breaking down ancestry.  The first example is that when comparing extremely similar populations, your heritage might not reflect your ancestry that the test finds.  For example: modern English, Scottish, and Irish people have vastly similar results in these tests because they are very similar genetically and geographically, therefore a person can find out they are 50/50 Irish and English, however all of their known relatives can be traced back to 1870s Ireland.  The person is not “less Irish than they thought”; it merely means that centuries of migration and conquering in the region of the British Isles could blend the gene pools even if this person’s family tree of the last two-hundred years can be traced back to one specific town.

Something else important to consider is that ancestry and heritage are not nearly synonymous terms.  Furthermore, two twins could receive different genes from the same parents which could lead to slight changes in genetic makeup.  Your sibling is not “more Swedish than you” in terms of heritage and the culture you were raised in.  The sibling might receive a certain gene from your parents that you did not.

While there are a myriad of problems and hypotheticals to bring up, I will leave you with one last problem. Groups of people that live in diaspora such as Jews, Romani, and Armenians could have problems with these tests.  Ashkenazi Jews from Eastern Europe live in diaspora and have been a migratory group for centuries, leading them to mix in with various gene pools that they settle in.  When an Ashkenazi Jew or Romani (who similarly lived a migratory history) takes an ancestry test, they could feel completely related to their Ashkenazi or Romani heritage, however the intermixing of people over centuries (because they settled in so many places) could come up in the test even though they feel like they have no relationship to the heritage at all.  Romani people also are difficult to pinpoint to one specific region of origin which demonstrates another potential problem with the tests.

While these tests can be a fun activity to do with your friends, make sure you take the results with a grain of salt because you are not necessarily  “less French than you thought”.

 

How Ionizing Radiation Damages Genetic Material and Causes Cancer

 

All around us there is ionizing radiation. It comes from the sun as Ultraviolet rays, in medical equipment as X-rays or Gamma rays, or even from lightning bolts. But what is Ionizing radiation and why is it considered so dangerous. Ionizing radiation is a form of high energy that removes electrons from materials that it comes into contact with. When ionizing radiation comes into contact with cells, it damages them by either directly breaking the bonds between DNA or by ionizing water. Ionized water creates free radicals that then move around and damage DNA. The damage DNA then leads to cancer, but it has never been discovered what types of cancer ionizing radiation causes. However the Wellcome Trust Sanger Institute has finally been able to identify two types of DNA damage caused by ionizing radiation. From previous studies, it has been revealed that radiation damage on DNA leaves a specific fingerprint. By mapping the DNA damage found in cancer cells that were caused by radiation and comparing them to regular cancer cells, the scientists found two mutational patterns that were common in all forms of radiation induced cancers. The first pattern is a deletion of small DNA bases. The second pattern is called balanced inversions, which is where a middle piece of DNA is cut out and attached back to the end. Balanced inversions are not found naturally and can only be caused by radiation damage. From this discovery, scientists hope to be able to identify radiation caused tumors against regular tumors. This may help in finding a specific and more effective cure for the different kinds.

Does Exposure to Toxins In the Environment Affect One’s Offspring’s Immune System?

A study has recently surfaced stating that maternal exposure to industrial pollution may harm the immune system of one’s offspring and that this impairment is then passed from generation to generation, resulting in weak body defenses against viruses.

Paige Lawrence, Ph.D., with the University of Rochester Medical Center’s Department of Environmental Medicine, led the study and conducted research in mice, which have similar immune system functions as humans. Previously, studies have shown that exposure to toxins in the environment can have effects on the respiratory, reproductive, and nervous system function among generations; however, Lawrence’s research is the first study to declare that the immune system is also impacted.

“The old adage ‘you are what you eat’ is a touchstone for many aspects of human health,” said Lawrence. “But in terms of the body’s ability to fights off infections, this study suggests that, to a certain extent, you may also be what your great-grandmother ate.”

“When you are infected or receive a flu vaccine, the immune system ramps up production of specific kinds of white blood cells in response,” said Lawrence. “The larger the response, the larger the army of white blood cells, enhancing the ability of the body to successfully fight off an infection. Having a smaller size army — which we see across multiple generations of mice in this study — means that you’re at risk for not fighting the infection as effectively.”

In the study, researchers exposed pregnant mice to environmentally relevant levels of a chemical called dioxin, which is a common by-product of industrial production and wast incineration, and is also found in some consumer products. These chemicals eventually are consumed by humans as a result of them getting into the food system, mainly found in animal-based food products.

The scientists found the production and function of the mice’s white blood cells was impaired after being infected with the influenza A virus. Researchers observed the immune response in the offspring of the mice whose mothers were exposed to dioxin. Additionally, the immune response was also found in the following generations, as fas as the great-grandchildren (or great- grandmice). It was also found that this immune response was greater in female mice.  This discovery now allows researchers to have more information and evidence to be able to more accurately create a claim about this theory.

As a result of the study, researchers were able to state that the exposure to dioxin alters the transcription of genetic instructions. According to the researchers, the environmental exposure to pollutants does not trigger a genetic mutation. Instead, ones cellular machinery is changed and the immune response is passed down generation to generation. This discovery explains information that was originally unexplainable. It is obviously difficult to just avoid how much toxins you are exposed to in the environment, but it is definitely interesting to see the extent of the immune responses in subsequent generations. We can only hope that this new information, and further discoveries, help people adjust what they release into this world that results in these harmful toxins humans are exposed to, and their offsprings.

 

 

 

Stem Cells and CRISPR

Many cells can reproduce but there are a few types of cells that are not able to reproduce. One of these types are nerve cells, the cells that cary messages from your brain to your body.  There are many ways nerve cells can be destroyed or damaged, by trauma or drug use.  Millions of people are effected by losing nerve cells and for so long no one could think of a way to recreate them; until the discovery of stem cells.

After fertilization, and when the newly formed zygote is growing, it is made up of a sack of cells.  Some of these cells are stem cells which develop according to their environment. Because of the behavior of stem cells, scientists theorized that if they placed stem cells in the brain or spinal chord, two areas that have an abundance of neurons, the stem cells would turn into a neuron because of the environment it was in.  But, when they tried introducing stem cells into the body, the immune system treated them as an foreign body, as it should. Our immune system has to treat anything that does not come from our body as an enemy or we could get extremely sick.  However, the downside is organ transplants, blood transfusions, etc. are dangerous because they could cause a serious immune rejection.

Someone experiencing a spleen transplant rejection

Cells have a surface protein that displays molecular signals to identify if it is self or foreign.  Removing the protein causes NK (natural killer) cells to target the cell as foreign. Scientist haven’t been able to figure out how to make a foreign cell not seem foreign until Lewis Lanier, chair of UCSF’s Department of Microbiology and Immunology, and his team found a surface protein that, when added to the cell, did not cause any immune response.  The idea would be to use CRISPR/cas9 to edit the DNA of the stem cells, and in doing so would remove the code for the current surface protein and add the code for the new surface protein.

After the scientists had edited the stem cells, to have the correct signal protein, they released them into a mouse and observed that there was no immune rejection. Truly amazing. Maybe brain damage could be helped by this science one day. Tell me your thoughts on Stem Cells in the comments!

For more information, please go check out the primary source of this article.

 

 

New anti-CRISPR Proteins Serving as Impediments to this Miraculous System.

CRISPR-Cas9 systems are bacterial immune systems that specifically target genomic sequences that in turn can enable the bacterium to fight off infecting phages. CRISPR stands for “clusters of regularly interspaced short palindromic repeats” and was  first demonstrated experimentally by Rodolphe Barrangou and a team of researchers at Danisco. Cas9 is a protein enzyme that is capable of cutting strands of DNA, associated with the specialized stretches of CRISPR DNA.

Diagram of the CRISPR prokaryotic antiviral defense mechanism.

Recently, a blockage to the systems was found by researchers which are essentially anti-CRISPR proteins. Before, research on these proteins had only showed that they can be used to reduce errors in certain genome editing. But now, according to Ruben Vazquez Uribe, Postdoc at the Novo Nordisk Foundation Center for Biosustainability (DTU), “We used a different approach that focused on anti-CRISPR functional activity rather than DNA sequence similarity. This approach enabled us to find anti-CRISPRs in bacteria that can’t necessarily be cultured or infected with phages. And the results are really exciting.” These genes were able to be discovered by DNA from four human faecal samples, two soil samples, one cow faecal sample and one pig faecal sample into a bacterial sample. In doing so, cells with anti-CRISPR genes would become resistant to an antibiotic while those without it would simply die. Further studies found 11 DNA fragments that stood against Cas9 and through this, researchers were ultimately able to identify 4 new anti-CRIPRS that “are present in bacteria found in multiple environments, for instance in bacteria living in insects’ gut, seawater and food,”  with each having different traits and properties.  “Today, most researchers using CRISPR-Cas9 have difficulties controlling the system and off-target activity. Therefore, anti-CRISPR systems are very important, because you want to be able to turn your system on and off to test the activity. Therefore, these new proteins could become very useful,” says Morten Sommer, Scientific Director and Professor at the Novo Nordisk Foundation Center for Biosustainability (DTU). Only time will tell what new, cool, and exciting discoveries will be made concerning this groundbreaking system! What else have you guys heard? Comment below!

CRISPR used to Control Genetic Inheritance in Mice!

Scientists around the world have been using CRISPR/Cas9 in a variety of plant and animal species to edit genetic information. Although this has been tested recently on insects, it is currently moving towards testing mammals. It happens to be more difficult with mammals due to the longevity between generations. However, It’s been done!!

UC San Diego researchers have developed a new active genetic technology in mice. Graduate student Hannah Grunwald, Assistant Researcher Valentino Gantz and colleagues led by Assistant Professor Kimberly Cooper, layed the groundwork for further advances based on this technology, including biomedical research on human disease.Image result for mice

“To demonstrate feasibility in mice, the researchers engineered an active genetic “CopyCat” DNA element into the Tyrosinase gene that controls fur color. When the CopyCat element disrupts both copies of the gene in a mouse, fur that would have been black is instead white, an obvious readout of the success of their approach. The CopyCat element also was designed so that it cannot spread through a population on its own, in contrast with CRISPR/Cas9 “gene drive” systems in insects that were built on a similar underlying molecular mechanism.”

The project duration was two years, and the researchers used many ways to “determine that the CopyCat element could be copied from one chromosome to the other to repair a break in the DNA targeted by CRISPR”. Some gene that was originally existent on only one of the two chromosomes was copied to the other chromosome. They were able to convert one genotype from heterozygous to homozygous, and they were able to tell in that there were  as many as 86 percent of offspring that inherited the CopyCat element from the female parent instead of the usual 50 percent.

The test was successful for the female mice’s production of eggs, but not for the males production of sperm. The researchers predict this is a possibility to a difference in the timing of male and female meiosis.

As this test was only the beginning, researchers such as those at UC San Diego hope to soon move on to research on human disease. They say that “Future animal models may be possible of complex human genetic diseases, like arthritis and cancer, which are not currently possible.”, and with their hard work, their research can lead to miracles.

Planet of the (CRISPR-Edited, Cloned) Apes

Several months ago, scientists in China cloned five gene-edited macaque monkeys. The clones were made through the somatic cell nuclear transfer method (SCNT)—a process in which a viable embryo is created from a body cell and an egg cell—that was used to produce the first primate clones around a year ago. In this instance, however, the monkeys’ genomes were first edited using CRISPR-Cas9—a unique genome editing tool that enables geneticists to edit parts of the genome by removing, adding, or altering sections of the DNA sequence—to show symptoms of sleep disorders by eliminating BMAL1, one of the positive elements in the mammalian auto-regulatory TTFL, which is responsible for generating molecular circadian rhythms. The result? The monkeys exhibited a wide range of circadian disorder phenotypes, including elevated night-time locomotive activities, reduced sleep time, reduced circadian cycling of blood hormones, increased anxiety and depression, and other schizophrenia-like behaviors. 

File:Macaque Monkey (16787053847).jpg

Macaque Monkey

Naturally, the results of the investigation triggered much backlash. According to Carolyn Neuhaus of The Hastings Center, the researchers viewed the suffering of the monkeys as a triumph, and failed to consider the moral implications of their investigation. “It’s very clear that these monkeys are seen as tools,” she told Gizmodo, the latter publication writing in a similar sentiment, “Their experiment is a minefield of ethical quandaries—and makes you wonder whether the potential benefits to science are enough to warrant all of the harm to these monkeys”. 

Nevertheless, the researchers involved in the experiment remain firm in their support of the experiment—the goal of which was to produce genetically identical monkey models of disease for biomedical research—on both moral and scientific grounds. “We believe that this approach of cloning gene-edited monkeys could be used to generate a variety of monkey models for gene-based diseases, including many brain diseases, as well as immune and metabolic disorders and cancer,” stated Qiang Sun, one of the research paper’s authors and director of the Nonhuman Primate Research Facility at the Chinese Academy of Science’s Institute of Neuroscience in Shanghai. Moreover, Reuters reported, “Xinhua [the state news agency] said the program, supervised by the institute’s ethics panel, was in line with international ethical standards for animal research”. Time will tell, ultimately, if the results of their experiment prove consequential on a larger scale. 

Scientist from China creates a baby resistant to HIV

The development of CRISPR technology has drastically progressed in the recent years, and He Jiankui, a scientist from China, took a step that most people judge to be crazy: he used CRISPR technology to create a human who is resistant to the HIV virus.

What is CRISPR? Good question.

CRISPR-Cas9 is a gene editing tool made from an ancient bacterial immune system. In bacteria, this system identifies DNA of invading viruses and send in different enzymes, such as Cas-9 to target and cut out a piece of DNA. Researchers quickly realized that almost any sequence of DNA can be cut out and modified the system to any sequence desired, even one that can prevent HIV. This is what Jianku’s work comprised of.

Jiankui and his team targeted the gene CCR5, a gene that provides the blueprint for the cell surface protein involved in the immune system, in the DNA of human embryos. The cell surface protein is usually involved in relaying information between cells, and HIV can use it to dock onto cells, infecting them with their own genetic material. Jianku eliminated the CCR5 gene to prevent HIV from docking onto any of the baby’s cells. However CRISPR-Cas9 induces mutations that scientist cannot fully control, and Jianku could not replicate the gene to the exact level. So, he instead created a “mixture of disrupted gene products”, which could potentially have a negative effect on human health.

At first glance, Jiankui’s experiment might be seen as beneficial, but Jiankui’s decision to create this human has been considered by other scientist as premature, drastic, and unethical, and has caused a lot of controversy. Although this was not the first time a scientist tampered with a human embryo, many scientists are outraged and believe that his experiment was a violation of human ethics. According to an article written by Allison Eck, the most notable ethical breach was conducting this experiment without the consent of other scientists, ethicists, regulators, or institutional review boards.

Debates over Jianku’s work have been circulating since the announcement of his experiment. Personally, I think that in the future, if we can prevent HIV and other harmful diseases that cause death, CRISPR can be an effective tool. However, as of now, we do not fully understand are aware of all of its effects. Therefore it is dangerous to test it on other humans. In the wrong hands, this powerful technology might be used in the wrong way and can cause huge repercussions. What do you think?

 

The Collateral Damage of CRISPR-Cas9

 

CRISPR’s ‘precise’ gene-editing has actually been damaging other parts of the DNA sequence, according to a recent study. Photo from this source.

Of the various gene-editing techniques, CRISPR-Cas9 is the fastest, simplest, and most accurate gene-altering method known to date. Comprised of simply two parts, CRISPR-Cas9 snips through targeted segments of DNA and causes a change in the genetic code. Scientists are hopeful that we can soon use this method to cut out mutations that code for HIV, cancer, and sickle cell disease. However, a study published in Nature Biotechnology has revealed an unwanted side-effect of CRISPR.

When using CRISPR-Cas9, there are two major molecules that create a mutation, or change, in a DNA segment. The first is an enzyme called Cas9. This enzyme works like a pair of scissors and that cuts the two helices at a specific location so DNA can be altered. The second tool used in this process is the guide RNA (gRNA) that binds to the DNA and ensures that the Cas9 molecule cuts the DNA in the correct place. Finally, after the incision, the DNA will seal itself back together, without a trace of the deleted segment.

Such a precise process seems flawless. In theory, one should be able to cut out the unwanted genetic material and our DNA should perfectly repair itself. Unfortunately, senior group leader and director of the study at Wellcome Sanger Institute in England, Allan Bradley, stated that “CRISPR is not as safe as we thought.” Through a systematic and tedious approach, Bradley and his colleagues edited a series of mouse and human cells with CRISPR and then examined DNA base pairs father and farther away from the cut site. By examining millions of base pairs, the team landed upon unsettling news.

Bradley and his team found that huge chunks of DNA were inadvertently deleted, mutated, and rearranged millions of base pairs away from the cut site. The DNA was mutated so immensely that cells lost function in 15% of cases. Because these CRISPR-induced mutations were shown so far away from the cut site, this information could have easily been overlooked in other studies.  

This research poses questions on the accuracy of such gene-editing methods. What are the long-term effects of genetic engineering with CRISPR? How can we ensure that base pairs so far away from the cut site aren’t altered? Although this is somewhat discouraging news for the CRISPR community, this newfound information is motivating more researchers to improve CRISPR technology before making it widely accessible.

Read the full article here.

The Cure Before Being Born

lab mouse – Photo credit to Wikimedia Commons

A team of researchers from the University of Pennsylvania and Children’s hospital of Philadelphia has seen exciting results in their experiment on mice fetuses with an inherited liver disease.  The team removed the amniotic sac containing the fetus from the mother’s uterus, before injecting in a vein of thee fetus near the liver with CRISPR. This was to ensure that the genetic modification would be in the liver cells and would not affect any other vital organs. The fetus was then placed back into the uterus and the mother was thankfully unaffected by the modification, allowing for all the babies to be born without any issues.

The team used a more recently invented form of CRISPR called base editing instead of the well-known  CRISPR-CAS9.  Rather than cutting and inserting a sequence of DNA, a single nitrogenous base was replaced with another.  This newer method showed significantly less “genetic havoc”, unknown consequences for a cell that has been genetically modified with CRISPR.

The disease they targeted was a tyrosinemia type I, a mutation that effects 1 in 100,000 newborns globally, which causes causes the amino acid tyrosine to be metabolized into toxic products, which build up and cause damage to liver, and can eventually destroy it.   The scientist sought to disable the HPD gene, which creates enzymes that help to break down tyrosine.  By changing a cytosine base to thymine base, the toxic products are never produced.

Tyrosinemia type I – Photo credit to Wikimedia Commons

As the mice grew and developed, the researchers were astounded to find that despite only 15% of their liver cells having been the altered with the base edit, the genetically modified mice were surviving better and gaining more weight compared to those treated with traditional methods of drugs and monitored diet.

This is definitely a step in the right direction to eliminating genetic diseases, but base editing, especially for diseases due to multiple mutations might be more difficult, as many bases would need to be edited.  What do you think: more safe, yet possibly difficult base editing method or cut-insert method?

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