AP Biology class blog for discussing current research in Biology

Author: margauxylgroup

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.

A Good Night’s Rest is More Important than We Thought: Decreased Slow-Wave Sleep Linked with Alzheimer’s Disease

Whether it be a quick nap or a nighttime full of sleep, I love sleep. However, with a busy schedule and tons of commitments, I find myself prioritizing these events over my own rest. How much do these short-term habits affect your long-term health?

It has been noted that poor sleep is a telltale symptom of Alzheimer’s disease. As the disease progresses, people tend to wake up tired and their sleep becomes less refreshing. But, is unclear how and why restless nights are linked to Alzheimer’s disease. However, researchers at Washington University School of Medicine in St. Louis may have discovered part of the explanation.

Alzheimer’s disease affects approximately 5.7 million Americans, and the brain changes appear slowly and silently. Up to two decades before the characteristic signs of memory loss and confusion appear, amyloid beta protein begins to build up into plaques in the brain. The brain protein tau appear later, then atrophy of the key brain areas next. It is after all of these internal and unnoticeable changes that people start to show unmistakable symptoms of cognitive decline. But, what if there were a way to find the symptoms earlier?

The researchers at Washington University in St. Louis found that older people who have less slow-wave sleep, the deep sleep your body needs to consolidate memories and wake up feeling energized, have higher levels of the brain protein tau. Elevated levels of it has been linked to brain damage and cognitive decline, such as in Alzheimer’s. The relationship between sleep, the tau protein, and Alzheimer’s marks great strides in diagnosing and helping patients with the disease. Brendan Lucey, MD, an assistant professor of neurology and director of the Washington University Sleep Medicine Center believes that “measuring how people sleep may be a noninvasive way to screen for Alzheimer’s disease before or just as people begin to develop problems with memory and thinking.”

Decreased slow-wave sleep and increased production of the tau and amyloid proteins have been linked to Alzheimer’s disease.

The study examined 119 people 60 years of age or older. Researchers monitored the participants’ sleep through a portable EEG monitor that strapped to their foreheads to measure brain waves, as well as a wristwatch-like sensor that tracked body movements. Participants also kept sleep logs, making note of both nighttime sleep and daytime naps. Additionally, researchers measured levels of amyloid beta and tau in the brain and spinal fluid. The results found that decreased slow-wave sleep coincided with higher levels of tau and amyloid. Lucey remarked that “the key is that it wasn’t the total amount of sleep that was linked to tau, it was the slow-wave sleep, which reflects quality of sleep. The people with increased tau pathology were actually sleeping more at night and napping more in the day, but they weren’t getting as good quality sleep.” In fact, daytime napping was significantly associated with high levels of tau.

This newfound information concludes that sleep monitoring may be an easy and affordable way to screen earlier for Alzheimer’s disease. Doctor’s may be able to ask a simple question: “How much do you nap during the day?” to identify people who could benefit from further testing. Overall, this study shows that regardless if you have Alzheimer’s or not, it is important to get enough slow-wave, deep sleep, or else you may reap the consequences later in life.

Brain Disorder is Closely linked to… the Microbiome?

Parkinson’s disease and the gut microbiome. Two seemingly different topics are actually more related than meets the eye. 

Parkinson’s disease is a neurodegenerative disorder that effects dopamine-producing neurons in the brain. Physical effects of Parkinson’s include tremors, bradykinesia, and limb rigidity. Even though Parkinson’s is the 14th leading cause of death in the United States, the cause and cure remain largely unknown. 

However, a recent study done at the University of Alabama at Birmingham has discovered that there is a link between Parkinson’s disease and the bacteria in the gut microbiome. The gut microbiome contains tens of trillions of microorganisms that are apart of our immune system and metabolism. Approximately one third of the bacteria are common to most people, while the remaining two thirds are specific to oneself and their body. These organisms serve as our own “identity card” that makes us unique. Haydeh Payami, Ph.D., professor in the Department of Neurology in the University of Alabama at Birmingham School of Medicine who lead the study remarked that “the collective genomes of the microorganisms in the gut is more than 100 times larger than the number of genes in the human genome. We know that a well-balanced gut microbiota is critical for maintaining general health, and alterations in the composition of gut microbiota have been linked to a range of disorders.” More specifically, the microbiome helps rid the body of xenobiotics, or chemicals not naturally found in the body often arising from environmental pollutants.

Payami concluded that the research “showed major disruption of the normal microbiome … in individuals with Parkinson’s.” The study followed 197 patients with Parkinson’s from three distinct regions in the United States: New York, Atlanta, and Seattle. Research indicated that patients living in different regions had different gut imbalances, which may reflect the environmental, lifestyle and diet differences between the locations. The study also found that certain medicines used to treat Parkinson’s interact with the gut microbiome differently. It was also noted that the bacteria responsible for removing the aforementioned xenobiotics was different in individuals with Parkinson’s. However, it is still unclear whether Parkinson’s causes changes in an individual’s gut microbiome, or if changes in the microbiome are an early warning sign of the disease. 

The human gut microbiome from this source

Research between the gut microbiome and Parkinson’s is relatively new, so there are no concrete findings or cures yet. Fortunately, this study may hold information for assessing the efficiency or toxicity of medication for the disease by examining its effects in the microbiome. As someone whose relative battled Parkinson’s, I have firsthand witnessed the effects of this terrible disease. It is reassuring to see that there is new research being done every day to eventually find a cure, but in the meantime making the lives of those fighting Parkinson’s easier. As Payami said, “This opens up new horizons, a totally new frontier.”

To read the full study, click here. What do you think: Does Parkinson’s disease change the microbiome or is a change in the microbiome an early indicator of the disease?

Just Add Water: Water’s Importance in Protein Folding

It’s amazing that two hydrogens and an oxygen atom is the basis of life. We are made of 60% of this simple compound, water, and is necessary for repairing cells, tissue, and keeping our organs functioning properly.

According to research published in the Proceedings of the National Academy of Sciences, water is why amino acids fold into their proper shapes. Amino acids are considered the building blocks of life and compose proteins. To delve further into the structure and function of amino acids, click here. Dongping Zhong was the leader of the research group and made the breakthrough discovery of water-protein interaction. He used laser pulses to take snapshots of water molecules moving around a DNA polymerase- the enzyme that helps DNA reproduce. Zhong observed that the water directly interacted with the R groups, the part of the amino acid that attach and detach with other amino acids to fold and direct the protein’s function.


Photo Credit:

It is important to note, however, that water is not the only factor in determining protein shape. Proteins can only fold and unfold in a few different ways, which depend on the amino acids they are comprised of. Nonetheless, water and amino acids themselves are the two reasons for DNA replication and the dozens of other activities that proteins take part in. Zhong’s discovery is just an homage to the larger role of water in everyday life: by just adding water, life runs smoothly.

If this information doesn’t convince you to drink more water, read about the molecular changes our body experiences with lack of water, or when we are dehydrated.

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