BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: proteins (Page 1 of 2)

Is the recently discovered hidden cavity on the SARS-CoV-2 protein a target for drugs?

Many of us have been vaccinated against COVID-19 and have had the virus, leading us to become used to the virus being prevalent in our lives during the past few years. Even though a successful vaccine has been rolling out for a while now, new therapies have not yet been discovered for future strains. Finding new therapies for the virus remains a major priority in the field of science, even if many of us have been protected already. This issue remains a priority because new variants and strains have been continuing to emerge, and some resist present therapy mechanisms.

SARS-CoV-2

The most effective approach to attempting to combat the virus is addressing the proteins on the surface of therapeutic targets, known as spike proteins. The spike protein (S proteins) located on the surface of the virus leads to its spiky protrusions, and its mechanism to enter human cells. Like we learned in AP Biology class, the spike proteins of the virus latch to cells by matching with a specific receptor on a cell’s surface. The spike proteins of the virus have to latch on to the new cell to infect. Successful messenger RNA vaccines properly target this spike protein, which is the main goal when creating new therapies for viruses. 

                                             Spiky appearance of SARS CoV-2 virus

Luigi Gervasio, a chemistry and structural/molecular biology professor at University College London, and his team have been working towards addressing this issue. By partnering with the University of Barcelona’s research team, the two teams took the first steps to discover a possible mechanism for future drugs to detect and protect against the SARS CoV-2 Virus. Through thorough research and investigation, they uncovered a “hidden” cavity on the surface of a prominent infectious agent of the virus known as Nsp1. The team was able to make this discovery by testing small molecules that had the potential to bind to the Nsp1 cavity. The team identified one, 5 acetylaminoindane, which is essential for the development of new drugs against viruses. They concluded that this cavity permitted the calculation of the cavity’s atomically spatial arrangement, which will allow the development of these drugs.

The results of their breakthrough findings set the stage for developing new therapies that will be able to target the NSp1 protein against SARS-CoV-2 and present Nsp1 proteins in future coronavirus strains. Not only will this finding be impactful for targeting SARS-CoV-2 and future variants, but also new cavities on the surface of other proteins that have yet to be found by scientists. Finally, this research is monumental for both SARS-CoV-2 and virus treatment in years to come!  

 

Can this Protein Cause Alzheimer’s?

What causes Alzheimer’s? Initially, one might think that it is a result of age-related changes in the brain or environmental and lifestyle changes. One may also think that it is caused by a genetic predisposition to the disease. Personally, I thought Alzheimer’s was a result of poor health as one got older. Although these all may be true, a new study has found that Alzheimer’s Disease can be caused by a certain protein, or rather, a protein mutation. These new findings provide scientists with a way to detect and treat the disease in the long run.  Using multiple methods to analyze mitochondrial DNA, researchers found a mitochondria microprotein that is associated with Alzheimer’s Disease. This protein, known as SHMOOSE is seen to have a role in the neurodegeneration of people, thus giving them an increased chance of Alzheimer’s Disease. Furthermore, the researchers found that the microprotein is found in over a quarter of Europeans. The researchers of The Cohen Laboratory at the University of Southern California published their findings in the journal of Molecular Psychiatry. The journal states that the microprotein, SHMOOSE was discovered through the use of neuroimaging, mass spectrometry, and transcriptomic. All of these are methods of looking into the mitochondrial DNA and locating the mutated protein. According to the study, a mutation of the SHMOOSE microprotein has a connection to a higher risk for Alzheimer’s Disease. They also discovered that 25% of individuals with European ancestry have the mutated version of the protein. Dr. Pinchas Cohen says that the SHMOOSE mutation is a result of a single nucleotide polymorphism or SNP. An SNP is essentially a change or alteration within a single nucleotide, in this case, the change resulted in the mutated SHMOOSE protein. Additionally, he states that the variant can guide ways to identify who is affected while also forming new medical treatments and preventative measures. In class, we learned about how proteins are created and coded for, and we also learned about how protein structure directly affects their function. Both of these concepts are directly seen in this study. Firstly, DNA is what codes for proteins, if the DNA or even the nucleotide is incorrect or altered, the protein would in turn also be incorrect or altered. This is seen directly through the SNP, the single change in the nucleotide entirely changed the protein creating the SHMOOSE protein. Next, the structure of the protein, the sequence of the amino acids, or just the overall composition of the protein entirely plays a role in the function and actions of the protein. For example, if the structure of a protein is compromised, so is the function. This is also directly seen in the study because the structure of the SHMOOSE protein was altered due to the SNP, its function was also altered. The altered function is that it would put people at a higher risk for Alzheimer’s Disease. Another article speaks on the silver lining of the SHMOOSE protein. Because the protein is the approximate size of an insulin peptide, it could easily be administered into the human body for a positive effect. This means that the mutated protein could be used for treating Alzheimer’s Disease and increasing its therapeutic value. This idea is just one of many that venture into the field of precision-based medicine. In the case of Alzheimer’s the mutated SHMOOSE would be focused upon as a target area rather than the disease as a whole. I think that the use of SHMOOSE in a medical or therapeutic way would be risky at first in that it would likely be difficult for scientists to specifically target the way to treat it. What may be a safer option for those with the mutation could be to continue with tried and tested Alzheimer’s Disease treatments rather than immediately opting for something new. The new precision-based medicine method should undergo severe trials, examinations, and successes before it is widely implemented.

 

Noun Alzheimer Nithinan 2452316

 

Can Reactive Oxygen Species Maintain Stem Cell Function and Prevent Inflammation?

Have you ever wondered what “gut health” really means? What keeps your gut microbiome functioning properly, maintaining homeostasis, and preventing inflammation? Originating from oxygen, reactive oxygen species (ROS) that are highly reactive function as central indicators of cellular flaws and issues in the body, such as inflammation. Nai-Yun Hsu of Mount Sinai has stated that “Reactive oxygen species released by stem cells are critical in maintaining a heathy gut via maintaining proper balance of intestine barrier cell types.”

File:Inflammatory Bowel Disease MTK.jpg 

A team of researchers from the Ichan School of Medicine at Mount Sinai have gone in depth about the importance of these oxygen species for stem cell function, avoiding inflammation, and repairing wounds in a recent study. Using mice as models, the researchers were also able to conclude that microfold cells, called “m cells” regulate an organism’s gut immune response, and emerged from a loss of ROS in mice and humans. 

 

The experiment was conducted in vino and in vitro conditions with the mice cells, and ex vivo conditions with human intestinal biopsies post-colonoscopy. Both the human intestinal biopsies and mouse cells were utilized to determine the amount of ROS in the body to support a finding. In addition to determining the amount of the oxygen species, the biopsies and mice were used to analyze the “gene expression profile” of barrier cells in intestines of mice and humans that are diagnosed with a “subtype of IBD known as ulcerative colitis.”  

 

A decrease in these oxygen species can lead to TNF’s emergence in the body, which is a substance that attempts to maintain homeostasis in the body and avoid inflammatory diseases, like IBD and ulcerative colitis. They have concluded that losing species like NOX1, a protein that creates these species, is directly linked with inflammatory diseases like Inflammatory Bowel Disease (IBD). Judy H. Cho, MD, has stated that the study is a breakthrough “in defining the key role of oxygen species in maintaining a healthy epithelial barrier for IBD.” These reactive oxygen species are relevant to AP Bio considering the information we have learned about general biological systems and cells, which function to maintain homeostasis in the body. The mitochondria, which is an organelle of the cell covered in AP Bio, receives signals from gut bacteria that reveals inflammation. While the mitochondria is typically known as the site of cell respiration and performing reactions, new evidence has shown a relationship between the gut microbiota and mitochondria to trigger immune responses and activate barrier cell function. These processes relate to changes to the mitochondria that occur from gut-related issues in IBD patients, meaning that there is a connection to ROS. 

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Gut Microbiota

As a conclusion to proving the direct link between the highly reactive oxygen species and treating inflammation, these researchers encourage and plan to conduct further study on this topic, but for using “oxygen species-stem cell modulation therapy” to potentially treat IBD patients. 

 

 

Could These Blood Proteins Be The Key To Extending Human Lifespan?

All around the world, companies profit off of the idea of “anti-aging” products; but could these various serums, skincare products, and supplements even have an impact? A study from the University of Edinburgh, in which researchers analyzed six different genetic studies surrounding human aging, suggests otherwise. Instead, after analyzing 857 proteins from genetic information from hundreds of thousands of people, scientists have reason to believe that two distinct blood proteins have negative effects on aging. As we know from AP Bio, different individuals naturally have higher or lower levels of certain proteins depending on their genetics, and the DNA they inherit from their parents. Additionally, we know that each parent provides 23 chromosomes, which encode the same genes, totaling to 46. This means that if your parent has high levels of specific proteins, you have a significant chance of inheriting that.

Ácido desoxirribonucleico (DNA)

 In the case of these two blood proteins, LPA and VCAM1, people who inherited DNA that causes raised levels of these proteins were overall much more weak, unhealthy, and less likely to live a long life. Lipoprotein (a), a lipoprotein variant containing a protein called Apolipoprotein (a), is made in the liver. High levels of this protein are associated with a vast increase in the risk of atherosclerosis, which is a cardiovascular disease in which there is a​​ thickening or hardening of the arteries caused by a buildup of fatty substances in the inner lining of the arteries. Additionally, LPA is also linked to coronary heart disease and strokes. The second protein, vascular cell adhesion protein 1, or VCAM1,  is a protein found mainly on endothelial cells lining the blood vessels. It primarily controls blood vessel expansion and retraction. Elevated levels of VCAM1 are associated with long-term risk of heart failure.

Currently, there are clinical trials working to reduce the risk of heart disease through testing a drug to lower LPA. While there are no trials surrounding VCAM1 at the moment, there has been some animal testing done on mice to see the effects of lowering this protein. In these tests, researchers found that antibodies lowering VCAM1 levels improved cognition in old age for the mice.

The scientific progress and research regarding these two blood proteins is profoundly important, for it has revealed two key targets for future drugs to extend the lifespan of humans who aren’t genetically blessed. It is medical progress and news like this that continuously help us remain hopeful as we, and our loved ones, age.

Protein Responsible for Increasing the Severity of COVID-19

The CDC reported that the first human COVID-19 case, originating in Wuhan, China, to enter the United States was on January 20th, 2020 via DNA samples. Present-day, COVID-19 has affected nearly three hundred million people worldwide according to the New York Times. Now, one would assume that this virus would have the same effects from person to person, yet it actually produces drastically different effects depending on the victim’s body composition. Some people “develop mild or no symptoms upon infection,” whereas others, “develop severe, life-threatening disease” (University Of Kent). But what exactly causes this alteration of symptoms from patient to patient? Well, researchers at the University of Kent have scrutinized through their resources to determine a possible source for this predominant world health issue.

Protein CD47 PDB 2JJS

As we’ve learned throughout units two and three, protein structure is pivotal for determining the protein’s function, and proteins as a whole are what viruses, for example, SARS-CoV-2, consist of on the molecular level. SARS-CoV-2 transmits itself through our body by binding its spike proteins to our healthy cell’s receptors, which then emits a signal to the cell, ultimately altering the genetic code of the cell, changing its function. One protein synthesized from our cells is called ‘CD47,’ a cellular surface protein, which, in broad terms, “tells circulating immune cells called macrophages not to eat these cells” (Stanford.edu).  Once SARS-CoV-2 cells begin to synthesize this surface protein, the cells become ‘protected’ from our immune system, enabling the cells to continuously reproduce and flood the body without any interference from the macrophage and other immune system anti-virus functions. Virus-synthesized CD47 on the surface of SARS-CoV-2 cells allows for the production of higher volume of virus, ultimately resulting in a more severe disease infection.

Viruses-08-00106-g001According to the researchers at the University of Kent, CD47 is far more prevalent among older people, which may provide a reasonable explanation as to why they typically exhibit severer symptoms compared to those of younger people. One condition that high levels of CD47 typically produce is high blood pressure, which forces the body to deviate by over 1o mm Hg systolic and 10 mm Hg diastolic, according to the American Heart Association. High blood pressure, specifically caused by CD47, puts people ” [at] a large risk factor for COVID-19 complications such as heart attack, stroke, and kidney disease”(University of Kent). The researcher’s data demonstrates that both age and virus-synthesized CD47 greatly contributes to more severe COVID-19 by blocking a fully functioning immune response which increases tissue and organ damage.

COVID-19 vaccines (2021) AThis finding should provoke optimism within the scientific community, understanding what causes differing symptoms-severe or less severe- is incredibly useful for combatting both the virus’s spread and severity from person to person. Hopefully, scientists will be able to further utilize CD47 research to save lives of people who are at higher risk of experiencing more severe COVID-19 symptoms.

 

 

Smoking Can Harm More Than Just Your Lungs

When you think of the damage smoking does to your body, you think of your lungs, right? Well, did you know that smoking can actually harm your eyes?

Tobacco has previously been proven to be linked to many leading causes of blindness and vision impairments such as cataracts, glaucoma, and macular degeneration, but all of these effects occur in the inner part of the eye. A new study shows that smoking can actually harm and kill cells on the surface of your eyes.

Research from a recent study conducted by Wataru Otus, a biomedical researcher at the Gifu Pharmaceutical University in Japan, and his colleagues, published by Scientific Reports, found that the compounds found in the smoke of cigarettes and smoking devices cause an iron buildup in the corneal epithelium (the outer layer of corneal tissue on the eye), which can harm and kill cells.

In the study, the researchers exposed human epithelium cells to smoke extract of a cigarette as well as that of heated tobacco devices, and recorded their observations. The researchers found that after 24 hours, more cells that were exposed to cigarette and heated tobacco smoke were killed than those not exposed. They also found that smoking tobacco or using heated tobacco devices caused damage to the cells of the outer eye regardless of nicotine or tar being involved.

The cells that were exposed to tobacco products had damaged cell membranes, lumps of iron, and a lot of damaged ferritin, which strongly indicated ferroptosis, a form of programmed cell death.

Ferroptosis human prostate cancer modelFerroptosis occurred when the compounds in the tobacco made contact with the cells on the outer layer of the eye. The compounds caused the ferritin proteins inside the cells – which store and release iron – to break down and release the iron they were storing. Some of the iron that was released bunched up and produced hydroxyl radicals. Hydroxyl radicals are known to be a very reactive species that attacks organic molecules by removing or deteriorating them. In this case, the hydroxyl radicals attacked the lipids in the film on the surface of that eye, an event called lipid peroxidation. When these lipids are attacked and/or destroyed, your eye is much more likely to dry out, because lipids help prevent the eye from drying out due to their role as lubricators. This is why smokers tend to suffer from dry eye syndromeWhen too many radicals accumulate and are damaging the lipids in the cell membranes, cells can die. The death of eye cells (aka photoreceptors) can lead to the loss of or impaired vision.

As a solution in the study, the researchers found that by adding chemicals that are known to block ferroptosis to the human epithelium cells, more cells exposed to tobacco were able to live, suggesting that ferroptosis treatment could help smokers suffering from eye problems.

Moreover, ophthalmologist Dilek Altinörs of the Başkent University in Turkey, who has studied the results of this study, also suggested that smokers experiencing eye problems should use tear drops with ferroptosis blocking compounds. Although, further study needs to be done on the effects and successfulness of this treatment method. 

The findings of the study help one understand how and why it is that cigarette and tobacco devices affect the eyes of smokers, and show treatments for ferroptosis as a possible treatment for smokers’ having eye troubles. But the obviously best way to prevent smoking from harming your eyes is to not smoke at all. Having smokers learn and understand this new information will hopefully show them yet another reason why smoking is harmful, and why it is in their best interest to quit. 

Progress Towards Solving a 50-year-old Problem in Biology

Protein structures revealed at record pace

One of the hardest problems in biology is predicting the structure of a protein. Proteins are complicated. There are many interactions  between both the side chains and backbones of the proteins, making it very difficult to predict how a protein will fold into its 3D structure solely based on the amino acid sequence (primary structure). In our AP Biology class, we talked extensively about how this 3D (tertiary) structure of the protein is extremely important as it determines the function of the protein. For example, the success of the delta variant of SARS-CoV-2 is largely due to the change in the tertiary structure of it’s spike proteins. Thus, if the 3D structure of a protein is known, it is much easier to predict the function of that protein, and how well it performs the function. However, the methods of determining the tertiary structure of proteins is extremely costly. To determine the structure of a single protein, it can take up to $120,000 and one year.

AlphaFold 2.0 is a breakthrough in this long thought impossible problem. AlphaFold, created by Deepmind, uses deep learning to predict protein’s tertiary structures. In particular, it uses an architecture of transformers, a relatively new and increasingly popular deep learning technique. Using this method AlphaFold is able to achieve remarkably accurate and detailed results, even on an atomic level.

Because of its ability to predict the structure of unknown proteins, AlphaFold can be used to determine how a single nucleotide mutation can affect the structure of a protein. Interestingly, many diseases result from an improperly folded protein, these include: Cystic Fibrosis, Alzheimer’s, and Parkinson’s. While the protein structures themselves do not often lead to the creation of new treatments, they do offer a better understanding of how the protein works. This deeper understanding can then be used to develop new therapies. Thus, AlphaFold has the potential to accelerate new treatments for many untreatable diseases at a much lower cost.

In addition to diseases resulting from misfolded proteins, AlphaFold can be used to predict the effect mutations will have on the folding of the SARS-CoV-2 spike proteins. This can help to quickly determine how a mutation will change the shape (and thus function) of the spike proteins. This makes it much easier to predict how these mutations will affect the spread and severity of the new variants and, using this info, classify the new variants.

However, AlphaFold is not perfect. While most predictions are quite good, a small percentage of the protein structures generated are clearly  inaccurate, putting hydrophobic amino acids on the outside of the protein. Knowing this, it is still necessary to analyze any prediction made by the computational model before using it for biological analysis.  Nonetheless, AlphaFold is a powerful tool for prediction of protein structure and will revolutionize the field of computational protein structure prediction.

If you want to experiment yourself with AlphaFold, a working notebook can be found here. Any PDB sequence can be queried, and the AlphaFold model will predict the structure to the best of its ability.

 

 

Muscle Regeneration: More Than Just “Tearing Muscle Fibers”

Have you ever felt sore after a workout? Maybe your muscles ache and you wonder why this is so? This soreness you are feeling is the result of the tearing of muscles fibers in your body. But the muscle repairing process isn’t as simple as “rebuilding muscles fibers.” It is a part of a chain of reactions and processes that our body triggers in perhaps the most fantastic biological response.

After an intense workout, your muscles are covered in microscopic tears. The easiest and most simple explanation for muscle growth is when you tear these fibers, they grow back stronger leading to stronger muscles. However, a newer study found the presence of scars surrounding the torn muscle fibers. I was totally shocked to learn that after we workout, we get mini scars on our muscles and not just fiber tears. As it turns out, bunches of nuclei go to the scars and begin to heal them. They trigger the release of mRNA which reads the DNA to make new proteins. Who knew that nuclei had something to do with the regeneration of muscles. However, the process of re building a torn muscle fiber is much more extensive than nuclei creating new proteins.

When we dive deeper we can see that there are many different levels to this process. The primary area of rupture after a workout are to the skeletal muscles. Skeletal muscles are laid out in sheets and are connected to bones by tendons. This type of muscle is responsible for a process called protein synthesis. When your body is undergoing an exercise, your muscles are constantly fed protein in order for the cells within your muscles to continue functioning properly and at a proper pace. When your workout concludes, it is vital to consume protein since protein stimulates and accelerates muscle repair and growth. For example, I consume a protein filled meal generally very soon after I workout, making sure I am getting the proper nutrients I need to help my muscles strengthen and prosper. The process of protein synthesis is imperative to muscle recovery and stamina, but if we look even closer into the recovery process we can see a couple of cellular organelles performing some impressive things.

According to the new study, two of the most important organelles in animal cells that is necessary for muscle regeneration is the mitochondria and the nuclei. The mitochondria’s function within a cell is to perform cellular respiration. Cellular respiration is the process where sugars are broken up into useful energy that can be used by the cell and eventually by the body. As we learned in biology class, the mitochondria ultimately converts the sugar glucose into ATP (Adenosine Triphosphate). ATP is essential for muscle regeneration post workout and during a workout because it is responsible for muscle contraction and movement. Just recently, we have learned that the nuclei also comes to the rescue for torn muscle fibers. Nuclei will arrive at the tear and then increase production for more myofilaments, the basis of myofibers. Traditionally, myofibers are the building blocks for muscle growth and rejuvenation. These myofilaments are consisted of small proteins that stimulate muscle movements. All in all, the addition of nuclei to the muscle rejuvenation process highlights the amount of energy needed by the body to perform these functions, which comes from the mitochondria and ATP.

Within the skeletal muscles are areas of high activity that consist of two main organelles doing most of the work: nuclei and mitochondria. The traditional forms of muscle rejuvenation with the mitochondria go hand in hand with the newest discovery of nuclei. In order for the muscle to rebuild it needs proteins and ATP. With the help of these two organelles, this accelerated process can successfully go through. The next time you get sore after a workout, take a second and admire that your body is hard at work with a task that is nothing short of mesmerizing.

Muscle Tissue Skeletal Muscle Fibers (41241952644)

How a Rogue Protein can cause Alzheimer’s Disease

In a study done by NYU Langone Healthy and the School of Medicine, researchers learned more about the types of proteins that cause the tangles in the brain that cause Alzheimer’s. Alzheimer’s disease is a type of dementia that affects the “memory, thinking, and behavior” of the over 5 million Americans who have it, according the the Alzheimer’s Association. The researchers tested tissue sample of 12 subjects with the disease looking for tau knots to “[examine] the bundles to identify the many proteins tangled within”.

File:Histopathology of neurofibrillary tangles in Alzheimer's disease.jpg

Shown is the tangles that are found in and contribute to Alzheimer’s disease 

You might be wondering, what is a tau knot? A tau is a protein that exists mostly in nerves that has the objective of stabilizing microtubules. When this protein is defective, it can become tangled with other molecules which leaders to Alzheimer’s disease.

Although neuroscientists already knew that tau tangles can cause neurodegenerative diseases like Alzheimer’s or dementia, they did not know many of the proteins that cause these dangerous knots. After analyzing the brain tissue, the researchers “found 12 proteins that they say have not before been tied to both tau and Alzheimer’s disease.” These knots were made up of 542 different proteins including those involved in the most essential processes of the cell like “energy production”, “the reading of genetic material”, “and cell breakdown and digestion.” These proteins that work to produce ATP and RNA in the processes of cell respiration and gene transcription (which are necessary parts of cell function); these important proteins are involved in the knotting. It is crazy that along with their existence comes the possibility of them destroying all they have created.

Despite the sad nature of this research, this new information comes along with hope for those suffering from this debilitating illness. According to co-lead author Geoffrey Pires, “Now that we have better insight into possible ‘key players’ in neurodegeneration, we may have clearer targets for potential therapies.” As these researchers gain more and more information, they gain a better understanding of Alzheimer’s and in turn, other similar “tau-linked neurodegenerative diseases, such as Pick’s disease.”

I feel Alzheimer’s is an essential disease to learn more about not only because it is incurable and unpreventable, but because 4 members of my own family have suffered from it. As the study’s senior author Thomas Wisniewski said “Alzheimer’s has been studied for over a century, so it is eye opening that we are still uncovering dozens of proteins that we had no idea are associated with the disease.” It is wild to think that something so common and well known, still has so many mysteries to it and that makes it immensely more fascinating and important to learn about.

A Friendzyme of the Environment

A team of researchers at the University of Portsmouth in England have engineered an enzyme that breaks down plastic six times faster than the previous most efficient plastic destroying enzyme. This enzyme specializes in breaking down PET, polyethylene terephthalate, the material most plastic bottles are made of. They created this by reengineering the previous enzyme, PETase, and combining it with another enzyme, MHETase, to create a ‘super enzyme’. They used a method normally utilized by companies in the biofuel industry, who combine enzymes to break down types of cellulase. Granted, it is still far too slow to be effective in breaking down the vast amounts of plastic waste we are faced with, but it is certainly a step in the right direction.

Enzymes are made of proteins which are made up of amino acids. Amino acids consist of a carboxyl group, an amino group, and a unique R group. Amino acids create chains in which carboxyl group match with amino groups, linking together using covalent peptide bonds, formed after dehydration synthesis. The chains of amino acids begin to fold and create proteins, which are the basis of almost all enzymes.

I think this issue is an important endeavor that should be funded by governments all around the world. We all share the Earth, and it is currently under threat by a number of issues, a prime example being pollution. Up to 8.8 million metric tons of plastic waste may enter the oceans every year. Some studies put the amount of seabirds that contain some form of plastic waste in their system at upwards of 90%. Plastic waste needs solutions before it makes the oceans uninhabitable for more creatures, and a mass produced enzyme may be a valid solution. The Great Pacific Garbage Patch is a large convergence of currents in the Pacific Ocean that has collected so much garbage, a large portion of which is made of plastic, that it is comparable to the size of Texas. Developing an effective enzyme that could quickly break down plastic could become a serious help to minimizing the environmental impact of the Garbage Patch.

While we cannot develop enzymes ourselves, several tips for mitigating our plastic waste are:

-Try to use aluminum cans instead of plastic bottles.

-Always recycle or reuse plastic bottles.

-Cut the holes of six pack rings before disposing so animals cannot be caught in them.

-Use metal and paper straws as a substitute for plastic straws.

 

File:PETase active site.png - Wikimedia Commons

^ The enzyme PETase 

 

 

 

 

 

 

 

 

 

 

 

 

 

Some People Can’t Smell Stinky Fish?!

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

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

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

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

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

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

 

Does This Protein Trigger Alzheimer’s Disease?

Research done by scientists at the Instituto de Neurociencias de Alicante, in Spain has revealed that the way people with Alzheimer’s process a key protein may lead to the creation of new tests and maybe even treatments. Alzheimer’s disease is a common form of dementia, where memory and thinking skills are progressively lost.

People with Alzheimers have a build up of insoluble plaques made of beta-amyloid and tau, both are proteins. Beta-amyloid is a part of a much larger protein called amyloid precursor protein, which is otherwise known as APP. APP is broken down by enzymes into either a beta-amyloid fragment, which is harmful, and causes Alzheimers, or another harmless fragment.

The process of the beta-amyloids forming insoluble plaques.

Glycosylation is the process of adding sugars to proteins, to form a glycoprotein, during production and the location of these sugar molecules is important in determining the ultimate destination of the protein in the cell. The glycosylation of the amyloid is altered in the brain of an Alzheimer’s patient, research suggests. Therefore, the protein is being processed in such a way where more beta-amyloid is being produced. This mutation no matter how small, can play a huge role in how the protein functions. Proteins have a unique shape determined by the interactions of their side chains. The shape the protein forms usually has to match with another molecule or structure. If the structure is mutated in any way, the protein may not remain the same shape and therefore not match the shape of another molecule or structure. This causes a change in the function. Therefore in this case with amyloid, how the protein is glycosylated will determine where it ends up in the cell membrane, due to shape and this will determine if an enzyme will break it down or not. 

The research found a difference between Alzheimer and non-alzheimer patients in terms of how APP is glycosylated. The patterns of APP glycosylation were evidently different. The patterns of proteins are so crucial to their function and structure. So, researchers were able to perform a chemical analysis and found that these different patterns may be a result of different processing of the protein. By processing APP differently, it may trigger Alzheimers. The protein structure is changed and the protein will not act the same. Therefore, with this knowledge, by looking for APP that has an altered way of being glycosylated, it may be easier to detect Alzheimers and inspire treatments in the future. This research is so exciting and important because one day it can help with Alzheimer’s treatments. Not only will it be a great detection test, but the by preventing the creation of beta-amyloid Alzheimers may be preventable in the future or easier to spot. Do you think this sounds like a promising next step to Alzheimer’s detection and treatment?

Trade Your Treadmill for… a Protein?

As humans, we have recognized that regular exercise has many benefits for everyday life. It helps our physique, our muscle and bone health, and it also is responsible for the release of endorphins that improve our mood. However, exercise is time consuming, and some of us just lack the motivation for regular physical exertion.  Scientists at Michigan Medicine have been researching the protein Sestrin in mice and flies, and they have found that “it can mimic many of exercise’s effects,” potentially creating a way to gain the benefits of exercise without actual exertion.

In their experiment, the Michigan scientists used two groups of flies. One group of flies was deprived os Sestrin, while the other group’s Sestrin levels were enhanced. When put through an extended period of exercise, the flies that lack Sestrin did not have any of the typical muscle development and endurance that comes from working out. The flies that received amplified amounts of Sestrin also didn’t progress. However, the Sestrin-boosted flies didn’t receive the benefits of exercise from exertion, because they had already acquired those benefits  from their increased Sestrin levels. In performing the same experiment with mice, “Mice without Sestrin lacked the improved aerobic capacity, improved respiration and fat burning typically associated with exercise.” According to the nature.com article “Sestrins are evolutionary conserved mediators of exercise benefits,” “in vertebrates, endurance training leads to increased mitochondrial biogenesis/efficiency, decreased triglyceride storage, improved insulin sensitivity, and protection of both muscle and neural functions.” Basically, if Sestrin indeed proves to be the magic exercise replacement, it could help alleviate some of the negative physical consequences of aging.

However, our scientists have 2 main problems in turning Sestrin to a mass produced supplement: it’s a very large molecule, and we are still unsure of how the body naturally produces sestrin during exercise. Therefore, we are not yet at a point where our exercise replacement is a reality, but the probability of future promising results is high.

Personally, I will have to see this protein work on humans before I take seriously the idea of an exercise replacement. A successful Sestrin supplement may be able to mimic the physical benefits exercise, but obtaining physical results through minimal work could be detrimental to the public’s general mentality. Receiving physical benefits through hard exercise teaches cause and effect, mental toughness,  the value of goals, and the satisfaction of well deserved rewards. If this supplement ends up being the fantasized work out supplement everyone is looking for, how will that result-without-the-work mentality impact how we treat other aspects of society? That’s why I don’t see this discovery as a total positive, but I’m excited to see what future studies bring in the development of this long fantasized product.

If you have anything other information or opinions on this topic, feel free to drop a comment below!

 

And The Nobel Prize in Medicine Goes To…

On October 7th, it was announced that the Nobel Prize in Medicine would be awarded jointly to scientists William G. Kaelin Jr., Sir Peter J. Ratcliffe and Gregg L. Semenza for their contributions in the discovery of how cells detect and react to the levels of oxygen in their environments. Each contributor will be receiving 1/3 of the prize share for their work in this topic.

The “Textbook Discovery”

Before we are able to understand the gravity of the discovery being awarded one of the world’s most prestigious scientific prizes, let’s set up some essential vocabulary we will need to break this concept down. Firstly, HIF-1α is the main protein that has been found to be essential to the identification of Oxygen. We have known that there exists an EPO gene which encodes for a steroid known to increase levels of Oxygen but the discovery of the HIF-1α protein is what is so astounding. What this protein does is regulate the activity of the EPO gene. Another factor which plays a large role in this discovery is the VHL gene, a gene known to be responsible for preventing occurrences of cancer. It was discovered that VHL had a link to the regulation of oxygen when low levels of the gene were linked to low level of oxygen (hypoxia). However, as more VHL was reintroduced, oxygen

levels were restored to normal.

How do HIF-1α proteins, VHL genes and EPO genes come together to create an understanding for how cells react to oxygen variation? Well, for HIF-1α to degrade, a peptide known as ubiquitin must link onto the HIF-1α and begin proteasomal degradation. It just so happens to be that VHL codes for a complex which tags proteins with ubiquitin allowing them to degrade. Finally, it was discovered that Oxygen was what binded theses two together, moving ubiquitin from the VHL over to the HIF-1α protein, thus degrading it. In other words, the more oxygen there is present, the more HIF-1α which gets degraded. Finally, the mechanism by which oxygen levels are controlled has been uncovered.

The Men Behind The Discovery

Over the span of 2 decades of research, three scientists were able to form an understanding on how our bodies respond to one of the most essential molecules in biology.

William G. Kaelin Jr. is a professor of medicine at at Dana-Farber Cancer Institute and Brigham & Women’s Hospital Harvard Medical School. As a cancer researcher, Kaelin’s main contribution was in the creation of a full understanding of the VHL disease which allowed for the link between VHL and HIF-1α to be formed.

Sir Peter J. Ratcliffe is the director of clinical research at the Francis Crick Institute in London. Ratcliffe and his team’s main contribution was establishing the connection between VHL and HIF-1α.

Gregg L. Semenza is a professor in genetic medicine at John Hopkins. His work focused on the EPO gene and how it controlled oxygen levels. He found out how oxygen is regulated, leaving only the cause a mystery.

For even more information on the scientists responsible, look into this New York Times article about them.

How a Dash of Salt in the Summertime Helped Bring About Life on Earth

As humans, one of the most challenging and provocative questions we can ask is how life on earth came to be. We know about evolution, survival of the fittest, the one fish brave enough to walk. But how did the first microorganism suddenly wriggle its way out the world of the inanimate and mark the beginning of life on earth? Researchers from Saint Louis University, the College of Charleston and the NSF/NASA Center for Chemical Evolution think they have a new clue regarding the Earth’s environment at the time, and it sounds a lot like barbeque and pool party weather!

One of the keys to the creation of life is proteins. Proteins are strings of amino acids held together by peptide bonds, and they are responsible for carrying out countless tasks in the cell from catalyzing reactions as enzymes to protecting against diseases as antibodies to controlling movement and muscle contractions. Previous research has found that subjecting amino acids to “repeated wet-dry cycles”creates an ideal environment for the formation of peptide bonds. The more peptide bonds, the more complex polymer proteins that form and carry out biological processes needed for sustaining life. According to our original article, “Were hot, humid summers the key to life’s origins,” scientists imagine that the pre-life climate on earth consisted of hot, sunny days broken by heavy rainstorms. However, when Luke Bryan said that “rain is a good thing,” I don’t think he was referring to the cultivation of peptide bonds, because too much rain can actually have an opposite effect on our pre-biological proteins.

Pictured above is two amino acids joining to form a dipeptide through dehydration synthesis (removing an H2O molecule to join two monomers)

While water is the basis for all biological function, too much water added to a solution can result in hydrolysis, the decomposition of polymers due to the insertion of water molecules between bonds. If the Earth’s early climate involved large rain storms, the rain would flood the amino acid mixture and prevent the formation of peptide bonds. So, what kind of climate would then be required to spark the creation of life? Angela M. Hessler, in her article “Earth’s Earliest Climate,” tells us that “evidence points to an unfrozen — perhaps balmy — Archean Earth” due to “100–1000 times more CO2 than present atmospheric level,” which gives the Earth a “greenhouse atmosphere.” This greenhouse climate consists of high temperatures and humid weather- basically summer weather! This humidity in the air allows the amino acids to receive the ideal amount of water for forming complex proteins. However, our researchers have also discovered another factor that aids the formation of proteins, the process’s own sort of catalyst that pairs perfectly with the humid climate of pre-biological Earth.

Deliquescent minerals are salts that absorb humidity out of the air and then dissolve. If deliquescent minerals are present while amino acids bond into polypeptides, they can regulate the wetness of the environment in which polypeptides form, creating a perfect environment for the creation of proteins! I guess we can take the Bible that much more literally when were were told, “For you were made from dust, and to dust you will return.”

Above is dipotassium phosphate, a highly deliquescent mineral that is likely to have been present during the first formation of polypeptides millions of years ago.

While to some it may seem inconsequential, this discovery is important! Think about it: whenever we talk about evolution, we talk about inheriting traits from our ancestors. But we never talk about our oldest ancestor. The ancestor that has no ancestors because they are the first thing to live on this Earth! This discovery gives concrete evidence for a plausible theory regarding the birth of life on this planet, that one cell that fathered everything that now sees and breaths and strives to reproduce. This article gives us the farthest glimpse possible into the past, and with this new information, we can start to learn more about how life rose from the ground to survive and thrive on Earth.

If you have any other ideas or remarks, please feel free to comment on this post! I would love to hear what you all have to say about this exciting, new discovery!

 

Plants Have Memory!

Did you know that flowering plants can remember changes in their environment? I sure didn’t!

Flowering plants use their memory to remember the temperature of a cold winter. By doing so, plants ensure that they will only flower during the warmer temperatures of spring or summer.

The way plants do this is through a group of proteins called polycomb repressive complex 2 (PRC2). In cold temperatures, the proteins come together as a complex and switch the plant into flowering mode. However little is known about how PRC2 senses the temperature changes in the environment.

But according to an article on Science News, a team of researchers from the Universities of Birmingham and Nottingham lead by Dr. Daniel Gibbs discovered a mechanism in angiosperms that enable them to sense and remember changes in the environment so they can adapt to the varying conditions around them, especially during the changing of seasons. The researchers discovered that the protein Vernalization 2 (VRN2), the core of the PRC2, is very unstable.

Why is this important? Since VRN2 is unstable, it can be greatly affected by the level of oxygen in the environment. In warmer months, the plant is already a flower, so it does not need to continue the flowering process. The abundance of oxygen causes VRN2 to break down. Conversely, when there is a lower level of oxygen in the colder months, VRN2 becomes more stable, causing the proteins of PRC2 to come together and switch the plant into flowering mode. As Dr. Gibbs says, “In this way, VRN2 directly senses and responds to signals from the environment, and the PRC2 remains inactive until required.”

By sensing and remembering the changes in their environment, plants can control their life cycle. I find it so interesting that plants have this capability. Plants that are able to adapt to our world’s ever-changing climate will be more successful in surviving.

Programming protein pairs

Researchers from the University of Washington’s Institute of Protein Design have created a new method to engineer protein dimers, or pairs. Working alongside molecular biologists at Ohio State, the researchers have made it possible “to design proteins so they come together exactly how you want them to,” as the paper’s lead author explains.

Two proteins held together by DNA.

Before, researchers relied on DNA to engineer dimeric proteins, utilizing complementary strands to create helical proteins held together by the hydrogen bonds between base pairs. However, DNA-created proteins lack the functionality of highly active proteins like protease, while also being prone to interference during synthesis. So, longing to create these more complex protein assemblies, the researchers engineered a new way to make them.

 

Using a computer program called Rosetta, the researchers designed hydrogen bond networks for their desired protein complexes, creating complementary bond networks for each pair of amino acids. For this, Rosetta algorithmically determined the ideal shape of each amino acid chain, calculating the best way to balance out intermolecular forces and finding the resulting lowest energy level, the most probable state for each chain. Thus, the researchers could accurately design complementary protein structures, so the two parts would fit together exactly.

As a result, the researchers were able to create highly specific, more active protein dimers that form double helices unencumbered by DNA and do not form unwanted shapes or interfere with other proteins during synthesis.

This new method has the potential to “transform biomedical technology”, as scientists can now have much more control over protein interactions, potentially engineering bacteria to produce energy or designing protein machines to diagnose diseases, among many other tasks. As the researchers set their sights on more complicated, dynamic protein complexes, there is no telling what exciting discoveries await.

How Ground Squirrels Are Bracing For The Cold

https://www.flickr.com/photos/mandj98/7647426240

As we enter the heart of winter, puffy coats, hats, and gloves make it out of our closets to protect us from the frigid air. While we trudge along shivering, the ground squirrel lives happily in the cold weather, resistant to the low temperatures.

The Phenomenon:

A new study shows that when the ground squirrel wakes from hibernation, it is less sensitive to the cold than its non-hibernating relatives. Why? A cold-sensing protein, TRPM8, in the sensory nerve cells is partly responsible for the amazing phenomenon.

The Evidence:

In an experiment conducted with mice (non-hibernating), ground squirrels, and Syrian hamsters (hibernating animals closely related to the ground squirrel), the animals were given the choice between a hotter plate and a colder plate. Whereas the mice gravitated toward the hot plate, the ground squirrel and Syrian hamster did not react to the cold temperature of the plate until it dropped below 10 degrees Celsius.

The Biology:

Part of the squirrel’s and hamster’s intolerance to cold has to do with the TRPM8 protein. TRPM8 is a cold-sensing protein that sends a signal to the brain when something is too cold. Researchers turned to the gene responsible for turning on the TRPM8 protein to find the differences between a ground squirrel and a rat. They found a chain of six amino acids in the squirrel gene that caused the adaptation to cold. When they switched that section with one from a rat, the squirrel was more sensitive to the cold.

It is quite amazing that scientists can extract and switch such small portions of DNA to find the exact cause of a trait. What else do you think this technology could be used for?

The Effect on Life:

Tolerance to cold may help the squirrel and hamster transition from an awake state to hibernation state. This is true because if an animal senses or feels cold, it will expend a lot of energy trying to warm itself up. This process counters they physiological changes needed to transition into hibernation, a state of low metabolic activity. Hence, since the hamster and squirrel don’t sense the cold, it will be easier to hibernate.

Further Research:

There is still a lot unknown about the TRPM8 protein and ground squirrel temperature sensitivities. It is believed that TRPM8 is only a part of their intolerance to cold. Furthermore, the structure and function of TRPM8 is still being studied and could lead to more breakthroughs. Want to learn more about ground squirrels, hibernation, or the TRPM8 protein? Click here to read the full article!

Hair Saving Option with Chemotherapy

Scientists have been finding a way to prevent hair loss after the painful process of cancer treatment, Chemotherapy (Chemo). Hair loss is one of the biggest feared side-effects. A recent study showed that 75% of female patients who had breast cancer feared the side effect of losing hair. Hair loss scored the highest in a Swedish nurse’s study that investigated the quality of life in patients who had breast cancer. With the help of Sung-Jan Lin, a scientist at National Taiwan University, a protein was made that could withstand the distressing effects of Chemotherapy.

There are a few other options for people receiving this treatment. Some will try to put on scalp-cooling caps to freeze the chemo drugs from entering the hair follicles. However, this process is expensive and only works for 50% of the people. The treatment could end up being longer than expected, and can cause mild to severe headaches and discomfort.

Lin describes that part of the problem is that we have such a limited knowledge of how Chemotherapy damages hair follicles.

In short, his team looked at a protein called p53. This protein functions to limit tumor growth, but also helps suppress hair growth (hair cells divide rapidly like tumor cells)

Studying P53, Lin found out that the protein was blocking a hair-promoting protein WNT3A. This stimulated his team to ask the following question. Is injecting WNT3A directly into the scalp while administering Chemo prevent hair loss?

The team decided to experiment with mice with a chemotherapy agent, and soon enough the results matched their hypothesis. One group of mice were injected with WNT3A soaked beads. And sure enough, that group sustained their hair. While the other group that was not given WNT3A loss all their hair.

Lin and his team are now working to adapt his studies on human patients. As stated by Lin it would be unsafe to inject WNT3A in bead form. As a result, they are working to create the protein in a gel or cream solution.

With this new hair saving option, the cancer treatment will seem less fearful for some patients. This treatment could be a big help for the future. Scientists are working to expand their knowledge on how to effectively provide treatment without endangering our human traits.

So after hearing all this, what do you feel about this new idea? Will the “power of proteins” eliminate other side effects provided by Chemotherapy? If so, what kinds? Let me know in the comments below.

Photo link and photographer:

www.flickr.com/photos/calliope/6025359063

Liz West

Design Your Own Organelle!

What?

All eukaryotic cells consist of compartmentalized organelles, each with a specific function. We’ve all heard of mitochondria, chloroplast, and lysosomes, but, what if we could design a new organelle?! That’s exactly what scientists are working on right now – modifying or hijacking existing organelles to fit new specific functions.

Why?

Scientists currently have the technology to alter the DNA of cells to manufacture proteins they couldn’t “naturally” make. However, this technique has a few flaws. The proteins produced or their intermediates could damage the cell and chemicals in the cell could damage the proteins. If we could compartmentalize the production of these new proteins, this problem would be avoided. So, we look to organelles!

How?

Stuart Warriner, a chemical biologist at the University of Leeds, and his colleagues believe peroxisomes are the key. Current techniques allow scientists to manipulate these organelles. Their experiments show that they could deliver certain proteins into the peroxisomes of most cells. These selective proteins are ones that are not usually made; therefore, we say that humans have “hijacked” the cell.

https://commons.wikimedia.org/wiki/File:OSC_Microbio_03_04_Peroxisome.jpg

What’s Next?

Scientists are hopeful that future research could lead to the ability to use peroxisomes to manufacture compounds by importing specific proteins into them. Currently, when an organelle is modified, every organelle of that type must be modified. Future research could ensure that modified and conventional organelles could coexist in the same cell. In addition, Warriner and his team are working on the modification of peroxisomes in yeast to produce desirable compounds. Despite these studies, Warriner believes that this technique of hijacking organelles will not be implemented in humans for decades, if not never, because it wouldn’t be particularly useful. To learn more, check out their findings!

Who Cares?

We have the ability to alter DNA and cells! That is amazing! Although peroxisome altercation may not prove to be essential to humans, it is still an impressive exploratory feat and a step toward greater modification in microscopic organisms. What do you think similar cell modification research should be focused on?

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