New Blog Site!

My computer-savvy friend Youn told me I should switch to Wordpress, so I have set up a new site here, with all my stuff and new posts: 

"Membrane Penetration"

Let me know what you think!

....

This is Youn's photo of his puppy and I think she should be everyone's spirit animal.

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. 

Source of image

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.

CDC: adenovirus

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).

Retooling for human gene therapy: new and improved adenoviral vectors

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….

Sorry, I've been busy, but I wanted to post an update at least.

I successfully defended my PhD!

I got a gold star. ;-)

I have a job!
I will be doing a post-doc with Glen Nemerow at the Scripps Research Institute in La Jolla, CA. Working on adenovirus.

Look how cute it is! It wants a hug.

More updates and sciencey posts soon, I promise.

My Dissertation (Intracellular trafficking of BK Virus: from the ER to the nucleus)

So, I set a date to do my thesis defense, on December 13. This means I have until the end of November to submit my dissertation to my committee… which means, I should be working on it right now. Instead, I thought I would try to explain my work here where I don’t have to use big words all the time.

The BK Virus (Signficance)

The lab that I work in does research on BK Polyomavirus. The BK does not stand for anything. Would it really matter if it did? Call it the Burger King virus like my family does. Anyway, “BK” is a virus that is actually already inside 90% of people because we pick it up when we are dirty kids. But that doesn’t matter, because healthy people aren’t really affected by the virus and it just hangs out quietly throughout your life. That means it’s actually very good at being a virus because it is able to quietly spread through the population without making a mess… that’s a conversation for another time, though.

Why do we study this virus? We get funding to study this virus because it can cause problems for people on immunosuppression, especially people with kidney transplants. When the immune system is taken out of the picture, the virus gets out of control replicating in the kidney cells and can basically destroy the new kidney. 

Importantly, we don’t have any anti-viral treatments for BK. This is partly because there a lot things we do not know about how the virus works. That’s where I come in! And other researchers.

My Research (Introduction)

The way that anti-virals work is they usually block a process in the virus life cycle.  There are a lot of different things that need to be known about cells and the virus and how they interact if you are going to make a drug that gets in the way. So, basically my goal is to understand how the BK virus interacts with the cells. I am doing that by figuring out how it travels (or “traffics”) through the cell. I am not looking specifically for a cure for BK infection, but I am learning all about how the virus uses and messes up normal cell biology. Then, someone else can use that information to make informed decisions about what drugs might stop BK.

How do we figure this stuff out? (Materials and Methods)

Basically, I work with human kidney cells in a petri dish, and I infect them with virus. All you have to do is put some pure virus on top of the cells, they will become infected. I can tell they are infected by looking for a certain virus protein after a day or two. So, to answer my question of what the virus interacts with inside the cell, the main way to do that is to take away certain things in the cell, and see whether they can still be infected, and what is happening if they can’t be infected. Interestingly, the cell can still function pretty well without specific proteins or pathways.

We can take away cellular functions in a few different ways. The method I’ve used most often is I treat the cells with a drug that specifically stops certain proteins and cellular machinery from working. These types of drugs are often only used in research to help figure things out. They are super convenient.

What did I find? (Results)

Do you remember high school cell biology? What I found is that BK travels from the outside of the cell, into the endoplasmic reticulum (the ER), then into the cytosol by using something call the proteasome and ER-associated degradation pathway, and gets into the nucleus by using the nuclear pore. I’ve illustrated it below.

At this point you might be like, gosh who cares?! This is boring. Well, shut up. Its super cool that a virus can go from outside your body to inside your body and then inside your cells and then travel through the cell and disassemble and put its own DNA into the nucleus of your cells and replicate. Watch the Battlefield Cell video!

What does all this work I did contribute to science? (Discussion)

The goal of scientific research is obviously to contribute to science by providing information that was not known before. My research hasn’t been super ground-breaking, because we had hypothesized that these things were true based on work that had been done with similar viruses, and then gave evidence that they were true. But that’s what a lot of science involves, just supporting hypotheses that are out there but haven’t been given much "convincing" evidence yet. My hard work has contributed to the field of virus research, whether it was earth-shattering or not, because it has provided data that did not exist before.

What helped me finish grad school? (Acknowledgments)

I would like to acknowledge these things that have been with me through these past five years:

anti-anxiety meds, alcohol, cardio workouts, cookies, things that remind me why I love science, beer, friends that make me laugh, realizing that I can still be called a scientist after failing, people who tell me I’m smart.

How to work with Ebola virus.

I have a thing for science, obviously, but viruses are my ultimate love. It's the field in which I am working toward my PhD (and hopefully will receive in the next few months). Related to this, I follow an awesome virology blog and podcast put on by Dr. Vincent Racaniello. I highly recommend these resources because they are meant to be useful for non-scientists.

Anyway, I just wanted to share a cool thing they did, which was to create a documentary about a biosafety-level 4 (the highest there is) facility and what it is like to work there.

See the trailer first:

Then watch the documentary! ...through their blog or through microbeworld.

Aaaaand then read The Hot Zone to have your mind blown by virus awesomeness.

Animations are the best.

This is one of the best cell biology animations that I've ever seen. It's exciting and detailed and shows why studying viruses is a good way to understand basic cell biology! My younger brother thought it was sweet so that's a good sign for you. 

Watch Curiosity: Battlefield Cell.

 

It seems to be from a discovery series called Curiosity. I don't have cable soo thank goodness for the internets.

I really think animations like this are a great way to understand complex systems like a cell, where there are a lot of things happening in three dimensions.  I guess I was already pretty excited by cell biology from studying the normal books in high school, but if I had seen this, I probably would have peed myself.

Hey ya'll.

A flask with candy in it. Because it was cute?