BioQuakes

AP Biology class blog for discussing current research in Biology

The journey to find a cure for cancer

What exactly does ‘epigenetic’ mean? Well epigenetic literally means “in addition to changes in genetic sequence.” The term now means any procedure to change genetic activity without changing the sequence of the actual DNA. So why is this important? Epigenetics can affect a lot of scientific research. For example DNA methylation is a hugely important epigenetic modification.

DNA methylation is where a methyl group would be added to a cytosine in a DNA sequence changing its function. This can be used in embryonic development, X-chromosome inactivation, genomic imprinting, gene suppression, carcinogenesis and chromosome stability. This means DNA methylation is very vital to growth and development- as it is a natural process- however can affect bad cells.

Examples of this are with cancer cells. DNA Methylation patterns- adding a group- are interrupted and changed when cancer is present. DNA methylation done on the promoters in tumor cells can turn off the expression of genes. In humans this can cause disruption of vital developmental pathways. This was then tested in an experiment (for now we will only observe human results because it was tested on mice as well) They tested human normal brain tissue vs. cancerous.

After testing the DNA methylation patterns on tumors, they found that 121 loci (loci is the central “hot spot” of genes) had strong methylation compared to the normal brain tissue which had 60% less. So what does all this mean??

Basically DNA methylation is a good thing in a normal environment. When cancer is present DNA methylation can change and be harmful in a negative environment such as a tumor because it causes hypermethylation.

While the take away is essentially the obvious- cancer is bad- scientists can use this data to find a correct cure for cancer and to create better medicine as some can harm even more by increasing DNA methylation in tumors. For more information on this click here.

 

 

 

What is CRISPR-Cas9?

CRISPR-Cas9 is a new(ish) technology that is used for knocking out human genes in cell lines for the purpose of seeing what these genes do. CRISPR-Cas9 has a “protein scissor”, the cas-9 protein, and a location that shows the cas9 where to bind to. The “location” is actually a strand of RNA that is complementary to a specific strand of DNA. This RNA strand is like glue in that it binds to the DNA and allows the Cas9 to cut the DNA. This process or the CRISPR-Cas9 technology is like an endless cycle of cutting and repairing DNA until the repair enzyme can no longer repair the DNA or makes a mistake. This technology can make the process of cutting and disabling genes five times faster. It allows scientists to edit parts of a genome by altering, removing, or adding certain sections of DNA. While this technology can be very useful in trying to understand what genes do it does have a downside, “these approaches are costly and time-consuming to engineer, limiting their widespread use, particularly for large scale, high-throughput studies.” The picture below shows what this process looks like on a very basic scale. Hopefully this technology will eventually allow us to fully understand what every gene does.

 

Blame your Parents for your Stress?

Epigenetics is the study of inheritable changes in gene expression not directly coded in our DNA. Scientists at Tel Aviv University have shown that stress, induced by traumatic events, can be passed on to offspring. The study refers to this stress as passing on “memories.” The study finds the exact way that the inheritance of environmental influences is turned “on” and “off.” RNA sequences that regulate gene expression are partially responsible for deciding when the inheritance is on or off.

Scientists found that C.elegans worms only passed on inheritable epigenetic responses for a few generations (using small RNAs that target green fluorescent protein). This led them to believe that epigenetic responses die out eventually. However, this did not account for the possibility that inheritance could be regulated.  Scientists discovered that in order to create new small RNAs that allow a response to be passed on to multiple generations, they needed RdRP enzymes. These amplify heritable RNAs for generations. Certain genes that they called “MOTEK” (Modified Transgenerational Epigenetic Kinetics) were involved in turning on and off epigenetic transmissions. They switched on and off the small RNAs that the worms use to regulate genes using a feedback interaction between gene-regulating small RNAs and MOTEK. This determines whether an epigenetic memory will be passed on, and for how many generations.

Even though this study was done on worms, these scientists have said that these basics can possibly lead to discovery of inheritance for all organisms. This small bit of research can lead to endless amounts of knowledge for similar mechanisms in humans.

Overview of Epigenetics:

https://commons.wikimedia.org/wiki/File:Epigenetic_mechanisms.jpg

Link to Original Page     Link to Licensing

https://www.flickr.com/photos/usdagov/30884756422

If You Want the Bull, Take its Horns

Everyone loves milk. It’s the foundation of Ice Cream, it’s an essential component in any good bowl of cereal, it’s the foundational ingredient in the creamy center that unites the Oreo, and pro tip: you can put chocolate syrup in it (I thought of that; I call it “ChocoLeche” I think it could really catch on).

 

Before I continue, I’d like to take a moment of silence for those cursed by the demon known commonly as lactose intolerance. Your lives are a miserable nightmare that I don’t even want to think about. #findacure .

 

Like I said everyone loves milk, and everyone knows it comes from cows. Few people however are aware of the fact that the cow that produces milk is different than the cow that produces the much beloved meat products such as steak and hamburgers. The Cows that are used for meat are of the Angus variety. The Cows for dairy products are Holstein Cows. One major difference that used to exist between the two is that Holstein, or dairy cows, had horns, unlike the meatier Angus cows which did not have horns. Thanks to Crispr-Cas9, scientists from UC Davis lead by Dr. Alison Van Eenennaam have rid Holstein cows of their horns, and in doing so have granted dairy cows everywhere with a higher quality of life.

https://www.flickr.com/photos/usdagov/30884756422

Source

Photo by

U.S. Department of Agriculture

The first question that needs to be answered is why would this be important. Why does it matter that we got the horns off of Holsteins? It’s important first because these horns put cows at risk from each other. Cows with horns might advertently or inadvertently use them to injure themselves, other cows or their handlers. Many previously solved this problem by dehorning the cows, which involves burning the horns off and is extremely painful for the cows. Without horns to begin with no cows need to be dehorned and fewer cows are injured. As Dr. Jeff Burkhardt puts it “From the animal welfare perspective, Dr. Alison Van Eenennaam’s research is worthy of high praise: The prospect of reducing the pain associated with de-horning, which itself was introduced to eliminate risks of animals hurting themselves and others, is exactly the kind of thing that animal scientists should be doing” – Jeff Burkhardt. The Ethics of Gene editing in general is a complex and hotly debated issue right now due to the novelty of the CRISPR system, however, in this instance I feel as though the researchers are on very sound moral ground. They have made a change that safely and indisputably decreases the pain a dairy cow experiences. If you disagree I’d invite you to burn two holes in the side of your head, and reconsider whether you’re comfortable bestowing that treatment on another living creature.

The second question is how did they do this. The answer is deceptively simple. As I formerly noted, Angus cows do not possess horns. What they do possess is a gene that prevents the growth of a horn. The group of researchers at UC Davis first identified this gene and its cause. They then used CRISPR-Cas9 to cut it out of an Angus Cow’s DNA and inserted it into the DNA of a Holstein cow. The Angus cow gene prevents horn growth in Holstein cows, and the Holstein cows officially became a GMO, or genetically modified organism. A GMO that no longer has horns.

 

DYING to Know Your Predicted Lifespan? Look No Further!

Have you ever wondered how long you’ll be around for? Well, scientists at the German Cancer Research Center, Saarland Cancer Registry, and the Helmholtz Research Center for Environmental Health have made great strides in predicting human mortality. How so? Through a controlled study in which they analyzed patterns in DNA methylation.

DNA methylation, an epigenetic phenomenon, occurs in the body in order to inhibit the transcription of DNA. Methyl groups attach to specific combinations of DNA building blocks called CpGs. In this experiment, the scientists analyzed the DNA from blood cells taken from 1,900 participants fourteen years prior. As they were all older adults, many of the participants had died within that fourteen years. The scientists analyzed methylation at 500,000 of the CpGs, trying to figure out if there was a correlation to chances of survival. Spoiler alert: at 58 of these CpGs there proved to be a strong correlation between methylation level and mortality.

One interesting discovery was that 22 out of the 58 influential CpGs were identical (in terms of amount of methylation) to the CpGs of smokers that the scientists had analyzed in a previous study. What does this mean? Smoking definitely leaves its mark on your genome. However, the good news is that DNA methylation can be reversed, so if a smoker quits his or her risk of dying could drop significantly.

The second major finding of this study was that only 10 out of the 58 CpGs can actually determine mortality risk. The scientists took the 10 CpGs with the strongest correlation with mortality and created an epigenetic risk profile. This profile can predict “all-cause mortality”. Participants who were overly-methylated at five or more of these spots were seven times more likely to die in the fourteen year span than their properly-methylated counterparts.

This study is a major breakthrough in understanding human mortality, because analyzing DNA methylation is so much more accurate than looking at SNPs. The researchers plan on using their new knowledge to find out how to improve methylation profiles at these CpGs.

Does it surprise you that only 10 spots on the genome can have such a profound effect on duration of life? Do you think there could be an even more accurate predictor of mortality than DNA methylation levels? Let me know in the comments!

Don't Smoke!

Credit: Nina Matthews Photography, URL: https://www.flickr.com/photos/21560098@N06/5642711277

Original Article: https://www.sciencedaily.com/releases/2017/03/170320104008.htm

Epigenetics Fight Against Pancreatic Cancer

Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most deadly forms of of Pancreatic Cancer with a less than 10 percent, 5-year survival rate. Unfortunately, it is the most common form of Pancreatic Cancer.  However, scientist were given hope to increase the survival rate when a protein was identified as a aid to the development of PDAC. The protein is Arginine Methyltransferase 1 (PRMT1) and it is involved in gene transcription, DNA signaling, and DNA repair.

It is said that research done by Giulio Draetta, M.D., PhD “strongly suggest a role for PRMT1 in PDAC development and illuminate a path toward the development of therapies for patients in desperate need of innovative solutions”. Draetta’s  team developed a platform called PILOT, Patient-Based In Vivo Lethality to Optimize Treatment. The PILOT technology allows researchers to systematically identify epigenetic drivers in patient-derived tumors. The research found hat PRMT1 is a epigenetic driver for PDAC. Using CRISPR, the team was able to confirm that when the proteins were removed from DNA, the growth of the cancer cells were significantly impaired. There is hope that this recent development can save many lives and increase the survival rate of Pancreatic Ductal Andeocarcinoma.

https://commons.wikimedia.org/wiki/File:Diagram_showing_stage_T4_cancer_of_the_pancreas_CRUK_267.svg

 

CRISPR/Cas9, Omnipotent Cure or New Toy for the Rich and Famous?

Editing the human genome has been a highly controversial subject matter in the field of bioethics as advancements with techniques like CRISP/Cas9 allow for precise DNA cutting and sequence addition.  As of February 14th, a panel for the National Academies of Sciences and Medicine concluded that altering DNA in gametic cells is ethical as long as it is only utilized to cure genetic diseases that could be passed down to offspring and not to simply enhance health or certain characteristics.  This is novel as former recommendations given by organizers of a global summit on human gene editing proposed that gene manipulation via molecular scissors should not be used in the production of babies.  However, it is important to note that while the Nation Academies reports often impact policy formation in the United States and around the world, they hold no actually legislative weight and authority rests in hands of Congress, regulatory agencies like the FDA, and both state and local governmental bodies.

Depiction of CRISPR/Cas9 protein complex by Thomas Splettstoesser, source

Some scientists like panel cochair Alta Charo of the University of Wisconsin-Madison Law School are still highly skeptical of heritable gene editing and have not yet pinpointed times when it is just to perform.  “We are not trying to greenlight heritable germline editing,” says Charo, “We’re trying to find that limited set of circumstances where its use is justified by a compelling need and its application is limited to that compelling need.  We’re giving it a yellow light.”  Others hold the notion that any manipulation of the germline will inevitably culminate in the creation of “designer babies”.  In their minds, this could stigmatize disabled people, heighten inequality between the rich and those who can’t afford the treatment, and possibly start a new wave of eugenics like seen in the sci-fi film Gattaca (1997). Marcy Darnovsky, executive director of the Center for Genetics and Society in Berkeley, California, comments, “Once you approve any form of human germline modification you really open the door to all forms.”

On the other end of the spectrum, many are thrilled with the decision and see a bright future for the human race.  Sean Tipton, a spokesman for the American Society for Reproductive Medicine in Washington, D.C., states, “It looks like the possibility of eliminating some genetic diseases is now more than a theoretical option.  That’s what this sets up.” Indeed, debilitating diseases caused by mutations in single genes like cystic fibrosis and Huntington’s could become a thing of the past in the near future.  Unfortunately, genome editing to cure more complex diseases and disorders associated with mutations in multiple genes (autism, schizophrenia, etc.) is still very far in the future.

In reality, there is little to worry about in the area of germline editing for now as panelist Jeffrey Kahn of Johns Hopkins University ensures that the beginning of heritable gene alteration is closed off until requirements can be met at the legislative level.  Additionally, the panel presented numerous obstacles that must be cleared before germline manipulation can become a reality.  Nita Farahany, a bioethicist at Duke Law School claims, “Some people could read into the stringency of the requirements to think that the benefits could never outweigh the risks.”  Also, the requirement to follow up with multiple generations of genetically modified children to study what consequences the therapy holds for future offspring is an invasion of privacy.  Farahany adds that, “You can’t bind your children and grandchildren to agree to be tracked by such studies.”  On top of all this, it is extremely difficult to draw distinctions between therapies and enhancements. George Church, a Harvard University geneticist, remarks that nearly all medical advancements could be considered life-enhancing.  “Vaccines are advancements over our ancestors. If you could tell our ancestors they could walk into a smallpox ward and not even worry about it, that would be a superpower.”

So, where will germline editing take the species Homo sapiens?  Is the cure for cancer on the horizon?  Would the pursuit of creating perfect humans be beneficial or harmful for society?

How A Chemical From the Cypress Tree Could Advance Epigenetics Against Cancer

by Czechmate on Wikimedia Commons

Found in the essential oil extracted from the bark of a cypress tree, a chemical named hinokitiol shows potential to impact epigenetic tags on DNA and stop the activity of genes that assist the growth of tumors.

In order to develop an of understanding cancer, researches have had to comprehend the DNA methylation, an epigenetic function which controls gene expression. In regular DNA methylation, genes that work to fight against tumors are turned on, reducing the risk of cancer. However, if DNA methylation is negatively altered, then those cancer-fighting genes will be silenced, helping to progress cancer development. Scientists have tried to combat irregular DNA methylation and over-silencing of genes by creating epigenetic anti-cancer medications that reverse non-beneficial methylation effects. Like in most cases of medication usage, the users face unappealing side effects. Hinokitiol is attractive to scientists because it is a natural compound with many health benefits and way less side effects than modified drugs that can possibly cause mutagenesis and cytotoxicity.

 

Researchers from the Korea University College of Medicine tested the productivity of the hinokitiol chemical in a study by giving doses of it to colon cancer cells. It was found that this chemical helped to inhibit the colon cancer cells efficiency without affecting the colon cells without cancer. The scientists also found through careful inspection that the presence of hinokitiol decreases the expression of proteins DNMT1 and UHRF1; both of which are proteins that encourage carcinogenesis. In summary, the doses of hinokitiol appear to have allowed normal cells to remain healthy, while reducing the ability for the colon cancer cells to thrive and ceasing the production of proteins that promote cancer maturation.

Researchers are continuing their search for natural compounds, as opposed to artificial medications, that can prevent the flourishing of cancer in our bodies through playing a positive role in gene expression and DNA methylation.

http://www.whatisepigenetics.com/cypress-trees-epigenetically-protect-cancer/

 

 

https://commons.wikimedia.org/wiki/File:Raindrops_on_leyland_cypress.jpg

The Miracle of CRISPR/Cas9 in Gene Editing

Some scientists say, “you can do anything with CRISPR” and others are absolutely astonished and amazed.

CRISPR can rapidly change any gene in any animal or plant with ease. It can fix genetic diseases, fight viruses, sterilize mosquitos and prepare organs for transplant. The possibilities are endless – and the prospect of designer babies isn’t far off.

https://en.wikipedia.org/wiki/CRISPR#/media/File:Crispr.png

Dead Cas9 can fix a single base pair typo in DNA’s genetic instructions. It can convert a C-G into a T-A pair. Also, we can attach fluorescent tags to dead Cas9 so researchers can locate and observe DNA or RNA in a living cell. Dead Cas9 can also block RNA Polymerase from turning on a gene, in CRISPRi. In CRISPRa, a protein that turns on genes is fused to dead Cas9.

CRISPR can be used for anything involving cutting DNA. It guides molecular scissors (Cas9 enzyme) to a target section of DNA & works to disable or repair a gene, or insert something new.

Many scientists have been thinking of improvements for this miracle gene editor. RNA Biologist Gene Yeo compares the original Cas9 to a Swiss army knife with only one application – a knife. He says that by bolting other proteins and chemicals to the blade, they transformed the knife into a multifunctional tools.

CRISPR/Cas9 is special because of its precision. It is much easier to manipulate and use compared to other enzymes that cut DNA. By using “guide RNA” it can home in on any place selected by the researcher by chemically pairing with DNA bases.

While Cas9 does have some problems, scientists definitely see the potential for greatness with a few tweaks. They wanted to ensure permanent single base pair changes, and they increased that from 15 to 75 percent. Liu used a hitchhiking enzyme called cytidine deaminase.

Scientists researched chemical tags on DNA called epigenetic marks. When scientists placed the epigenetic marks on some genes, activity shot up. This provided evidence that the mark boosts gene activity.

Case can also revolutionize RNA biology. The homing ability of CRISPR/Cas9 is what makes this seem possible. It was found that Cas9 could latch on to mRNA.

CRISPR/Cas9 was first found in bacteria as a basic immune system for fighting viruses. It zeroes in on and shreds the viral DNA. Half of bacteria have CRISPR immune systems, using enzymes beyond Cas9.

Overall scientists predict that in the next few years, results will be amazing. The many ways of using CRISPR will continue to multiply and we will see where science takes us.

Source: https://www.sciencenews.org/article/crispr-inspires-new-tricks-edit-genes

Other Sources: https://www.neb.com/tools-and-resources/feature-articles/crispr-cas9-and-targeted-genome-editing-a-new-era-in-molecular-biology

Using CRISPR to Prevent Chronic Pain & Inflammation

(https://commons.wikimedia.org/wiki/File:Rheumatoid_Arthritis_Hands.jpg)

Researchers at the University of Utah have recently figured out a way to use CRISPR gene-editing techniques to reduce chronic pain and inflammation.

Normally, inflammation around damaged tissue signals various cells to produce molecules that destroy the damaged tissue. However, this can quickly devolve into chronic pain when the tissue destruction does not stop.

The researchers have found a way to use CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat) to relieve and prevent chronic pain. Unlike most popular CRISPR techniques, theirs does not involve altering the gene sequences– it instead relies upon epigenetics, and modifying the expression of the genes in the cytokine receptors in inflammatory areas, to prevent cells from producing the molecules that destroy tissue.

The treatment is delivered through a virus, which is injected into the inflammatory site. It is more potentially therapeutic than current treatments for chronic pain, in that it actually prevents tissue destruction and future pain, rather than just relieving present pain. The method is approximately ten years away from being used to treat human patients.

Who is the “New Kid on the Block?”

CRISPR/ Cas 9 is newest technology, that is exciting many scientists. CRISPR stands for clustered, regularly interspaced, short, palindromic repeats. This system is a a bacterial defense mechanism thats is RNA based. Its goal is to eliminate and identify DNA which is foreign that would normally invade the bacteriophages and the plasmids. The Cas endonuclease has the role of cleaving at specific locations of the DNA, by being guided by RNA. Now that we have a general idea what this system is lets find out how it can be beneficial!

We understand that CRISPR, at the DNA cleavage site, has the ability to introduce mutations or genetically engineered DNA.

https://commons.wikimedia.org/wiki/File:DNA_Overview2.png

Here are some examples of how CRISPR can be used in the future:

  1. Treat disease in humans
  2. Eliminate Malaria
  3. Give humans other animals’ organs
  4. Create new medications
  5. Genetically modify humans

As the list above only refers to some of the many possibilities CRISPR can have, we can see that this new technology can help humans is many ways. It is evident why CRISPR is referred to as “the new kid on the block.” Hopefully this new system will be able to accomplish the things listed above and many more!

https://www.jax.org/news-and-insights/jax-blog/2014/march/pros-and-cons-of-znfs-talens-and-crispr-cas

Here are some other interesting sites about CRISPR to learn more!

http://www.popularmechanics.com/science/a19067/11-crazy-things-we-can-do-with-crispr-cas9/

http://www.sciencealert.com/this-video-explains-perfectly-why-crispr-really-will-change-humanity-forever

Avenging Lamarck: The Epigenetics of a Fish

The laughingstock of biology classrooms everywhere, the footnote to Charles Darwin and his widely acclaimed theory of natural selection, the scientist who has caused many a biology student to stop and wonder why he or she should even know his name, Jean Baptiste Lamarck has gotten a bad rap among student’s across the country. Predicting that evolution in species resulted from individual species adapting to their environment and morphing their bodies to better survive and reproduce, passing their adapted traits to their offspring, Lamarck has been criticized by students everywhere for simply not being correct. However, he wasn’t entirely wrong. Recent research conducted in the Gulf of St. Lawerence off the Labrador Peninsula has revealed that skate fish  in the area have developed differences in terms of size from other skate fish because individual organisms are able to turn on and off select genes.

https://en.wikipedia.org/wiki/Mottled_skate

The ability to turn on and off certain genes in organisms based on environmental conditions and pass those changes to offspring is called epigenetics. Epigenetics allows individual organisms to change their traits slightly to adapt to their environment. Where evolution by natural selection takes millions of years and results in the evolution of populations on a macro scale rather than individual organisms, epigenetic changes are much quicker.

Researchers were attracted to studying the winter skate fish in this bay because though the fish lies all along the North American coast, in this bay, the fish tends to be significantly smaller than other members of its species. Scientists attribute this to the warm water in this shallow water area which makes smaller organisms more likely to survive and reproduce.

However, DNA tests showed that significant changes in the genome of the fish weren’t what made them smaller, indicating it wasn’t Darwinian natural selection that dominated this process. The researchers discovered that the fish could turn on and off certain pieces of DNA in individual organisms to better adapt to the environment. Thus, the fish are able to adapt more quickly to changes in temperature than other organisms that rely solely on natural selection for changes to their traits.

Thus, Lamarck wasn’t entirely wrong all along (just mostly!).

The researchers hope this new information will help with conservation efforts and will give more insight into how species adapt to climate change.

So, do we owe Lamarck an apology? How can conservationists use this information to draw more interest to their goal?

Sperm Epigenetics and the Next Generation

Jerome Jullien from the Welcome Trust CRUK Gurdon Institute in Cambridge experimented with frogs to see if more than just DNA is passed on to the second generation offspring.  Sperm contain something called epigenetic tags which are “chemical switches attached to the genomes of sperm.”  (It is important to understand that epigenetics does not alter an organism’s DNA.)  In order to test if these sperm epigenetics influence offspring Jullien used two types of sperm; regular frog sperm and spermatids which had different epigenetic tags.  They then injected the sperm and spermatid into genetically engineered eggs which took away some of the epigenetic tags (with specific enzymes) on the sperm.  This lead to abnormal gene expression causing problems for the offspring.

This basically shows that a male does not simply pass down his DNA to his offspring but other factors like epigenetic tags can also effect the life of their kids.  As Jullien says, “The obvious implication is that whatever experiences the father has in life that end up epigentically modifying sperm cells might also be transmitted to the offspring and affect their genetic development and characteristics.”  There is still disagreement over whether epigenetic tags on sperm influence offspring.  For example some feel the experiment tested was not realistic because the frogs were not exposed to different environments as a human would be in his lifetime.  What do you think; would epigenetic tags on male sperm have an effect on a mans offspring?

Why Do We Have Five Fingers?

Have you ever wondered why we have five fingers? Why not four or six? Researchers at the University of Montreal have recently made a discovery that brings us closer to answering these questions.

 

This summer, researchers found that the two genes, hoxa13 and hoxd13, that are responsible for the formation of fingers in humans are also responsible for the formation of fin rays, the bonny parts of a fin that resemble webbed fingers, in fish. This exciting discovery demonstrates the evolutionary link between fins and fingers. It has been established that the limbs of vertebrates have evolved from fish fins, but now we have a direct genetic link between fish fins and human fingers to prove the connection.

 

While this discovery filled in an important gap, there were still unanswered questions. Fossils indicate that our ancestors had more than five fingers, so how did humans evolve to only have five?

Using this new information, a research team from the University of Montreal discovered that during development, the hoxa11 and hoxa13 genes are activated together in overlapping domains in order to develop fins. Conversely, in human development, these genes are activated in separate domains, forming individual fingers. Following this discovery, the researchers performed an experiment on mice, in which they activated the hoxa11 and hoxa13 genes in overlapping domains, similar to the process that takes place in fish. As a result, the mice developed either six or seven fingers per paw, illustrating that the evolution of our hands did not occur from the acquisition of new genes, but the modification of how they are expressed.

 

While this discovery helps us move closer to figuring out the history and process of our evolution, it also helps us understand how mutations form. These findings further explain how malformations during fetal development occur not just from genetic mutations, but also mutations in regulatory sequences.

Disruption in Epigenetics Can Lead to Cancer

Epigenetics is the study of potentially inheritable gene expression that does not involve any changes to the underlying DNA sequence. Epigenetic change is natural and common, but can be brought on by changes in environment, age, lifestyle, etc. Epigenetic modifications are seen as cells terminally differentiate and end up as skin cells, brain cells, or even liver cells. Epigenetics is a constant battle between active and inactive genes. If one were to overtake the other, it would alter the equilibrium in a persons body, potentially causing cancer.

Scientists are now claiming that once they have a better understanding of epigenetics and the factors which cause the cancer, they will be able to design drugs to counter this loss of equilibrium. Recent data identified an epigenetic “writer” called methyltransferase EZH2. It’s been linked to several types of cancer including melanomas and lymphomas. They’ve also identified and epigenetic “eraser”, KDM3A, which takes on an oncogenetic role and activates tumor promoting genes in the body. Epigenomic changes also contribute to cancer’s ability to go undetected in the human immune system.

Using this information, researchers may have found the right pathway for drug targeting. Metabolites and epigenetics are tightly connected and rely on each other to stay in equilibrium. In addition, there is a strong cooperation of epigenetic factors with the transcriptional complex. Now, researchers are looking into finding a way to us this connection to suppress tumor causing epigentics, and amplify those that fight cancer.

Fabian V. Filipp, the author of the paper, states, “There is an intriguing crosstalk between metabolism and epigenetics… With both fields maturing, further synergy between epigenetic and metabolomics may deliver new therapeutic agents.”

This research is incredibly interesting because of its newness. Each day, new informatoin and research is being found in the field of epigenetics. What I would’ve liked to learn in this article is how they plan to use the metabolites to battle the cancerous cells, and in what way they would be administered. Each day we get closer to the answers. The new technology and knowledge of today may finally lead us to a cure or at least a way towards remission with certain types of cancer.

Image result for cancer epigenetics

Source article: https://www.sciencedaily.com/releases/2017/03/170324083018.htm

Playing God: New Technology Gives Scientists the Ability to Delete DNA

Since the relatively recent discovery of CRISPR-Cas9, scientists have explored multiple uses of this new technology, from eliminating a patient’s cancer to making super plants, furthering our understanding of DNA and how it works. CRISPR-Cas9 has become the most advanced and efficient gene-editing tool there is. However, thus far, its use has been largely limited to silencing protein-coding genes in the DNA. This leaves out what’s called the DNA “dark matter” — the non-coding DNA that covers about 99 percent of our genetic code. That’s about to change; this article from Futurism explains how a recent study from PLOS Computational Biology is creating a new technique, based on CRISPR, but delving deeper into this unexplored territory.

This brand-new software technology called CRISPETa evolved from a breakthrough tool (which uses CRISPR-Cas9) called DECKO. DECKO was designed for deleting pieces of non-coding DNA using two sgRNAs as molecular scissors. While the concept might seem simple, designing deletion experiments using DECKO was time-consuming due to the lack of software to create the required sgRNAs.

This is where the new tool, CRISPETa, comes in. According to the report, users can tell CRISPETa which region of DNA they wish to delete. The software then generates a pair of optimized sgRNAs that can be used directly for that experiment. Pulido, leader of the research team, stated that “We hope that this new software tool will allow the greatest possible number of researchers to harness the power of CRISPR deletion in their research.”

The software has already demonstrated its efficiency in deleting desired targets in human cells. The research team hopes that its use will go beyond a basic research tool, and be utilized as “a powerful therapeutic to reverse disease-causing mutations,” Johnson added. Herein lies the hidden value of CRISPR-Cas9 and all further developments from it: The more we understand DNA and genomics, the better we will be able to fight diseases and other aspects of human life that cause harm, ultimately leading to a higher quality of life for all.

 

Anti-CRISPR Proteins: What are they and can they be beneficial?

NIH Image Gallery Image Link

Understanding CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)

For many bacteria, one line of defense against viral infection is the RNA guided “immune system” known as CRISPR-Cas. This particular complex is unique because of its ability to recognize viral DNA and trigger its destruction. Scientists have used CRISPR to degrade sections of viral RNA and use the CRISPR systems to remove unwanted genes from an organism. CRISPR proteins have also been studied with the hope of eliminating serious disease and illnesses. However, this CRISPR system does not always work do to anti-CRSPR proteins that inhibit the complex from working properly.

Research 

According to an article on ScienceDaily, researchers have finally discovered how these anti-CRISPR proteins work! Research done by biologist Gabriel C. Lander from the Scripps Research Institute, discovered that anti-CRISPR proteins work by inhibiting CRISPR’s ability to identify and attack viral genomes. Just like there are different CRISPR systems, there are multiple anti-CRISPR proteins as well. One in particular mimics DNA to throw the CRISPR-guided detection machine off its course. Scientists have been able to further discover certain aspects of CRISPR and anti-CRISPR systems by using a high-resolution imaging technique called cryo-electron microscopy. They have discovered that the CRISPR surveillance complex analyzes a virus’s genetic material to see where it should attack by having proteins within the complex wrap around the CRISPR RNA, exposing specific sections of bacterial RNA. These sections of RNA then scan viral DNA, looking for genetic sequences they recognize. Lander describes these proteins as being very clever because they “have evolved to target a crucial piece of the CRISPR machinery. If bacteria were to mutate this machinery to avoid viral attacks, the CRISPR system would cease to function.” Therefore, CRISPR systems cannot avoid anti-CRISPR proteins without completely chancing the mechanism used to recognize DNA. Another type anti-CRISPR protein works a bit differently. Based on its location and negative charge, this anti-CRISPR protein acts as a DNA mimic, fooling CRISPR into binding this immobilizing protein, rather than an invading viral DNA.

Can Anti-CRISPR Proteins be beneficial?

Researchers are saying that the understanding of how these anti-CRISPR proteins work are extremely important! According to an article on GEN, the discovery and understanding of anti-CRISPR proteins actually allows researchers to have greater control over gene-edits. In this article, Dr. Sontheimer, a professor in the RNA The RNA Therapeutics Institute at UMass Medical School, expressed how “CRISPR/Cas 9 is a good thing because it introduces specific chromosome breaks that can be exploited to create genome edits, but because chromosome breakage can be hazardous, it is possible to have too much of a good thing, or to have it go on for too long.” Anti-CRISPR proteins can be beneficial and work as an off switch for CRISPR, therefore advancing gene editing!

 

 

 

HIV Adapts to CRISPR-Cas9 Treatment

There has been an abundance of research using CRISPR/Cas9 gene editing to search for a cure for HIV. The HIV virus enters immune cells and uses the host cell’s method of replication to replicate the viral genome. With CRISPR/Cas9, specific mutations can be introduced in order to make it more challenging for the HIV virus to enter Helper T-Cells. Guided by specific strands of RNA, the Cas9 enzyme can cut a particular piece of the viral genome out, rendering it useless.

When a team of researchers at McGill University attempted to use the CRISPR method to disable the HIV viral genome, they found a major roadblock. Two weeks after the CRISPR/Cas9 treatment, the host cells appeared to be creating copies of the virus. This may be attributed to an error in the enzymes that copy the viral DNA, causing a change in the genome, and a mutation that allows it to evade the CRISPR treatment. However, the McGill researchers believe that this mutation was a result of the CRISPR treatment itself.

After DNA is cut by the Cas9 enzyme, the host cell usually attempts to repair the damage. Occasionally, this results in the addition or deletion of a few nitrogenous bases. While these changes usually result in the inactivation of the cut gene, sometimes they don’t. The active cut DNA is no longer recognized by the machinery used to prevent HIV infection of the cell, and the mutated viral genome is resistant to the usual methods of disablement.

More researchers at the University of Amsterdam had similar results in their research. While it is not that surprising that HIV can overcome the CRISPR/Cas9 gene editing at some point, the leader of the research (Atze Das) said “What is surprising is the speed- how fast it goes”.

If CRISPR was used at the same time as HIV-attacking drugs (inhibitors of protease, reverse transcriptase, and integrase), perhaps the mutations would be less  detrimental. This roadblock does not mean that a CRISPR cure for HIV is impossible, but it does make it far more challenging to overcome.

The Mystery of Epigenetics

Epigenetics, the process of altering what genes are activated in a certain DNA sequence, is in many ways, still a mystery to the scientific community. How it is done chemically, as well as what environmental factors cause it. New discoveries have been made, linking surprising regulation enzymes and cultural factors. Ultimately, no matter what causes this phenomenon, it is a key factor in the evolutionary development of many species, and the world as we know it.

Tryptase:

A new study has shown the role of the enzyme tryptase in epigenetic development. Tryptase works to cleave the tails of histones, which will stop some epigenetic changes, while cells that lack tryptase, begin to proliferate uncontrollably. Most importantly, this proliferation causes cells to lose their identity. With this discovery, we see that by introducing tryptase, we can influence epigenetic development in cells.

Culture:

Another recent study has shown that cultural and environmental factors can influence a genome rather than only genetic ancestry. By studying the genetic sequences of both Mexican and Puerto Rican children, researchers discovered that there were differences that couldn’t be accounted for by ancestry.   The rest may be an impact on genetic makeup by differences in experiences, practices, and culture distinct to the two ethnic subgroups.

Ultimately, epigenetics is a fascinating concept that is often influenced by factors we might not suspect.   As the scientific community continues to make discoveries, the epigenetic phenomenon continues to excite and inspire researchers.

Photo: https://www.sciencedaily.com/releases/2017/01/170110120638.htm

The Role of Metabolism and Epigenetics in Cancer Development

Cancer most commonly is defined as a “perpetuating mass of dystregulated cells growing in an uncontrolled manner”, however the meaning can be further related to epigenetics, for they appear to be very much interconnected.  Another definition of cancer goes on to note this relationship as the “dynamic genetic and epigenetic alterations that contribute to cancer initiation and progress.” Recent research shows that if epigenetics is disrupted, it might switch to oncogenes or shut down tumor suppressors. Either way, this would lead to the development of tumor cells that would cause cancer. We are already aware of the fact that chemical modification affecting the packaging of our DNA can switch genes on and off. The first time that became aware of an epigenetic code, we learned that that code chemically labels active or inactive genetic information. The focus of epigenetics is on the change caused by the modification of gene expression, not the alteration of the code itself. With recent discoveries through research on epigenetics and its relation to cancer, we learned that there must be a balance of “writers” and “erasers” for the cells. Recent data has shown that methyltransferase EZH2 is an epigenetic writer that is hyperactivated in many cancers, specifically melanomas and lymphomas. This recent research also shows KDM3A (member of the jumonji histone lysine demthylase family) as an epigenetic eraser. KDM3A fulfills an oncogenic role by activating a network of tumor promoting genes. Epigonomic changes also allow tumor cells to evade the immune system so that these cells can thrive and divide without the disruption of the immune system. Ultimately, there are two potential pathways that epigenomic regulators can cause cancer. The first is the result of too much epigenetic activation, which can lead to oncogenes. The second is too much epigenetic protection that conversely blocks tumor suppressor genes. DNA hypermethylation causes the silencing of tumor suppressor genes.

Both of these methods would lead to the development of cancer. Epigenetic regulation involves methods including histone regulation, DNA methylation, and changes in noncoding RNAs such as miRNAs. One of the challenges of studying cancer and researching possible vulnverabilities in pathways is that they are often disrupted by epigenetics. The recent studies also have shown that there are close ties between epigenomic (analysis of global epigenetic changes across many genes) changes and metabolites, or human cellular chemistry. Metabolites initiate, target, or maintain epigenetic factors with the transcriptional complex, and cooperation with them metabolites can target, amplify or mute these coded responses. Since the fields of both epigenetics and metabolism are still developing a great deal, there is hope that these insights with regards to cancer and regulating gene expression to prevent the development of cancer will allow for more precision in targeting cancer, specifically when existing methods of therapy fail to work sufficiently.

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