BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: Gene expression

Can We Alter Mammals Social Behavior Using CRISPR Gene Editing Mechanisms?

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On April 30, 2023

In Student Post

At Georgia State University a team of researchers led by professor H. Elliott Albers and Professor Kim Huhman put gene editing mechanisms to the test to determine if it was possible to alter hamsters behaviors. The hamsters that were utilized in this experiment were Syrian hamsters. These hamsters have been extremelGolden hamster front 1y important in many scientific experiments that look into social behaviors, aggression and communication. Furthermore, hamsters are widely used in scientific research due to the fact that their social skills resemble most similarly to humans.

 

In this experiment, professor H. Elliott Albers and Professor Kim Huhman utilized CRISPR-Cas9 technology to deactivate neurochemical signaling pathways that play a major part in controlling mammalian social behaviors. The regulators of the social phenomena that controls pair bonding, cooperation, social communication, dominance and aggression are the hormone vasopressin and the receptor it acts on, Avpr1a. VasopressinSek

After the gene editing and the observation of the hamsters were complete, the researchers were shocked by their unexpected results. As stated by Professor H. Elliott Albers,  he “anticipated that if we eliminated vasopressin activity, we would reduce both aggression and social communication. But the opposite happened.”

Instead of reducing the hamsters’ aggression and social communication, the absence of the receptor that activates the vasopressin led the hamsters to demonstrate increased levels of social communication behaviors than when observed prior to the gene editing. Furthermore, it was observed that the differences in opposite sex aggression were removed. Both the male and female hamsters showed aggression towards other same-sex hamsters.  

This shocking finding led the researchers to a different conclusion than foreseen. Because it is known that vasopressin correlates with the increase of social behaviors, it can be concluded that the Avpr1a receptor is inhibitory. 

Moreover, confirming this study done at Georgia State University, another study published in the Proceedings of the National Academy of Sciences, finds that that eliminating the Avpr1a receptor in hamsters windes up deactivating the vasopressin’s action on the receptor, therefore changing the social behavior of the hamsters drastically in ways one would not expect.

Overall, Professor H. Elliott Albers contends that this study is of extreme value as it helps researchers understand the“neurocircuitry involved in human social behavior and our model has translational relevance for human health. Understanding the role of vasopressin in behavior is necessary to help identify potential new and more effective treatment strategies for a diverse group of neuropsychiatric disorders ranging from autism to depression.”

Connection to AP Biology 😀

This study is connected to our AP biology class as we have learned about regulation of gene expression. Without the presence of the Avpr1a receptor, the vasopressin has no way to be mediated, thus enhancing its social behavioral effects. And with the presence of the Avpr1a receptor, the vasopressin is still active, however, muted. 

Maternal Stress During Pregnancy

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On April 30, 2023

In Student Post

According to researchers at the University of Cincinnati, maternal stress during pregnancy has a harmful effect on the neurodevelopment of babies. A methyl group gets added to DNA, which is called DNA methylation. This likely plays a role in it. The findings could provide new insight into how the fetal environment potentially influences neurodevelopment, metabolism, and immunologic functions. 

DNA methylation

More than 5,500 people took part in this study, which broke down into 12 different groups. The research examines financial stress, conflict with a partner, conflict with a family member or friend, abuse, and death of a friend or relative. Plus, there is a cumulative score that combines all these categories. 

Two young people demonstrating combat

They found that mothers experienced a great amount of stress during pregnancy. There was an association with DNA methylation in the umbilical cord blood, which is an epigenetic modification in the baby’s development. They found five specific locations of DNA methylation with three different maternal stressors. The three different maternal stressors were conflict with a friend or family, abuse, and death of a close friend or relative.  

Epigenetics modifications

In AP Biology, we have learned that DNA methylation causes nucleosomes to pack tightly together, which prevents transcription factors from binding to the DNA. Gene expression is the process of turning on a gene to produce protein and RNA. 

The researchers plan to further investigate and do some functional analyses to see how the genes work and how the DNA methylation affects their expression. 

 

CRISPR corrects genetic diseases in mice!

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On March 20, 2022

In Student Post

Researchers at Duke University have shown that a single systemic treatment using CRISPR genome editing can safely correct Duchenne muscular dystrophy (DMD) in mice for over a year. In 2016 the first successful use for CRISPR to treat an animal model of a genetic disease was published by, Charles Gersbach, the Professor of Biomedical Engineering at Duke. The strategy used by Gersbach can potentially be used for human therapy.

 

Since 2009, Gersbach has been working on finding a genetic treatment for DMD and his lab was one of the firsts to focus on CRISPR, which is a defense system that slices apart the DNA of invading viruses.The goal was to cut out the dystrophy exons around the mutation and then let the body naturally repair the DNA and stitch it back together to create a shortened dystrophy gene. After eight weeks it was observed in the mice used for the experiment that functional dystrophin was restored and muscle strength increased but the long term effects of the treatment had not been explored.

GRNA-Cas9

The new goal of Gersbachs study was to figure out these long term effects. To determine this, doctor Christopher Nelson gave both adult and newborn mice with the dystrophy gene a dose of CRISPR. The mice were monitored over the year to see what kind of genetic alterations were made as well as any immune responses. There were no results of toxicity in any of the mice. Although this is a positive result Gersbach and Nelson know that a mouse immune system can function differently than a human immune system which brings further questions of reliability of CRISPR in humans to the table.

 

In my AP biology class we recently learned about gene expression. CRISPR systems have been engineered to control gene expression in bacteria. CRISPR is used to target precise parts of DNA which could help to correct abnormalities that cause diseases.

Bacteria Not So “Bad”, After All?

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On January 18, 2018

In Student Post

Photo Link: Wild Garden of Gut Bacteria, By: Nicola Fawcett

Most of us are used to the common notion that bacteria may not be the most beneficial factor in maintaining your health.  Thats why the results of a recent research study conducted by scientists at Babraham Institute in collaboration with colleagues in Brazil and Italy, yielding evidence that in fact good bacteria in the gut can control gene expression in our cells, is game-changing!

The research team, led by Patrick Varga-Weisz, made this discovery by studying the gut bacterias found within various mice. Their attention was quickly drawn to the mice that had lost most of their gut bacteria. It became apparent that in the mice with a very low amount of the bacteria within their gut, contained increased amounts of the “HDAC2 protein”.  When investigating deeper into HDAC2, it was found that increased amounts of this particular protein are associated with increased risk of colorectal cancer.

This new research also resulted in the finding that the amount of chemical markers on our genes, are increased by short fatty acids. These specific chemical gene markers, known as “crotonylations”, were only recently discovered and are newly classified as genome “epigenetic markers”. The researchers then found that by shutting down the HDAC2 protein, short chain fatty acids increase the number of crotonylations.

Ingestion of fruits and vegetables into ones healthy diet are vital – ultimately determining how chemicals produced by gut bacteria, affect genes in the cells of the gut lining. In other words, the short fatty acids, which come from those dietary elements, have the ability to move from bacteria into our own cells, and from there cause changes in gene activity and cell behavior.

In the end, the scientists were strongly convinced that the ability to turn off and on genes, is determined by changes in crotonylation. This inferred that the existence of crotonylation in the genome of cells is vital to protect the body from cancer. Therefore, the pretense of good bacteria is very important for the prevention of disease and illness in the body!

As someone with a strong passion for the science, and also very influenced and intrigued by medicine, I very much enjoyed this study. As the boundary to curing cancer is still a hurtle doctors and scientists try to transcend everyday, studies like these, are both hopeful and fascinating, to me. Also, as someone curious about how the human diet ultimately affects the functions and inner workings of the body, this research again was very engaging and interesting!

Primary Source Article: How good bacteria controls your genes

Secondary Source: Wikipedia – Gut Flora (Gut Bacterias)

 

The Difference between You and a Chimpanzee!

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On December 10, 2017

In Student Post

The largest difference between you and a chimpanzee or a monkey can be found in the brain. Despite the fact that all regions of the human brain have very similar molecular signatures to your primate relatives, a new study has found that these regions contain distinct human patterns of gene activity that mark the brain’s evolution. This new study may contribute to our cognitive abilities.

Although human brains are three times larger and have many more cells and therefore more processing power than a chimpanzee, researchers, Zhu and Sousa, have found similarities between humans and our primate relatives in gene expressions in 16 regions of the brain.  A gene similarity was even found in the prefrontal cortex, a place where higher order learning takes place that most distinguishes humans from other apes. However researchers have also found that the striatum had the most human-specific gene expression, a region most commonly associated with movement.

A surprising difference was found in the cerebellum, one of the evolutionarily most ancient regions of the brain, and therefore most likely to share similarities across species. Researches found the gene ZP2, a gene active in only the human cerebellum, which is surprising considering the same gene has been linked to sperm selection by human ova. Zhu, a postdoctoral researcher, says that they, “have no idea what it is doing there.”

Researchers Zhu and Sousa have focused on one gene, TH, which is involved in the production of dopamine. TH is a neurotransmitter crucial to higher-order function and depleted in people living with Parkinson’s disease. They found that TH was highly expressed in human neocortex and striatum but absent from the neocortex of chimpanzees.

This research could be important in finding the cure to certain diseases like Parkinson’s disease. Also would be helpful in understanding how the human mind processes higher-order actions.

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

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On April 5, 2017

In Student Post

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 Gene Switch

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On March 10, 2015

In Student Post

Researchers at the Stowers Institute for Medical Research have created a high-resolution mechanism to “precisely and reliably map individual transcription factor binding sites in the genome.” This new technique, published in Nature Biology today, has proven to be more efficient and successful than those previously studied.

All of the cells in an organism carry DNA; however different cells in the body express different portions of it to function properly. For instance, nerve cells express genes that facilitate them carrying messages to other nerve cells. This process is known as gene expression and is responsible for making our bodies function the way we do. Despite our limited knowledge on gene expression, researchers are aware that it is is controlled by proteins called transcription factors that bind to specific sites around a gene and,  in the right order, allow the gene’s sequence to be read.

Transcription factor binding sites in DNA are extremely difficult to locate but, thanks to new technology, it is becoming easier to track their location. “The transcription factor binding sites that are likely functional leave behind clear footprints, indicating that transcription factors consistently land on very specific sequences. In contrast, questionable binding sites that were previously detected as bound showed a more scattered unspecific pattern that was no longer considered bound.”

These techniques are implemented through a method called chromatin immunoprecipitation or ChIP, a tool that determines the relativity of the proteins to their positions on the DNA, cuts the DNA into reasonable sizes, and then isolates the sections that are bound by the proteins. While the research is largely preliminary, scientist Zeitlinger attests to the significance of this creation; ”If we do this kind of analysis for lots of transcription factors, we will gather information needed to better understand gene expression.”

chIP

chIP mechanism

The Harm Stress Causes

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On March 10, 2015

In Student Post

http://upload.wikimedia.org/wikipedia/commons/c/c6/DNA_double_helix_45.PNG

https://www.sciencenews.org/article/chronic-stress-can-wreak-havoc-body

Recently scientists have begun to discover why stress can have a negative effect on the human body. Although stress is needed when dealing with situations which require hormones to trigger a fight or flight, consistent stress can lead to a multitude of health problems. Chronic stress can lead to mental instability, and an increased risk in heart attacks, strokes, infection, etc. The decrease in health is due to inflammation and warped genetic material caused by epigenetics (chemical interactions that activate and deactivate regions of a genome to carry out specific functions). Recently scientists have discovered that  changes in epigenetics can affect activity levels in genes which directly change responsibilities of certain cells including immune cells. The stress causes a genetic response that deactivates certain areas of a genome which stops an immune cell from working properly, which of course leads to an increase in diseases that cannot be properly taken care of. Hopefully, as we continue to understand epigenetics, we will be able to take appropriate steps that will both further our understanding of the human genome, as well as help increase the longevity and immune system of individuals.

Save the Devils

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On March 11, 2013

In Student Post

When most people hear the name Tasmanian Devil, they think of the small and ferocious little animal from the Looney Tunes named Taz. Just like in the show, Tasmanian Devils (carniverous marsupials)  are tough, rugged and very aggressive animals. Unfortunately, over the past two decades, a rare case of contagious facial cancer, with a 100% mortality rate, has decimated the population. Scientists have estimated that this specific cancer has wiped out about 85% of the entire population, almost to the point of extinction. The cancer is typically spread when the Devils bite each other in the face during battle, killing it in a matter of months. Scientists are working tirelessly to find out how this cancer is slipping by the immune system and hope to find a cure.

Until recently, scientists believed that the cancer was able to develop, without

being detected by the immune system, because Tasmanian Devils lack genetic diversity. However, a study led by the University of Cambridge claims it is much more complex. On the surface of most cells are histocompatability complex (MCH) molecules, which determine whether other cells are good or bad. If the cell happens to be a threat, then the cell triggers an immune response. According to the research, these DFTD cancer cells lack theses complexes and can therefor avoid detection.

Researchers also found that the DFTD cells have just lost the expression of MCH molecules and that its genetic code is still in tact (it can be turned on). By introducing specific signaling molecules, scientists believe they can force the DFTD cells to express these molecules, leading to the detection of the cancer. Not only will this research help save the Devils, but it will also give scientists a head start on contagious cancers in other species when the time comes.

Breakthrough in Epigenetics!

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On March 18, 2012

In Student Post

 

This file (Arabidopsis thaliana flower) is in public domain, not copyrighted, no rights reserved, free for any use

 

For several dozen years scientists have searched for a way to understand the role of a single RNA strand in gene expression.  Scientists have been without a method to pinpoint 1 type of RNA strand and isolate its effect thus discovering its influence and its corresponding proteins role in influencing the way our bodies work.

However a breakthrough was made this march regarding such obstacles.  A team of scientists from Michigan Technological University discovered a way to turn off small RNA strands in order to figure out what they are up to.  They did this by inserting their own custom DNA strand that codes for something called a small tandem target mimic or “STTM” into a plant known as “Arabidopsis“.  Inside the plant, these DNA strands gave rise to STTM’s that blocked the ability of a target RNA to express itself.  The particular target for the STTM was a type of RNA strand suspected to be involved with facilitating vertical growth of the plant.  The STTM’s stopped the RNA from being able to cut itself into smaller bits, and prompted the target RNA’s to destroy all of its own smaller RNA’s that would normally slice the target RNA.  This effectively lead to the disappearance of the target RNA’s protein products thus resulting in no expression of the gene the target RNA from transcribed from.

The result was outstanding.  “The control Arabidopsis plants grew upward on a central stem with regularly shaped leaves and stems. The mutant plants were smaller, tangled, and amorphous.”

The above process is said to be “a highly effective and versatile tool” for studying the functions of small RNA.  One researcher on the team who discovered this method stated that she intends to use this discovery to study type 2 diabetes.

 

Reference

http://www.sciencedaily.com/releases/2012/03/120301143756.htm

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