#MicroTwJC 47: Total Synthesis of a "Functional" Designer Yeast Chromosome

#microtwjc Clostridium difficile

In this week's #microtwjc paper, we discuss a preliminary study that asks whether common acid reflux treatments make Clostridium difficile virulent. 
If ever you have suffered from acid reflux, then you may have been prescribed a "proton pump inhibitor". These act, as you may have been able to guess, on proton pumps within the gut. so what do proton pumps do ?
Proton pumps keep your stomach acidic
In order to keep your stomach acidic, proton pumps act to pump protons (also known as hydrogen ions) into your gut. But in cases where your gut produces too much acid, doctors can prescribe proton pump inhibitors such as Omprezole. They stop the proton pumps, and thus prevent the build up of stomach acid. This de-acidification of the stomach can leave someone vulnerable to gastric infections. A systematic review has shown that proton pump inhibitor treatment is associated with infections by bacteria such as Salmonella, Campylobacter, and Clostridium Difficile *.

What reading a scientific paper reveals about you

What do you believe science is ? How do you think that belief affects your life ?

One way of answering t comes from the way we treat the foundation upon which modern science is built.

The medium that scientists use to communicate their discoveries is the scientific paper. These documents have evolved over the centuries to adapt to the way that science itself has changed. The first scientific journals came into being in the 17th century, in a time when science was more of a hobby for the aristocracy than a significant career in itself. These early papers lack much of the structure of modern journals, and can be disconcertingly easy to read compared to their modern counterparts. But as science became more professional, readers demanded greater transparency to allow them to replicate the experiments they read in the journals, the modern scientific paper came into being.  I'm going to make a fairly big generalisation by saying a scientific paper's structure* consists of five parts 

• Introduction- Where the authors explain the background of their research. This will reveal to the reader the questions that they intend to ask during their paper, and why those questions may be important.
• Methods- This is where the authors explain how they are going to use the materials they have to hand to answer the questions they have posed in the introduction. This is the part where they put in a lot of the important details of how they set up their experiments.
• Results- Here, the authors explain what they have observed from their experiments, usually in some detail. A savvy reader should be able to see how these observations contribute to answering the overarching "question" of the paper. But for those who can't, there is always...
• The Discussion. Where the authors explain how their observations fit in with what everyone else has published in the scientific literature. They can also take this opportunity to point out where their experiments fall short, and what other questions have been raised or left unanswered by their work.
• References. In any academic article, it is important to cite the work of others, so that the readers can find their work and verify that the author is actually representing it properly, or not. It also allows the author to make their article shorter, simply by pointing to other works which may have already explained their experimental procedures and the concepts they are working with. These are also incredibly important for recognising others in the field who have contributed important research.

When I first started reading papers, it was for writing up specific essays or dissertations. I learned early on that if you spam your bibliography with enough references, you would get better grades. To insure against disaster, such as someone actually reading the reference section, I would read over the abstract to see whether it backed up whatever point I was trying to make.
Soon, my technique had advance to the point where I would read the abstract and the introduction, and then skip to the discussion. I saved time by ignoring the parts of the paper which I didn't understand, and could still competently comment on its findings. I could "read" a ton of papers using this technique, and still had plenty of time to go out partying. I had hacked my undergraduate degree.
Things changed when I started working in a scientific lab. If I wanted to learn a new scientific technique, I had to delve into the methods and the results sections of academic papers. Before I could easily transcribe what the authors of these papers wanted to say by reading the introduction and discussion.  Now, I could put myself in their shoes, and see how they decided to answer the questions posed in the paper. I could see how I could do things differently, and more importantly I could see when someone was doing something better, and then use that for my own work. Soon I realised that I wasn't getting the whole picture the way I read academic papers previously. It was not just about reading the methods and the results, it was also about delving through the references sections, to immerse oneself entirely into the experience. Only then can you see the potential gaps in knowledge left by a paper and fully understand what it is actually saying.

But you didn't start reading this for me to tell you what a scientific paper is, or to learn my life story. You want me to tell you about what reading a scientific paper reveals about you, and what you believe science is.
I still run into scientists who only read the introduction and discussions of papers without ever fully engaging with the content. By doing that, they have implicitly made the decision that science is a collection of facts arbitrarily espoused from on high that need to be memorised.
But if you believe that science is more like conversation based on careful analysis of the evidence, then you need to engage with the evidence presented within the paper. If you do manage to delve into these parts of the paper, if you use every tool available to you to understand a paper, to put yourself in the authors shoes, then you'll see the problems they faced as they did, and how they overcame them.
Without that insight, without that knowledge of what goes into science, we end up losing out, and the discourse on science is the worse for it.

*I should note that your mileage may vary for this structure. There are some shorter papers which dispense entirely with the methods, and include them all with the results. If you are reading the medical literature, you may come across case reports, which have a slightly different structure because often the Doctor doesn't seek out the question, the question finds them in the form of a patient with an odd manifestation of a disease.

 If you are reading a paper with no results or methods, then the document you are holding is most likely a review of the literature, and completely different to the kinds of articles we are discussing here.

Taking DRACOnian measures against viruses

When Alexander Fleming shamelessly took credit for a drug produced by the penicillium bread mould, our fight against bacteria completely changed. Even now, bacterial diseases are nowhere near the threat they were before that discovery. But today, we are seemingly having to put up with emerging viruses. Every year, we have to put up with entirely new strains of flu. There is nothing we can do about the viruses that cause the common cold. There are various antivirals out there, but they are specific for specific diseases, like flu, or HIV.
Generally, it’s been fairly difficult to make anti-viral drugs. Often, a lot of the problem comes from the way viruses work. When they are outside the cell, they don’t have any active metabolic processes that can be targeted by drugs. And when they are inside the host cells, the metabolic processes they’re mostly using are ours. So it’s very hard to target the viruses without attacking the host. Compared to bacteria, viruses present a very small target. 
Could a paper published in PLOS One called  “Broad Spectrum Anti-viral Therapeutics” represent a penicillin moment for viruses ? A trailblazer that can transform our relationship with viruses ? To work this out, let’s take a good long look at what these anti-viral therapeutics are, and what they do.  To do that, we have to talk about DRACO.

Are we talking about the DRACO from Harry Potter, or the dragon voiced by Sean Connery in Dragonheart ?

Whilst I compliment you on your knowledge of pop culture, you are wrong on both counts. DRACO is a handy acronym that stands for Double-stranded Ribonucleic acid Activated Caspase Oligomizer. DRACO is the drug that is being purported to extinguish all of those nasty viruses. To understand how it works, we need to take a look at how some of our most pernicious viruses work.
You may have heard about DNA, and how it’s genetic code is a blueprint for life. Your genome is encoded in your DNA. The nucleus of your cell holds all of the DNA, and acts like a library for your genetic code. When your cell needs a specific genetic code to make a certain protein, the nucleus makes an RNA copy of the appropriate gene and sends it out into the rest of the cell, where it can be used to construct a protein.
The goal of a virus is to enter a cell, and to hijack this process to make more viruses. Usually at some point, the virus will attempt to substitute it’s own genetic code for that of the host cell, tricking the host cell to make more viruses ^[1].
However, some viruses can store their genetic code using RNA only. Whilst RNA is less stable than the DNA, it means that these viruses can go straight to the cell machinery that translate RNA into protein, and get ahead with making virus based proteins.