The Inside Story – Receptor-Mediated Endocytosis in Drug Delivery: By Jacob Cortez

Whenever someone gets sick, they need some form of treatment. Treatment can be a natural remedy or, most likely, a drug. In the case of more serious illnesses such as cancer, the only treatment is medicine. Medicine has been used to treat illness for most of the modern age, and you are probably familiar with many drugs. Have you ever wondered how those drugs work?

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http://www.reactiongifs.com/magic-3/

Close but no cigar.

A lot of anti-cancer drugs rely on clathrin-dependent receptor-mediated endocytosis. Now, that might sound a little complicated, but I’m going to break it down for you. Clathrin is a kind of coating protein for vesicles, little balloon-like sacs that allow different substances to enter a cell. These vesicles are created from the cell’s membrane after the target substance’s ligand binds to a receptor. Once the receptor binds a ligand, a vesicle is created, and the substance enters the cell within the vesicle. This is called receptor-mediated endocytosis. Neat, right?

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https://knowyourmeme.com/photos/361023-neat

Two of these ligands are transferrin and riboflavin. Transferrin binds iron and is a good target for drug delivery. Because transferrin travels across the blood brain barrier to deliver iron to the brain, it can be used to ferry drugs through the blood brain barrier to treat diseases that target the brain. Riboflavin is another important ligand for drug delivery. Early data suggests that riboflavin could be beneficial in drugs targeting breast cancer. The carrier protein that binds riboflavin has been found in increased levels in cancerous breast tissue, so the drug would have an easier time finding the tumor.

Receptor-mediated endocytosis is essential to many cell functions. Because of its necessity, it is very useful for drug delivery. New drugs are being developed every year, and, soon, we may have a easy way to fight cancer.

References:

Bareford, Lisa M and Peter W Swaan. “Endocytic mechanisms for targeted drug delivery” Advanced drug delivery reviews vol. 59,8 (2007): 748-58.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2000329/

 

 

 

 

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Bacillus subtilis and Tetrahymena thermophila: By Camille Hart

If you are like me, when you see the names of these two organisms you are more worried about pronouncing them right than worrying about how they interact with their microscopic worlds. However, these small organisms are quite significant to our world! Bacillus subtilis are small bacteria that exist in the gastrointestinal tracts of many organisms. Including you! To be able to live in such an extreme environment, these little bacteria have evolved a unique set of armor. They surround themselves with multiple extracellular layers, one of the outermost layers being known as the spore coat. This layer protects these little bacteria from another microscopic organism, Tetrahymena thermophila, which would otherwise eat them in a process known as phagocytosis.

Phagocytosis by bltshop

Phagocytosis

The spore coat that helps to protect this little bacteria is more beneficial than you might think. Not only does the coat deter the ciliary protozoans, Tetrahymena thermophila, but it can also act as a guard against lytic enzymes. If the bacteria were to come into contact with these enzymes, the cell wall beneath the coating would be degraded. However, with this coat in place even if the bacteria are ingested, they cannot be digested, ensuring that the bacteria are able to live on.

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http://www.tumblr.com/tagged/phagocytosis?language=nl_NL

So what is the moral of this story? Why should we care about these little bacteria and their unique sets of armor? Well, while it has not been proven that the spore coat can actually protect the bacteria from being eaten, it has been shown that these coats can protect the bacteria from harmful lytic enzymes. If this spore coat was able to be replicated and put into applicable use in protecting our own cells, imagine the possibilities!

References:

Klobutcher, L. A., Ragkousi, K., & Setlow, P. (2006). The Bacillus subtilis spore coat provides “eat resistance” during phagocytic predation by the protozoan Tetrahymena thermophila. PNAS. 103:165-170.

Cell Signaling and Cancer: Justin Waguespack

If there was a dictionary for all the scary words in the world, cancer would be near the top, with college as a close second. Cancer is one of the leading causes of death world-wide because of its devious nature. Cancer cells have the ability to attack different types of cells to avoid apoptosis which is the death of a cell that is harmful or may not be functioning properly. In 2003, the Beatson International Conference on Cell Signaling and Cancer took a closer look at cell signaling as a possible mechanism to combat cancer.

Cancer 3http://www.quickmeme.com/SURVIVE

Cell signaling is continuously happening throughout our body, and it allows for growth, cell structure, respiration, muscle signaling, and almost any other process that allows our bodies to function. The problem with cancer cells is that they are unstable and cause mutations in normal cellular signaling processes. Late detection and symptoms of cancer often lead to high mortality rates, and it can be tricky to kill the evasive cancer cells without attacking healthy human cells.

Cancer 4https://themighty.com/2017/11/funny-cancer-memes/

One method the Beatson International Conference on Cell Signaling and Cancer discussed as a possible method to prevent cancerous cell growth was to use cell signaling inhibitors. Remember, cancer cells are evasive and can attack multiple cells, but Raf proteins were discussed at the conference as a possible target for therapeutics. The Raf protein is special because it can form three different conformations. The most abundant conformation is the B-Raf. Mutations to the B-Raf protein is commonly found in melanoma and other types of cancer. The Institute of Cancer Research, Landon found that mutations of the B-Raf protein can be blocked by downregulation of RNAi. This finding is significant because blocking the B-Raf protein from being mutated would allow for the cancer cells to undergo apoptosis. The conference may not have created a solution to stop cancer completely, but understanding the relationship between cell signaling pathways and cancer cells is a huge step in the fight against cancer.

References:

Martin, G S. (2003). Cell Signaling and Cancer. Current Neurology and Neuroscience Reports. U.S. National Library of Medicine. 4:167-173. Print.

Modulation of Phagocytosis in Tetrahymena thermophila by Histamine and the Antihistamine Diphenhydramine by Shelby B.

Almost anyone would agree springtime is enjoyable- with the nice weather and all those pretty flowers blooming- but no one enjoys the itchy, puffy eyes, sneezing, and congestion that come with spring allergies! If the symptoms are very bothersome, you may take an allergy pill to get some relief. Most people don’t think much about it, but this is an example of histamines and antihistamines working in your body and affecting your daily life!

Funny, Happy, and Weather: When ur happy the warm weather is
 finally here but the pollen count is 1 million
Relate-ability to the max. (@tank.sinatra)

Histamines are molecules in the body that cause allergy symptoms and swelling. Antihistamines counteract or reduce the effects of histamines. For example, diphenhydramine, also known as Benadryl, is an over-the-counter antihistamine you have probably used at least once in your life. Diphenhydramine is cheap and easy to obtain, making it useful in studying histamine/antihistamine effects.

When studying molecules that have an effect on the human body, it is important to use model organisms. A great model organism is one that reacts similarly to humans to a certain stimulus (in this case histamines/antihistamines) and is easy to obtain, grow, and examine. This definition is why many researchers use Tetrahymena spp. , single celled organisms that behave very similarly to human immune cells and are cheap and easy to keep alive and observe.

In this illustration, a eukaryotic cell is shown consuming a bacterium. As the bacterium is consumed, it is encapsulated into a vesicle. The vesicle fuses with a lysosome, and proteins inside the lysosome digest the bacterium.Image result for macrophage phagocytosis

*An example of phagocytosis in Tetrahymana spp. and a human immune cell*

       A study by Buduma et. al. used Tetrahymena thermophila to test the effects of histamines and the antihistamine Benadryl on the rate of phagocytosis (food uptake) of the cells. It is important to study this because human immune cells use phagocytosis in our bodies to keep us healthy, and histamines and antihistamines affect this process. The study found that histamines had no effect on the Tetrahymena, but the Benadryl decreased phagocytosis, which meant the cells had a receptor for antihistamines but not histamines. These results mean Tetrahymena thermophila can now be used to test the effects of new antihistamine drugs quickly and easily!

References:

Buduma, N., et.al. (2013). Modulation of Phagocytosis in Tetrahymena thermophila by Histamine and the Antihistamine Diphenhydramine. ACTA Protozoologica, 52, 317-323. doi:10.4467/16890027AP.13.029.1321

Pictures:

https://courses.lumenlearning.com/wm-nmbiology1/chapter/animal-cells-versus-plant-cells/

https://me.me/i/when-ur-happy-the-warm-weather-is-finally-here-but-13469122

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

Plants as Epigenetic Models: Brooke Savoie

There are more factors that control the way organisms look and function beyond the realm of genes. The genotype, or genetic composition of an individual was thought to solely determine the characteristics of that individual. Epigenetics is the change in how genes are expressed without actually changing that gene itself. The expression of genes can be changed by things such as environmental factors, so even organisms with identical genetic compositions can be different.

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Some epigenetic information can be passed down to further generations. Source

Plants have been used in the study of epigenetics due to their versatility. Plants can be easily modified and are so diverse that they are the perfect candidate. For plants to survive in their environment they must be adaptive and overcome adverse conditions such as weather. Because of the non mobile nature of plants they must be able to adapt since they can’t just get up and move. It was found that plants have the same types of gene regulation that many eukaryotic organisms. Arabidopsis thaliana which is a mustard plant has been the center of epigenetic studies since it was the first plant to have its genome sequenced. With the mustard plant, individuals with the same DNA sequence had variable expression of genes which contributed to the time of their flowering. In response to different environmental factors a plant can modify the expression of genes that can help the plant survive and thrive in it’s specific circumstances.

Plant models have given insight to how gene regulation and expression occur in other organisms. Plants and animals may seem completely different but there are more similarities than meet the eye. Both plants and animals have the similar ways of controlling gene expression through methylation of DNA. A genetic disorder that was first found and studied in maize was also found to affect humans which is caused by a phenomenon called parental imprinting. For every gene only one variation or allele is expressed in an offspring the other allele must be silenced, either the one from the mother or the one from the father. Parental imprinting can have some mutations and is the reason for some disorders which is a good reason to study how this mechanism works in plants.

Because of the agricultural industry the study of epigenetics may have some implications in how to grow more successful and resilient crop. Epigenetics of wild mustard are the reasons for the vegetable variety that we enjoy today. The variability of the expression of traits allow for such so much variety in plants.

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All the plants above were derived from the selection of wanted traits from wild mustard plants. Most of the vegetables are of the same species Brassica oleracea. Source

References:

Pikaard, C. S., & Mittelsten Scheid, O. (2014). Epigenetic regulation in plants. Cold Spring Harbor perspectives in biology6(12), a019315. doi:10.1101/cshperspect.a019315

(2009). Genomic imprinting disorders in humans: a mini-review. Journal of assisted reproduction and genetics26(9-10), 477-86.

https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi

Pictures:

https://www.google.com/search?q=epigenetic+meme&rlz=1C1CHBF_enUS812US812&source=lnms&tbm=isch&sa=X&ved=0ahUKEwjU9OjesKneAhVJPK0KHY2HCTwQ_AUIDigB&biw=1745&bih=853#imgrc=OHabdFZuAov25M:

https://www.google.com/search?q=epigenetic+plants&rlz=1C1CHBF_enUS812US812&source=lnms&tbm=isch&sa=X&ved=0ahUKEwib8O6owKneAhURna0KHfUdCqsQ_AUIDigB&biw=871&bih=844#imgrc=Ej1ZxvV-bsDRRM:

 

Using Molecular Approaches to Combat Illegal Wildlife Trade by Emily Ford

The illegal trade of wildlife (plants, animals, and their byproducts) is the second largest threat facing endangered species today, outranked only by habitat destruction. Frequently trafficked species span all ecosystems in every part of the world, making the $20 billion/year market incredibly difficult for law enforcement to handle. Most trade occurs along existing drug smuggling routes, and once wildlife is seized, it’s often tough to pinpoint where exactly these species came from– that’s where molecular genetics comes in.

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Turtles are one of the most threatened species worldwide, with 51% of their species extinct, endangered, or vulnerable of becoming endangered. (Image source)

In the past, identifying trafficked organisms was based primarily on recognizing physical traits unique to each species. Unfortunately, this requires the plant or animal to be mostly intact, and is almost useless in identifying the origins of byproducts often seized (such as ivory, cooked/dried meats, feathers, etc.); however, molecular approaches require only a small sample of DNA, making them the preferred method of species identification in these instances.

Each cell contains multiple copies of mitochondrial DNA (mtDNA) because there are several mitochondrion inside. Plant and animal cells only contain one nucleus a piece (generally), meaning that mtDNA is more likely to be found in a sample (like decomposing tissue) than nuclear DNA (nDNA). Segments of mtDNA can be copied over and over again using a process known as the polymerase chain reaction (PCR), which allows genes (like Cyt b or CO1) to be identified easily. The differences in DNA patterns within these genes is what makes each species unique– that’s how they’re able to be identified. heraa-hashmi-atcaveheraa-mitochondria-is-the-powerhouse-of-the-cell-false-mitochondria-are-the-powerhouses-of-the-cell-mitochondria-is-plural-the-singular-is-mitochondrion-if-thats-the-o

Having multiple mitochondrion in each cell makes mtDNA the preferred genetic marker for identifying a degraded sample’s species of origin. (Image Source)

In terms of conservation efforts, simply identifying a species isn’t enough– it’s important to determine where these organisms are starting their trafficked journey. “Phylogeography” refers to the relationship of very similar genetic patterns (like those found in mtDNA) and their location across the globe. A species’ region of origin can be determined by comparing it’s mtDNA sequences to what we already know about the mtDNA of similar species living in different parts of the world.

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Phylogeographic methods were used to compare seahorse species Hippocampus barbouri, H. spinosissimus (pictured here), H. trimaculatus, and H. ingens to pinpoint the birthplace of seahorses listed for sale in Californian traditional medicine shops. (Image Source)

Not only is the trafficking of species cruel to individual organisms, it disrupts their home ecosystems by removing key players from their natural balance, while simultaneously exposing species to foreign diseases they have no immunity against. The methods described above, in part with harsher legal consequences for traffickers, can help decrease illegal wildlife trade, therefore improving the overall health of species everywhere.

Source: Alacs, et al. (2009). DNA detective: a review of molecular approaches to wildlife forensics. Forensic science, medicine, and pathology. DOI: 10.1007/s12024-009-9131-7.