BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: protein

If You Give A Mouse…Sight!

In a recent study published in the Journal Of Experimental Medicine, researchers in China successfully used CRISPR Gene-Editing technology to restore sight to mice with retinitis pigmentosa.

That’s a lot of vocabulary all at once, so let’s establish some definitions first and foremost.  According to the National Eye Institute, retinitis pigmentosa is a “genetic disease that people [and animals] are born with…that [affects] the retina (the light-sensitive layer of tissue in the back of the eye)”. As for CRISPR Gene-Editing technology, YG Topics defines it as, “a unique technology that enables geneticists and medical researchers to edit parts of the genome by removing, adding or altering sections of the DNA sequence”.

Most inherent forms of blindness and loss-of-vision stem from genetic mutations, and thus retinitis pigmentosa is one of many forms of genetically caused blindness.  However, through CRISPR technology, the researchers in the study successfully edited the DNA of mice who had the mutation to eliminate retinitis pigmentosa and give them the ability to see.  The results of the study are very promising, as not only does retinitis pigmentosa affect mice, but human beings.  Thus, there is evidence that CRISPR could be used to cure blindness among everyday people.  Kai Yao, a professor from the Wuhan University of Science and Technology who contributed to the study said, “The ability to edit the genome of neural retinal cells, particularly unhealthy or dying photoreceptors, would provide much more convincing evidence for the potential applications of these genome-editing tools in treating diseases such as retinitis pigmentosa”.

In AP Biology, we discussed how DNA factors into the traits of a living being.  DNA is made up of 3 base codons that form up to 20 different amino acids.  These amino acids code for specific proteins.  Through a process of DNA transcription and translation, the DNA uses various forms of RNA to code for proteins, which help tell the cell what to do.  Thus, the way the cell acts is largely determined by its DNA.  Essentially, DNA codes certain traits through various amino acid sequences.  Mutations and alternations to amino acid sequences cause different traits, such as red hair, blue eyes, or blindness.

Thus, successfully altering the DNA of mice has huge implications for the human race.  CRISPR could potentially be used to edit the DNA of humans, and thus help limit and prevent certain genetic conditions.  Many diseases are based on genetic mutations, and if CRISPR Gene Editing technology is proven successful, we could potentially eliminate genetic diseases in a few decades.  While “much work still needs to be done to establish both the safety and efficacy” of CRISPR technology, some groundbreaking scientific treatments could be coming sooner than you think (Neuroscience News).

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The Fluorescent Frontier: Glow in the Dark Proteins in Disease Research

We all know that although science is improving rapidly on a global scale, diagnostic tests for diseases remain sensitive and require complicated techniques. One evident example is the tests for COVID-19. This complexity can range from their preparation to an interpretation of their results. However, recent research from the American Chemical Society has developed a method that is able to analyze viral or infected nucleic acids in less than 30 minutes and in just one step. This is all due to “glow in the dark” proteins.

Bioluminescence is a scientific phenomenon that powers many animals: a firefly’s flash, an anglerfish’s glowing head, and even phytoplankton’s blue color.  Here a chemical reaction occurs, involving the luciferase protein. This protein essentially causes the “glow in the dark” effect. The protein is incorporated into sensors which emit a light when a target is located. Although the simplicity of these sensors is idyllic for clinical diagnostic testing, they still lack the sensitivity

One solution to this problem is presented by a particular gene editing technique: CRISPR. The Broad Institute defines CRISPR as; Clustered Regularly Interspaced Short Palindromic Repeats. It is essentially an efficient and customizable alternative to other existing genome editing tools. With this new technique, Maarten Merkx and his coworkers wished to use CRISPR-connected proteins while combining them with a bioluminescence form whose glow could be seen by humans, through a digital camera for example.

CRISPR CAS9 technology

To ensure that there was an ample amount of DNA or RNA to analyze, they used a technique known as Recombinase Polymerase Amplification, or RPA. This is a simple method which works continuously at a temperature of 100 F. With this  two CRISPR proteins specific for different parts of a viral genome each have a different fragment of luciferase attached. In other words, the new treatment known as LUNAS (Luminescent Nucleic Acid Sensor), takes two CRISPR proteins for different parts of a viral genome and has a distinct fragment of luciferase added to each.

Moreover, if one specific viral genome that the researchers were testing was present, the two CRISPR proteins would bind to the targeted nucleic acid sequence. This would allow them to come together and promote the full luciferase protein to form and glow. Additionally, to account for the luciferase being depleted, the researchers used a control reaction which turned green. In the event of a positive viral detection the color would change from green to blue. To prove the validity of this method, the researchers tested LUNAS on clinical samples of nasal swabs testing COVID-19. The method successfully detected the virus in less than 20 minutes, even at low concentrations. With this, the LUNAS method holds great potential in detecting other viruses in a concise and efficient manner.

Zika-chain-colored

To connect to our AP Bio class, we learned about how specific proteins code for specific actions or results in our bodies. At their tertiary and quaternary structures, proteins have a myriad of functions ranging from acting as a receptor to interacting with an enzyme. This parallels with the luciferase’s specific function of creating a glow affect. Additionally we learned about cell communication and how interaction with a receptor would result, or cause a specific occurrence. This connects to luciferase’s binding to its sensor, causing the glow affect. This cell communication also connects to the two CRISPR proteins attaching to a specific nucleid acid sequence. If the nucleid acid holds the viral genome and the luciferase, it would connect and form a glow response – a direct example of intercellular communication. Continually, we learned about DNA manipulation and alteration and how segments can be added in, substituted, or even removed. This occurs in CRISPR gene editing’s nature as a genome editing tool. It exemplifies all these manipulations to both DNA and RNA. We also learned about ideal protein function at a variety of temperatures, pHs, and environmental settings. This idyllic setting in seen in RPA’s function at a continuous 100 F.

To close, I feel that the use of luciferase, or “glow in the dark” proteins fronts an entirely new way of combating diseases and supporting disease identification. It would provide a new way for doctors and scientists to diagnose patients in a time efficient manner. And frankly, the idea of being diagnosed by something “glow in the dark” is entirely lightening and provides some relief to the gravity of the situation. I invite any and all comments regarding this specific method of disease identification or any other relevant discussion points.

Can Your Lungs Work Against COVID-19?

Within the last two to three years there has been an immense focus in the field of science, COVID-19. This pandemic has sparked a myriad of research opportunities as well as brought up questions we didn’t even know we needed answered.

With this, recent research at the University of Sydney shows that our lungs contain a protein that blocks the COVID-19 infection and works to create a protective barrier within our body. The way it works is that a protein receptor found in our lungs sticks to the virus, and then pulls it away from the targeted cells. The protein is known as the Leucine-Rich Repeat-Containing Protein 15 or in short, LRRC15. For context, leucine is an essential amino acid for protein synthesis as well as many other biological functions. The protein is a built-in receptor inside of our bodies that binds to the COVID-19 virus and doesn’t pass on the infection.

Lungs diagram detailed

Initially, the research was published on February 9, 2023, in the PLOS Biology Journal. Led by Professor Greg Neely and his team members, the findings serve to open a new sect of immunology and COVID research, specifically around the protein, LRRC15. Moreover, it creates a path to develop new drugs and treatments to prevent infections such as COVID-19. Greely states that ” This new receptor acts by binding to the virus and sequestering it which reduces infection,” essentially the receptor is able to attach to the virus and “squish” it before it moves to infection. He also pushes the idea that the new receptor can be used to “design broad-acting drugs that can block viral infection or even suppress lung fibrosis.” Continually Dr. Lipin Loo, one of Greely’s team members, mentions, “We think it acts a bit like Velcro, molecular Velcro, in that it sticks to the spike of the virus and then pulls it away from the target cell types,” here he outlines the stickiness of both the receptor and the virus as well as the receptor’s nature to latch onto the virus and “hold” it. In addition, Loo states, “When we stain the lungs of healthy tissue, we don’t see much of LRRC15, but then in COVID-19 lungs, we see much more of the protein,” here he fronts the idea that COVID-19 lungs are far richer in the LRRC15 protein than normal lungs, this may be due to a result of the protein’s ability to immobilize the virus.

To outline COVID-19 infects us by using a spike protein to attach to a specific receptor in our cells. It mainly uses the ACE2 receptor to enter human cells. Moreover, our lung cells have high levels of ACE2 receptors, which is why being infected can often cause severe problems in our lungs. Similar to ACE2, LRRC15 is a receptor for COVID. But, LRRC15 does not support infection, instead, it sticks to the virus and immobilizes it. This prevents other cells from becoming infected. LRRC15 attaches to the spike of the virus and pulls it away from certain target cell types. The LRRC15 protein is widely present throughout our body, it is in the: lungs, skin, tongue, fibroblasts, placenta, and lymph nodes. However, the researchers observe that the lungs “light up” with LRRC15 after infection. They think the new protein is a part of our body’s natural response to combatting the COVID-19 infection. It creates a barrier that separates the virus from our lung cells most susceptible to COVID-19 infection

SARS-COV-2

To connect to our AP Bio Class, we learned about adaptive immunity where we develop an acquired immunity after being exposed to pathogens, a specific response. I see some similarity here in that the LRRC15 protein is specific to immobilizing the COVID-19 infection. Additionally, in our Cell Signalling Chapter, we focused on signal transduction and its stages, reception, transduction, and response. Specifically in the reception stage, we focused on intracellular and transmembrane receptors. I think that LRRC15 would be transmembrane in order for it to efficiently bind to the COVID-19 Spike. With this, however, I would like to see more about the transduction component of the LRRC15 receptor. Lastly in our Enzyme Unit, we learned about how different factors can affect enzymatic activity; heat, pH, and even general surroundings. I wonder which factors work to hinder and work to stimulate the purpose of the LRRC15. I invite any and all comments with additional info relevant to the topics discussed.

Fight or Flight? A stroll down memory lane…

Everyone handles fear differently. Have you ever wondered why some people are fearless, while others are afraid of their own shadows? Fear is a natural human emotion that arises when we feel threatened or harmed. Fear can be rational or irrational. In some cases, like post-traumatic stress disorder (PTSD) or anxiety-related disorders, fear responses can be uncontrolled or exaggerated. Researchers have been trying to figure out what specifically triggers fear and how it turns into a long-term memory. 

Depression - a lonely alcoholic in fear covers his face with his hands

This study from researchers at Linköping University investigated the biological mechanisms that impact fear-related memories in the brain. They used rats and discovered potentially groundbreaking data behind anxiety-related disorders and alcohol dependence. For those of us who need a quick lesson on the brain, the amygdala regulates emotions and is activated by endangerment or threats. The nerve cells connect the frontal lobe to the amygdala. Interestingly, the research found that these connections are changed in people with anxiety-related disorders. 

 

Specifically, they investigated a protein known as PRDM2. This protein encodes a zinc finger protein that can bind to different types of proteins and receptors. Levels of PRDM2 seem to play an important role in exaggerated stress responses and are also lower in those who are alcohol-dependent. It is common for anxiety-related disorders and alcohol dependency to be present at the same time, and the researchers suspect that this is caused by the protein. 

 

A little more review on the science of the brain is needed before we continue.  The formation of memories are complex and may be connected to our fear responses.  Consolidation is when new memories are formed and preserved into long-term memories. Increased activity between the frontal lobes and amygdala increases learned fear reactions. The decrease in PRDM2 increases the consolidation of fear-related memories. 

Mental Health - The Noun Project

The research suggests that patients with anxiety-related disorders may benefit from treatments that weaken fear memories. Researchers have discovered a way to down-regulate PRDM2, but do not have a way of increasing it, yet. This mechanism could be a part of the explanation as to why individuals have a greater susceptibility to anxiety-related disorders and why these disorders are commonly associated with alcohol dependency. 

Protein PRDM2 PDB 2JV0

One thing we have learned thus far in AP Biology class is that ribosomes are protein factories located free in the cytosol or bound to the rough endoplasmic reticulum or nuclear envelope. Within the rough endoplasmic reticulum, proteins are produced to either be secreted outside the cell, membrane-embedded proteins, or proteins to go inside organelles. 

 

Although they have not discovered a way to increase PRDM2, it is very interesting for us to be able to understand how our fear memories turn into long-term memories and what causes individuals to be more vulnerable to mental health disorders. Hopefully, with the continued research on the biological mechanism that may cause fear, we can reverse engineer the cause and create new innovative medicines to treat and, perhaps, completely cure them. 

Are Skittles Toxic from Titanium Dioxide?

 

 

A lawsuit came out in recent months that made claims of the chemical titanium dioxide, a toxin known to scientists being found in a popular candy, Skittles. A consumer filed a suit against Skittles manufacturer, Mars, for titanium dioxide is now a banned chemical according to the European Union. However, in many countries, such as the United States and Canada, titanium dioxide is still considered to be safe to consume. There still needs to be regulations put about the amount of the chemical that can be found in food, but in limited amounts, many think it is relatively harmless in small doses. Toxicologists who are studying the chemical found research indicating that using chemicals. Agnes Oomen, a senior scientist at the Netherlands’ National Institute for Public Health and the Environment, told Scientific American that saying we’re not certain that it’s safe is very different from saying it’s unsafe.” When the European Union placed the ban on titanium dioxide, they were just being overly cautious.

What is Titanium dioxide? It is a white powder that is used as a pigment in many candies and other consumer items, such as makeup and paints. Titanium dioxide is good at scattering visible light. This causes products that contain the chemical a brighter and more vibrant color. What raised skepticism for consumers was the fact that Titanium dioxide is also used in many sunscreens because it is an efficient barrier to ultraviolet light.

The United States Food and Drug Administration had deemed the chemical safe in food, but it still must be a regulated amount of not being able to be more than 1% by weight of the product. In contrast, Europe is going through a period of “great detox”, for the European Food Safety Authority (EFSA), an organization that researches the risks of foods, is banning many chemicals previously found in products. In 2021, EFSA found in a report that titanium dioxide can be genotoxic. That means the drug could alter genetic materials such as DNA. This possibility is what causes the EFSA to ban the use of titanium dioxide in products. Oomen participated in making the report about titanium dioxide saying the decision “is on the cautious side.” The European Union’s decision to ban the chemical was based on a slight possibility that titanium dioxide is harmful, for there has been no evidence so far that proves it could cause people any significant dangers.

Saji George, from McGill University, said researchers are “ missing other big parts of the picture. There are so many other things that could be happening with small, consistent amounts of titanium dioxide in a diet over a long period of time.” Along with his colleagues, they recently discovered that the chemical could amplify allergies to some proteins in foods, making titanium  dioxide still a concern. George also mentioned that the studies done on titanium dioxide were done mainly on rates, not humans. “We don’t know how titanium dioxide could enhance certain diseases—for example, inflammatory bowel disease in people with preexisting conditions,” he states. This just goes to show there is still a lot we don’t know about the drug.

Oomen agrees with the European Union’s decision to ban the use of titanium dioxide because researchers have not made any conclusive findings that confirm if the drug is safe or could be harmful. She feels there needs to be a more suitable method to study the chemical. Norb Kaminski, director of the Institute for Integrative Toxicology at Michigan State University said “I think that titanium dioxide in the amount that it’s used in Skittles and food products is of no toxicological concern or health concern to the public. There’s just not the evidence to support that currently.”

This topic relates to our most recent unit in Biology because one of the concerns regarding titanium dioxide involved the alteration of DNA. We learned about DNA in this unit when we learned about organic compounds. DNA is one of the nucleic acids we learned about when we studied different organic compounds. DNA functions to store all our hereditary information, and it plays an essential role in our cells. Also, that titanium dioxide had the potential to cause allergies to proteins found in certain foods. We learned about protein being another organic compound vital to the cell. We learned about all the different functions of proteins that are crucial for all cells to function properly.

 

Did You Inherit Stress From Your Mother?

Have you ever wondered why you are so stressed? Maybe because of school, sports, or homework, but have you ever thought you could have inherited from your mother? I bet not. Biologists at the University of Iowa found that roundworm mothers subjected to heat stress passed the stress exposure to their offspring and their offspring’s children. 

C elegans maleStress2a

In a study last year researchers looked at how mother roundworms react when she senses danger, such as a change in temperature. Their results were that the mother ringworms release serotonin when she senses dangers by traveling from her nervous system to warn her unfertilized eggs.  The warning is there “stored”, and then passed to offspring. Genes have “memories” of past environmental conditions that affect their expression even after these conditions have changed. It is still unclear how this “memory” is established, how it persists past fertilization and after the embryo develops into adults because most organisms typically reset any changes that have been made to genes’ past activity. 

The research team turned to the roundworm, a creature regularly studied by scientists, for clues. They exposed mother roundworms to unexpected stresses and found the stress memory was ingrained in the mother’s eggs through the actions of a protein called the heat shock transcription factor, or HSF1. The HSF1 protein is present in all plants and animals and is activated by changes in temperature, salinity, and other stressors. Although protein can be found in both Prokaryotic and Eukaryotic cells, this particular protein is only found in Eukaryotic cells which means that it interacts with numerous things found in these types of cells. HSF1 interacts with mRNA processing, chromatin modification, transcriptional coactivators and corepressors, and DNA and RNA metabolism which are all an array of proteins with diverse cellular functions. As we learned in biology, proteins nearly have every task of cellular life, including receiving signals from outside of the cell and mobilizing intracellular response which explains why the HSF1 protein has many functions.

The team found that HSF1 recruits another protein, an enzyme called a histone 3 lysine 9 (H3K9) methyltransferase. This normally acts during embryogenesis to silence genes and erase the memory of their prior activity. However, the research team observed something else entirely. They found that HSF1 collaborates with the mechanisms that normally act to ‘reset’ the memory of gene expression during embryogenesis to, instead, establish this stress memory. One of these newly silenced genes encodes the insulin receptor, which is central to metabolic changes with diabetes in humans, and which, when silenced, alters an animal’s physiology, metabolism, and stress resilience. Because these silencing marks were found in offspring, their stress-response strategy was switched from one that depended on the ability to be highly responsive to stress, to relying instead on mechanisms that decreased stress responsiveness but provided long-term protection from stressful environments.

What the team concluded was that if the mother was exposed to stress for a short period of time, only its offspring would be subjected to stress in utero, but the offspring’s children would not. If the mothers were exposed to stress for a longer period of time, then the offsprings children would retain this “memory” of  stress.

 

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.

 

A New Way to View Pain

Often times when we discuss injuries we have sustained, indelible memories of vivid childhood accidents will rush to the surface of our thoughts perhaps even causing minor physical discomfort in the body part related to the accident. For some of us, when certain graphic images of wounds are shown, we will begin to experience a tingling sensation in those areas of our own bodies. For others, remembering how they broke a bone can seem anticlimactic. So from these observations, the question arises: why do we each remember pain the way that we do? 

In an article regarding mothers’ progressive memory of childbirth, the renowned online mental health resource Psych Central disclosed their groundbreaking research, which suggested a strong correlation between memory of childbirth and how many children these women ultimately had. About 50% of the mothers rated their childbirth as less painful than they did initially. While this data fails to suggest that the majority of women forget the intensity of their labor pains, it shows that a significant amount do. A potential explanation for this habit is that there is a positive correlation between being able to forget the pains of childbirth, and how many children one of the subjects had. This implies that being able to forget specific pains can be useful if the potential gain is more worthwhile than temporary pain. 

However, on the other end of the spectrum, remembering pain can be used to prevent the acquisition of future injuries in the same way. Discovery Magazine released an article about how memories are linked with pain through a protein called PKMzeta. It goes into the synapses between neurons, and strengthens bonds. This creates more connections for vivid memories to arise. The PKMzeta protein forms new connections in the spine after painful experiences, the same way it does when we are forming new memories. Thusly, our pain is a sign of new knowledge.

 

Arthritic Pain

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.

 

 

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.

DNA

Photo Credit: https://commons.wikimedia.org/wiki/File:DNA_com_GGN.jpg

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.

Goodbye Leukemia– We Are Getting Closer!

A new finding suggests that the protein nup98 found in mouse cells may have another job. This is big in the biology world! Scientists already know this protein helps control the movement of molecules in and out of the nucleus, but they didn’t know it is directly involved in the development of blood cells. After further study, scientists from the Salk Institute found that nup98 enables immature blood stem cells to differentiate into mature cell types. However, this was not even the biggest finding– this differentiation process can contribute to the formation of leukemia!

The journey to make this discovery Salk’s Chief Science Office, Martin Hetzer calls, “combined genomics, proteomics, and cell biology.” It was a complex process at the least. It all started with the Hetzer’s lab focusing on a class of proteins called nucleoproteins (nups), part of the nuclear pore complex, which regulates the space between the nucleus of the cell. Why is this space so important? Because it is where the genetic material is located and the cytoplasm contains multiple important structures! There are about 30 of these proteins and some of them even have functions beyond forming the nuclear pore as transcription factors. Thus, the idea that a protein has more than one function (like nup98) was not a total surprise for the researchers (I still would have been surprised).

Although we know that nup98 has plays a role in hematopoietic (blood) cells, we do not know how yet. That is a question of the future. However, “The investigators found that it acts through a link with a protein complex called Wdr82-Set1/COMPASS, which is part of the cell’s epigenetic machinery.” Wait what do those numbers and epigenetic machinery mean? It is basically just a process that controls when genes are transcribed and when genes are blocked (hope that helped). The other big question is how this study will parallel in primates and humans, but the future is bright.

The continuation of this study in regard to Leukemia is now left in the hands of leukemia researchers, but cancers driven by a single genetic change like this have been proven easier to treat with drugs than cancer driven my multiple genetic changes. Although this discovery is only the first of many, there is hope for an even bigger finding in the future! I am excited to see what research is to follow. What about you?

Could A Computer Detect Your Sick Gut?

Photo by Nicola Fawcett (photo source)

 

The human gut microbiome is a system specially revolved around the genetic makeup of an individual person. These gut biomes are the subject of many studies by scientists who are interested in the small world of bacteria living inside of our stomachs and its relation to our health or illness. Many humans have the ability to recognize a healthy or unhealthy human gut microbiome, however, is it possible for a computer to have this same ability? According to the impressive research results developed by a group of scientists at the University of California San Diego, it is possible for a computer to be trained to differentiate a sick gut microbiome compared to an unhealthy one.

In order to reach this innovative conclusion, these scientists utilized metagenomics, a gene sequencing technique, to break up the DNA of hundreds of microbes residing in the human gut. The scientists took gut bacterial samples from the stool samples of thirty “healthy” and thirty “unhealthy” people. The unhealthy people whom had samples taken from them were either diagnosed with autoimmune Inflammatory Bowel Disease. With these 60 samples total, the scientists were able to sequence 600 billion DNA bases and put the information into a computer. After that, the scientists underwent a complex process of translating reconstructed DNA of the hundreds of microbes into thousands of proteins, which were then categorized into thousands of protein families. The tedious differentiation and categorization of certain proteins allows the scientists to see the activity of the bacteria and then program it into the computer so it, too, would be able to recognize these proteins and bacteria. Bryn C. Taylor, One of the scientists involved in this research says that, “You can try to categorize healthy and sick people by looking at their intestinal bacterial composition…but the differences are not always clear. Instead, when we categorize by the bacterial protein family levels, we see a distinct difference between healthy and sick people.” Incorporating this method of distinction with the storage of healthy and unhealthy patient data into computers is an effective way of “training” a computer how to detect a sick or healthy human gut due to a distinguishable difference in bacterial activity, protein presence, etc..

Overall, it seems that these scientists at the University of California San Diego have made groundbreaking progress in the future usage of computers in the detection of an unhealthy or sick human gut microbiome. Do you think the development of a computer’s ability to detect a sick gut will be ultimately more beneficial to the world of health and science, or will it just be an unnecessary new trick that computers can learn? The next time you feel like you’ve got a stomach bug, you just might be scheduling an appointment with a computer instead of your doctor.

https://commons.wikimedia.org/wiki/File:Wild_garden_of_the_gut_bacteria_3.jpg

 

XRN1: The Virus Hitman

When I think of the words killer and assassin, my mind drifts to shady men in all black equipped with sniper rifles. However, recent research conducted by the University of Idaho and the University of Colorado Boulder has indicated that I should expand that mental list to include XRN1, a gene in saccharomyces cerevisiae which, according to a recent study, kills viruses within the yeast. Upon stumbling onto this subject, I was intrigued because it was a fairly simple procedure that led to a huge discovery. To grasp the significance of such a discovery, one must understand it on a molecular level. XRN1’s duty in yeasts is to create a protein which breaks down old RNA. The image below shows the generic process of the creation of a new protein through gene regulation.

Wikipedia- Regulation of Gene Expression

Wikipedia- Regulation of Gene Expression

Yeasts also contain viral RNA since practically all yeasts are infected by viruses. When scientists removed XRN1 from the yeasts, the viruses within yeasts replicated much faster, and when they expressed high amounts of XRN1, the virus was completely eradicated. This is because the XRN1 gene was inadvertently breaking down the viral RNA, mistakenly taking it for the yeast’s RNA. Scientists continued the research by using XRN1 from other saccharomyces yeast species. The virus continued replicating rapidly but the XRN1 did continue its job of breaking down the yeast’s RNA. This shows that the XRN1 from each yeast species evolves to attack the specific viruses that occur in its host while still maintaining their basic role as the RNA eaters. Scientists are hopeful about this study’s human health implications. Viruses such as Polio and Hepatitis C work by degrading XRN1 and not allowing it to break down RNA, respectively. Dengue Fever also occurs when XRN1 is unable to perform its function of RNA breakdown. These studies on Dengue Fever and Hepatitis C elaborate on the implications of XRN1 not breaking down RNA. Scientists hope that this discovery could lead to the triumph of XRN1 over these viruses. Could this really be the discovery that leads to the first ever Hepatitis C vaccine? Do you think that XRN1’s success against virus in yeasts guarantees eventual success against viruses in humans?

 

Original Article: http://phys.org/news/2016-10-yeast-gene-rapidly-evolves-viruses.html

 

Could non-gluten proteins play a role in celiac disease?

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Gluten refers to the proteins found in wheat endosperm. Wheat endosperm is a type of tissue produced in seeds that’s ground to make flour.  It is composed of two different proteins: gliadin (a prolamin protein) and glutenin (a glutelin protein). Today, there are many questions being asked about whether we should be consuming gluten.

In today’s society, one of the new healthy trends is to be gluten free. However, for those with celiac disease, it is necessary to be gluten free. Celiac disease is a condition that damages the lining of the small intestine. It prevents the intestine from absorbing parts of food that are important for staying healthy. In this article, questions are raised regarding research that claims that people with celiac disease also have reactions to non-gluten proteins.

From research, scientists have discovered that when someone with celiac disease eats gluten (group of proteins), it causes an immune reaction. Such symptoms are diarrhea, abdominal pain, anemia, and nutritional deficiencies. The current treatments are to avoid all gluten-containing foods. Armin Alaedini, Susan B. Altenbach, and their colleagues wanted to further investigate this.  They found that people with celiac disease and dermatitis herpetiformis (a rash associated with the disease) had an immune reaction to five groups of non-gluten proteins. From this, Scientists concluded that further studies regarding celiac disease and gluten should test and include non-gluten proteins.

In addition, according to the National Institute of Diabetes and Digestive and Kidney Diseases, the way to test for celiac disease is through a blood test and then a follow up biopsy on the small intestine. When people have celiac disease and it goes untreated, their body is not receiving the necessary nutrients in order for the body to grow.

I chose this article because I try to be extremely conscious of making healthy eating choices. I have found that a lot of foods don’t agree with me but bread/ gluten has never been a concern. I know people who have celiac disease and are gluten-free. However, I also know people who do not have celiac disease and eat a gluten-free diet anyway. In some cases, people who have done this have found that it damages their stomach and ruins their ability to eat gluten. I researched this topic because I wanted to learn the truth behind a gluten-free diet and when that diet is truly necessary and appropriate.

Are you gluten-free? Do you have celiac disease? Have you ever tried gluten-free products?

 

http://celiac.org/celiac-disease/what-is-celiac-disease/

http://www.livescience.com/39726-what-is-gluten.html

http://en.wikipedia.org/wiki/Gluten

http://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/celiac-disease/Pages/ez.aspx

Article Link: http://www.biologynews.net/archives/2014/11/05/could_nongluten_proteins_play_a_role_in_celiac_disease.html

 

 

The Ability to Control Genes with Your Thoughts

A research group led by Martin Fussenegger, a professor of Biotechnology and Bioengineering at the Swiss Federal Institute of Technology, has developed a method by which brainwaves control the creation of proteins from genes. The technology wirelessly transfers brainwaves to a network of genes that allows the human’s thoughts to control the protein synthesis of the genes. The system uses a uses an electroencephalogram (EEG) headset, which records and transmits a human’s brainwaves and sets it to the implant in the gene culture.

A successful experiment of the system included humans controlling gene implants in mice. When activated by brainwaves, the gene implant culture would light up by an installed LED light. The researches used the human protein SEAP as the protein that would be generated in the culture and diffused into the blood stream of the mice. The humans were categorized by their states of mind: “bio-feedback, meditation and concentration”. The concentrating group caused an average release of SEAP. The meditation group released high concentrations of the protein. Finally, the bio-feedback group produced varying degrees of SEAP, as they were able to visually control the production of the protein as they could view the LED light turning on and off during the production process. The LED light emits infrared light, which is neither harmful to human nor mice cells. The system proved successful in its ability to translate brainwaves into gene control and protein production and its potential for harmless integration into the living tissue of humans.

The research group hopes that in the future a thought-controlled implant could help prevent neurological diseases by recognizing certain brainwaves at an early stage of the disease and translating the brainwaves into the production of proteins and other molecules that would work to counteract the disease.

Lights of ideas

Proteins Keeping Fishes Alive

 

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Words To Know:

notothenoids: the arctic ice fish

practical application: how organisms adapt through natural selection

superheating: solid is above its melting point but does not actually it to melt at this point

Origins: 

     Fish in Antarctica have been forced to evolve natural antifreeze proteins to stay alive.  These proteins are mainly found in the notothenoid fishes, which are found in freezing temperatures. Arthur DeVries discovered these fish, their ice- binding-proteins and also figured out how they work in the 1960s . The proteins bind to small crystals and also protect cells by binding to their cell membranes. They are anti-freezing proteins that allow fish to survive and adapt to harsh and cold conditions of arctic waters.

Recent Discoveries:

          Paul Cziko, among other researchers in the United States and New Zealand, published in The Proceedings of the National Academy of Sciences that these ‘anti freeze’ proteins’ are also ‘anti melting’. Cziko and his team wanted to understand the antifreeze ability and examined if an anti-freeze protein (that was attached to an ice crystal inside the fish) would melt when the temperature rose. Instead, they found that the ice crystals did not melt. Ice above the melting is point is considered superheated. Cziko’s research basically says that even when it is way past its melting point, the ice (that’s latched on to the protein) still stays frozen inside the fish. These ‘anti-freezing’ proteins are also ‘anti-melting’ proteins that cause ice crystals to accumulate in the fish’s body.

The study shows evolution, not practical application, and this is a typical case of ‘evolutionary trade off’. There are difficulties that get solved, but there’s also a price to pay. Cziko’s research has not indicated any unfavorable effect due to the crystals, but the crystals could potentially block up the blood vessels of the fish and provoke an inflammatory reaction.

Personal Statement: 

      Personally, I really liked the NY Times article. I actually didn’t realize that we had to find additional articles until I re-read the assignment sheet. I found other articles because I was genuinely curious as to how this worked and came about. I was initially attracted to the word ‘protein’ in the article’ title -since it relates to what we are learning in class- but stayed because of the evolutionary aspect. It has always been hard for me to think of evolution as something. It is such a difficult-to-grasp concept since you can’t really see it happening . But, in some way- this made me think that I did see evolution. Instead of making me think of evolution as a concept or theory that I learn at school, it made me think of it as a reality, and as something that actually happens.     

Original Article: http://www.nytimes.com/2014/09/23/science/antifreeze-proteins-keep-antarctic-fish-alive-and-icy.html?ref=science&_r=0

Additional Article: http://thewestsidestory.net/2014/09/23/17354/antarctic-fish-anti-freeze-anti-melt-proteins-keeps-freezing/

Additional Article: http://www.scienceworldreport.com/articles/17326/20140923/antarctic-fish-antifreeze-blood-ice-crystals-bodies.htm

Study Shows Link Between Enzyme and Spread of Breast Cancer

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 “40,000 women in America will die of breast cancer in 2014.” This is a truly terrifying projection. Breast Cancer is an extremely deadly, and extremely prevalent cancer that affects the lives of millions each year. In my personal experience, I have many friends and family members that have battled against this cancer. So many are affected, and there is still no concrete cure. There is no cure, however, researchers at the University of California, San Diego School of Medicine have identified an enzyme that is closely related to the metastasis of breast cancer cells. This is great news, for it suggests the possibility of further research using this finding to end breast cancer for good. Xuefeng Wu, a lead scientist involved with this research, has stated that the team has been able to “target breast cancer metastasis through a pathway regulated by an enzyme“. This enzyme is called UBC13 and it regulates the activity of a protein called p38.

This p38 protein, when not in use, prevents metastasis. By identifying the enzyme that prevents the use of p38, researchers have come one step closer to preventing the spread of breast cancer in the body, and therefore defeating it. With the use of a lentivirus injected into the mammary tissues of mice, the scientists were able to suppress the functions of both UBC13 and protein p38. The mice grew primary tumors, as was expected, however the primary tumors did not metastasize and spread breast cancer cells throughout the bodies, which means the cancer was stopped from spreading throughout the body. This prohibition of the cancer cells to spread is a major breakthrough in breast cancer research and will without a doubt contribute greatly to the ending of breast cancer.

Protein Structure May Lead to Cure for Ebola

For those who haven’t been keeping up with the latest in viral outbreaks, Ebola has been spreading throughout West Africa and has already taken the lives of 2,600 people since the outbreak in March 2014.  According to the World Health Organization , there are currently no certified vaccines or treatments for Ebola but a new breakthrough may have answers to developing a cure or vaccine for the deadly disease

Scientists at the University of Virginia have gotten their hands on a crystalized structure of the Ebola Nucleoprotein C-Terminal domain, which is an important protein used in replicating the virus.  The tertiary fold of the C-terminal is “unique in the RNA virus world,” claims structural biologist Dr. Zygmunt Derewenda, and this unique fold could ultimately lead to the foundation of drugs to prevent further infections.

The team was able to produce the protein by using E Coli as the protein factory.  So far, the protein demonstrates traits that are extremely unique and unlike other known proteins.  Evidence thus far has shown that the viral nucleoapsid is self assembled by the domain.  Insights and new research that the UVA team is conducting is paving the way to an Ebola anti-viral drug.

 

Ebola Virus Particles

 

Protein Might Help Fight Deadly Diseases

The enzyme “Cholesterol-25-Hydroxylase,” or CH25H, might help fight against human viruses such as Rift Valley Fever, Niphah and HIV. CH25H converts cholesterol to an oxysterol called 25HC, which can permeate a cell’s wall to prevent a virus from getting in. The CH25H enzyme is activated by interferon, an anti-viral cell signaling protein produced in the body.  Researchers have known that interferon has been part of the body’s defense mechanism against viruses, though it does not have any antiviral properties itself.

This discovery is revolutionary because other antiviral genes have not been able to be used for treatment of viruses in humans. According to Yang Lui, a student at the David Geffen School of Medicine at UCLA, most antiviral genes are difficult to use in therapy because the genes are difficult for cells to express. However, CH25H is different because it is naturally synthesized.

HIV Replication within a cell

The discovery of CH25H is relevant to the efforts to develop broad antivirals against an increase of emerging pathogens. In a collaboration with Dr. Lee, another UCLA professor, it was discovered that the 25HC produced from CH25H can inhibit HIV growth in vivo. The researchers initially found that 25HC inhibited HIV growth in cultures. When implanted mice with human tissues, the 25HC reduced the HIV in within 7 days and reversed T-Cell depletion caused by the HIV. It was also discovered that 25HC inhibited the growth of other diseases such as Rift Valley Fever Virus and Ebola.

There are still some weaknesses with the study. It’s difficult to deliver 25HC in the large doses needed to fight viruses. Researchers also need to compare 25HC to other antiviral HIV treatments.

Fighting Cancer with Protein P53

Despite the amazing diagnostic technologies, pharmaceuticals, and procedures of modern medecine, cancer still takes the lives of more than half a million people in the US every year. Characterized by the unmediated reproduction and metastasis of tumorous cells, the various forms of the disease have proved difficult to slow and often nearly impossible to cure. Treating cancer usually requires rigorous chemotherapy or invasive surgery, each involving painful side-affects and long recovery periods.

Chemotherapy, while effective, indiscriminately attacks cells that divide quickly. Thus, the fast-dividing cells lining the mouth and intestine as well as the cells that cause hair to grow are also affected, causing an array of side affects. Scientists have been searching for a new way to fight cancer that would only target cancer cells while letting healthy cells function unhindered. A team at University of California, Irvine may have found that method in protein P53, mutated forms of which are implicated in “nearly 40 percent of diagnosed cases of cancer.

P53 is responsible for repairing damaged DNA and causing apoptosis, or programmed cell death, in cells that are damaged beyond repair. In a mutated form, P53 does not function properly, allowing cancerous cells that would normally be destroyed to proliferate. A therapy that reactivated mutated proteins could potentially surpress tumors without causing the nasty side affects of current drugs. Also, since P53 is present in so many cancer cases, a single treatment could be used against many different forms of the affliction. However, since P53 proteins “undulate constantly, much like a seaweed bed in the ocean,” sites where medicinal compounds could bind are difficult to locate.

The UCI team had to reach across disciplinal boundaries, enlisting computer scientists, molecular biologist and others to find a usable binding site. With the help of molecular dynamics, the group constructed a simulation of P53’s movements, eventually locating a transient site that could bind with stictic acid, one of forty-five small molecules they tried. Unfortunately, stictic acid is not a viable compound for pharmaceuticals, but the scientists at UCI think that other small molecules with similar characteristics will likely have similar effects and make effective treatments.

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