prion proteins

Cannibalism can be very dangerous to the body. You open yourself up to more diseases eating human flesh. Viruses tend to be very specific to a species, and it is rare for them to jump. So if you are eating beef meat contaminated with some virus that is affecting the cow, chances are you won’t catch it. But if you are eating human flesh, that is contaminated with HIV, you now have a very good chance of contracting it. Kuru is a disease that spreads almost exclusively by cannibalism. It is a mutated prion (protein) that can spread to surrounding brain matter. Resulting in a loss of motor control, impaired cognitive abilities, uncontrolled laughing, swelling in joints, and eventually death. (Source)

  • the working hypothesis is that they’re misfolded proteins that catalyze the misfolding of healthy versions of the same protein, eventually causing plaques of misfolded protein to accumulate in the brain
  • how do prion proteins get into the brain?
  • mice with the normal version knocked out are not perfect, but too functional to elucidate what, exactly, it does
  • prions are extremely hard to destroy (ionizing radiation doesn’t work, proteases don’t work, high temperature doesn’t work). a combination of high pressure, temperature, and concentrated corrosive chemicals seems to work.
  • over 100,000 food cows had mad cow disease but ~170 humans have been diagnosed with it since the British outbreak in the 1990s
  • surely more than 170 were exposed–extremely long incubation period, or do we have no fucking clue how prions work?
  • given their indestructibility, if the working hypothesis about prion transmission is correct, why is everything not prions? 
  • (this is comforting, but confusing)

Prion-like protein spotted in bacteria for the first time

Prions, the infectious agents best known for causing degenerative brain disorders such as ‘mad cow’ disease, may have been spotted in bacteria.

A section of a protein in Clostridium botulinum, the microbe that causes botulism, can behave like a prion when it is inserted into yeast and Escherichia coli bacteria, researchers report in the 13 January issue of Science1.

Prions are formed by proteins that can fold in a number of structurally distinct ways. A prion version of a protein can perpetuate itself in an infectious manner by converting normal forms of that protein into the prion version.

Scientists first discovered prions in the 1980s as the agents behind fatal brain disorders known as transmissible spongiform encephalopathies. Since then, researchers have found the misfolded proteins in mammals, insects, worms, plants and fungi2, and learned that not all prions harm their hosts.

But until now, prions were only seen in the cells of eukaryotic organisms, a group that includes animals, plants and fungi.

Clostridium botulinum harbours a protein that acts like a prion in other bacteria. James Cavallini/SPL

Types of Pathogenic Microorganisms

The average human body contains about 10 trillion cells. Imagine how much that is! If our population was 1400 times greater in the entire world, then we still would not be more than the number of cells in the entire body. Amazing isn’t it? 

But what if I tell you the gut alone, contains 100 trillion microorganisms living within it this very minute? And hence the picture above, our world is really a microorganism’s world, we are simply the ones large enough to be seen. 

And thus we see the importance of microbiology, how exactly are these microorganisms affecting our lives? 

Most of these microorganisms are actually beneficial to our body, for example, by aiding in the process of digestion, however, there are microorganisms that are damaging to their host, either by the production of toxic products, or direct infection, and these microorganisms are termed pathogenic. 

To have an idea of this, let us talk about the types of microorganisms, and the pathogenic ones in each type, that is, the one that can give us a disease. 

Microbes that Cause Diseases

Microbes that cause diseases can be divided into 5 groups of organisms:

  1. Bacteria
  2. Fungi
  3. Protozoa
  4. Helminths and Rotifiers
  5. Viruses

There is also a recently discovered type of microbe that can cause a disease, known as a prion. 

Of these microbes, we can classify them in several different ways. 

Classification of Microbes:

Firstly, it is important to consider the status of prions and viruses. Technically, these “microbes” are not living. Prions are simply misfolded proteins, and viruses are only “alive” when they infect an organism. Thus, both prions and viruses have their own classifications. 

As for the other organisms, we can classify them in several ways:

  • Eukaryote vs Prokaryote
    • In this classification scheme, all bacteria are prokaryotes, and fungi, protozoa, helminths and rotifers are eukaryotes. 
      • The prokaryotes are further subdivided into eubacteria and archaebacteria. Eubacteria are the medically important bacteria, while archaebacteria are a group of evolutionarily distinct bacteria. 

Differences between Eukaryotes and Prokaryotes:

  • General Size
    • Eukaryotes are much larger than Prokaryotes, being about 10-100mm in diameter. 
    • Prokaryotes are much smaller, being about only 0.2-2mm in diameter. 
  • Nucleus vs Nucleoid: 
    • Eukaryotic cells contain a true nucleus, with multiple chromosomes, linear DNA, and a nuclear membrane, using mitotic apparatus to ensure chromosomes are equally distributed to the daughter cells. 
    • Prokaryotic cells contain a nucleoid, which is an area of loosely organized, circular supercondensed DNA, lacking nuclear membrane and mitotic apparatus.

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ELI5: Getting sick from a 'bacteria' vs. 'virus'

Bacteria produce harmful chemicals as part of their life processes. They use up your body’s resources (like eating your sugar or even eating your cells) and spit out toxic waste. Sometimes that waste is specifically designed to protect the bacteria by killing your immune system cells that try to attack it. But it also just basically poops all up in your body, which causes some damage. The symptoms of bacterial infections are related to what waste products the bacteria produces and where the bacteria is living. Your body fights bacterial infections by basically eating them, along with some other toxic chemicals that destroy them.

Viruses hijack the DNA in your cells to make more of the virus. They invade the cell and tell it to stop doing whatever it’s doing that your body needs it to do, and instead all it does is manufacture more of that virus. Eventually, the cell dies - usually by literally exploding - when it fills up with copies of the virus. Those viruses go on to infect other cells. Viral symptoms are caused by your body’s own attempt to kill them, and by the deaths of the cells they’re infecting. Your body fights viruses also by eating them, but it’s harder because they’re a lot smaller and have special protein shells that disguise them as “totally not a virus don’t eat me you guys”.

For extra fun, there are also prion diseases! Prions are proteins that folded the wrong way. When properly-folded proteins come into contact with prions, they re-fold into the same wrong shape as the prion. Your body can’t do anything about it because although it’s folded wrong, it’s still a protein that’s supposed to be there. Proteins are the way your body communicates and accomplishes certain things, so folding them wrong can really muck-up what is supposed to happen. In the case of Mad Cow Disease, as more and more proteins turn into prions, your brain turns to mush and gets holes in it until you go crazy and die.

If you think of your body as a factory that builds cars: bacteria are like a drunk hobo sneaking into your factory and dumping empty wine bottles into the machinery so it breaks. Viruses are like a roomba wandered in and reprogrammed your factory to start making more factory-invading roombas instead of cars. Prions are like a weird European car showed up and crashed into one of your factory’s cars after it left the factory, and now they both keep crashing into other cars (which then go on to crash into more cars) and also they all keep crashing into your factory.

Also fungal infections. Fungi can’t produce their own food, so they steal yours. Often that means invading parts of your body to get to it, and dumping toxic waste like bacteria. In the factory, a fungus would be someone building a shed attached to your factory and stealing your power so your factory doesn’t have enough to run and dumping garbage into your factory.

Also also, parasites. Parasites do the same thing as bacteria, but they’re [often] multicellular, so they’re much larger. Instead of a bunch of them, it’s usually a few big ones (although sometimes also a lot of them). In the factory, a parasite would be like the mafia moving into your factory, breaking stuff, and punching you right in the kidneys (or more likely, in the intestines) while they steal your money.

Explain Like I`m Five: good questions, best answers.

Plant protein behaves like a prion

Prions, the misfolded proteins that are known for causing degenerative illnesses in animals and humans, may have been spotted for the first time in plants.

Researchers led by Susan Lindquist, a biologist at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, report that they have found a section of protein in thale cress (Arabidopsis) that behaves like a prion when it is inserted into yeast.

In plants, the protein is called Luminidependens (LD), and it is normally involved in responding to daylight and controlling flowering time. When a part of the LD gene is inserted into yeast, it produces a protein that does not fold up normally, and which spreads this misfolded state to proteins around it in a domino effect that causes aggregates or clumps. Later generations of yeast cells inherit the effect: their versions of the protein also misfold.

This does not mean that plants definitely have prion-like proteins, adds Lindquist — but she thinks that it is likely. “I’d be surprised if they weren’t there,” she says. To prove it, researchers would need to grind up a plant and see whether they could find a protein such as LD in several different folded states, as well as show that any potential prion caused a misfolding cascade when added to a test-tube of protein. Lindquist adds that because she’s not a plant scientist — her focus is on using yeast to investigate prions — she hasn’t tried these experiments. The study is reported on 25 April in the Proceedings of the National Academy of Sciences1.

A protein in thale cress (Arabidopsis, pictured) behaves like a prion when it is expressed in yeast. Kristopher Grunert/Corbis/VCG
Genetic mutation blocks prion disease
Unknown mechanism helped some people in Papua New Guinea escape historic, deadly outbreak.

Scientists who study a rare brain disease that once devastated entire communities in Papua New Guinea have described a genetic variant that appears to stop misfolded proteins known as prions from propagating in the brain1.

Kuru was first observed in the mid-twentieth century among the Fore people of Papua New Guinea. At its peak in the late 1950s, the disease killed up to 2% of the group’s population each year. Scientists later traced the illness to ritual cannibalism2, in which tribe members ate the brains and nervous systems of their dead. The outbreak probably began when a Fore person consumed body parts from someone who had sporadic Creutzfeldt-Jakob disease (CJD), a prion disease that spontaneously strikes about one person in a million each year.

Scientists have noted previously that some people seem less susceptible to prion diseases if they have an amino-acid substitution in a particular region of the prion protein — codon 1293. And in 2009, a team led by John Collinge — a prion researcher at University College London who is also the lead author of the most recent analysis — found another protective mutation among the Fore, in codon 1274.

Continue Reading.

OB Science Time: The Castor Disease

Episode 3x03 had a lot of science in it, so it’s time for a second edition of OB Science Time to discuss the science behind the Castor Disease, or “glitching”.

Scott says, upon examining Seth’s brain that “it looks like Swiss cheese” and he mentions encephalopathy as well as Creutzfeldt-Jakob disease. Encephalopathy is an umbrella of diseases categorized by an altered mental state, including symptoms such as loss of cognitive function, subtle personality changes, and inability to concentrate. We certainly saw these symptoms in Seth, with his inability to perform well on Paul’s syllogism test, as well as his violent outburts and his mutterings in the stairwell before his final episode.

Creutzfeldt-Jakob disease is caused by prions, which are misfolded proteins that then act as an agent to convert their properly folded counterparts into more prions. The classic result of these prions is a change in the gray matter of the brain, causing large vacuoles to form, giving the appearance of Swiss Cheese. Symptoms of this disease include memory loss, personality change, and hallucinations, as well as jerky movements and seizures.

My guess is that the Castor disease functions in a similar manner as these diseases. Scott also mentioned the presence of amyloid plaques in Seth’s brain, which are protein aggregates. These aggregates, which could be made up of prions, could be causing neurodegeneration, leading to the Castor glitches and altered mental states.

It will be interesting to see what Cosima and Scott do with this knowledge, and more importantly, how the Castor clones will go about finding a cure for their malfunction.

My ask is always open for any questions or comments, and you can find more OB Science Time here!! :D

OB Science Time: The Clone Disease

What an episode that was! After all the information we learned in 3x06, I have decided to devote an OB Science Time to discussing the clone disease.

The most exciting revelation for me was that the Castor and Leda diseases are really one and the same. The disease is caused by a misfolded protein, which can be referred to as a prion. The protein misfolds and disrupts function, and then causes tissue degradation. In the case of the Castor clones, the brain degrades, while in the case of the Leda clones, the endothelial tissue degrades, beginning with the uterus and then spreading to the lungs and other organs.

Unfortunately, the Castor clones can also transmit this disease sexually, as well as via blood. The women in the notebooks that the Castor clones slept with all ended up with the prions in their blood, and degradation of the ovaries leading to sterilization. Dr. Coady had plans to harness this sterilization ability and use it as a weapon to essentially wipe out enemies via sterilization.

Sarah, and of course Helena, are unique in that they are Leda clones that should have the defect, yet they are fertile. It appears that something in their DNA prevents the prion from attacking their bodies. This may mean that the twins could be useful in developing a cure, as their genetics may hold a sequence that could be used for gene therapy, or something about their biology could lead to a cure.

I’m excited to see where the show will go from here, now that Coady’s work has been blown up and Sarah and Helena have escaped. My ask is open for all discussions and questions :D