Thursday, September 4, 2014

Sunshine and Adenovirus


A new lab, with a lot to learn.

I started working in my postdoc lab at the beginning of June, and now I’m finally feeling settled enough to start doing things other than reading research papers.  Ok, admittedly I started a Muay Thai class a month ago (because I’m badass) and I’ve done some painting (because I’m not badass I’m actually an artsy nerdy skinny girl), but I’ve found that creative and physical outlets are extremely important for my mental health as a scientist. Research is so mentally exhausting sometimes, and life is all about balance, right? Especially when you don’t have any friends and the other postdocs are busy with babies or something.

Now that I’ve gotten a better grasp of my new field and the directions of my project, I thought I’d tell you about it.

Adenovirus!

My lab studies adenovirus, which is actually not very different from the virus I worked on in my last lab, polyomavirus. There are different categories of viruses, and these two are small, nonenveloped, DNA viruses – meaning, they have a tiny DNA genome (instead of RNA), and this genome is contained inside a polyhedral shaped “capsid” shell made up of just a few different proteins.

 
I liked the simplicity of this diagram. 

Why would anyone care about adenoviruses?

Well, adenoviruses are important to understand for a number of reasons, the first one being that they can cause illnesses. A common problem they cause is respiratory infection in children, and a different strain of the virus can cause a bad form of pink eye. And like every other pathogen, they can cause a problem for anyone who is immunosuppressed.

Another interesting thing about adenoviruses is that they can be manipulated and used in a helpful way, for gene therapy (where someone with a genetic disease would be treated with virus that had been altered to carry a functional version of the gene causing the disease).

A third interesting way that adenovirus might be helpful is that the virus can be used to kill cancer cells. The idea is that the virus has to selectively kill the cancer cells but not healthy cells, without first being taken out by the immune system.
A virus that kills cancer: the cure that's waiting in the cold  (I just wanted a simple article about the therapy but this piece gives an interesting story)

What am I working on?

My goal in the lab is to get a better idea of the disassembly mechanism of adenovirus. What does that mean? Well, when the virus finds a cell, and then gets inside, its main goal is to replicate and make new viruses. In order to do that, it needs to get its DNA inside the nucleus of the cell. But if you remember, the virus DNA is protected inside a layer of proteins called the capsid, so the virus capsid has to break apart somehow to free the virus DNA. This is not a simple task, because the whole point of the virus capsid is to be very strong and stable so that it can travel from one person to another during transmission and then through their body. So, viruses have evolved to interact with specific features inside the cell to trigger “loosening” of the capsid and subsequent disassembly steps.

Why is it important to understand the virus disassembly process?

Understanding the basic steps of a virus’s life cycle - how it gets into the cell, comes apart, and gets its DNA into the nucleus to replicate - is important for a lot of reasons, even if it may not seem immediately “translatable” to the clinic. One main reason is for discovery of anti-viral drugs, because these are often designed to specifically stop a step in the lifecycle such as disassembly. If the virus capsid can’t come apart, then the virus can’t infect the cell. In terms of gene therapy or cancer therapy, understanding how the virus interacts with the cell is important so we can manipulate the immune response and/or figure out how we can target the therapeutic-virus to specific cells in the body.

Well I think this general overview is good enough for now. I don’t like overwhelming anyone. Including myself. Back to the lab bench! Today I’m looking at how the interactions of adenovirus with its receptor proteins impact its stability, which you can actually look at by just mixing them together….