Tuesday, January 14, 2014

So what is it you do as a 'scientist' anyway?

Surprisingly, explaining the evolution of my fairly infantile career and even my current job can sometimes be a bit of a challenge. I mean how does someone go from forensic science to neurogenetics? Why do you get all excited? And are lab coats really comfortable (A: yes, yes, they are.)

I think if I have to define my job, I'd probably say I'm a molecular biologist who has a big focus on methods to analyse genetic data. Some may think this relates to engineering super-viruses a la 28 days later, or building Frankenstein. Really, it's a tad less cinematic and involves working on things that are mostly invisible,  appearing as clear liquids that are generally in really small tubes!

Over on everyone's favourite social network site, my current job title is "voodoo HiSeq operator". A bit of a joke, yes, as there's no actual rituals involving snakes and Haitian zombies in my workplace.  But sometimes, science can feel more like art and magic.  Mastering molecular biology sometimes does involve a little magic, hence the job title. But jokes aside:

What's a HiSeq?

And what do you all do day that involves it (plus the occasional bit of voodoo)?

Simply, a HiSeq2000 is a large white box:

Doesn't look like much, and most of it is actually fridge space.

But it's what this seemingly inert box is capable of that is mind blowing.

A decade ago, it took 10 years to sequence a single human genome. Clearly to study the complex world that was unfolding at the genetic level, a revolution of the method to crunch genomes was needed.

And this revolution came in the form of Next Generation Sequencing (NGS). Essentially, by combining some really neat and well known molecular biology with high powered optics and imaging, instead of sequencing single, small fragments of DNA one by one with a maximum of a few hundred fragments every 8 hours or so, we were able to start sequencing millions of fragments of DNA simultaneously.

And that's where the HiSeq comes in. For around $800,000 a lab can buy one of these machines from a company called illumina and can hold the proverbial keys to the genetic kingdom in a small room.  
To give you an idea - the HiSeq has the ability to output the equivalent of 100 human genomes every 10 days. That's 100x what took 10 years a decade ago. Oh, and instead of costing over a billion dollars for a single genome, it now costs a few thousand dollars. Labs around the world have now sequenced birds, fish, plants, microbes and even extinct creatures.

So why have one of these lovely white boxes?

It's nice to generate lots of data.  Data is like crack for a scientist. We're addicted to it, it gets us high and we always want more. The better the data, the more we like it (the come down from bad data is just horrible though!).

But you should have a reason to make the investment. Generating lots of data still costs a lot of money and takes a lot of time. Having shiny new toys is great, but they should serve a purpose.

Aside from making genomic data easy and cheaper to generate, the biggest advantage of a platform such as the HiSeq is it enables the ability to study lots of individuals at an unprecedented level of detail.  

And that's where I come in. Welcome to my world:

The office aka. thinking/emailing/mulling over results space. Note: it is not always this neat.

The bench. Always this neat.

The lab. Sometimes neat, sometimes like a bomb hit it. Usually related to the amount of work going on and how many deadlines there are coming up.

I run a small genetics lab which has huge data generation capability. The focus for me is on providing genetic analysis both of DNA and RNA (the transcriptome aka. protein coding part of the genome)  using the HiSeq and similar technologies to researchers within a large neuroscience institute (and a few external projects). My research background is based in methods and technology, and I think the methods we use is my favourite thing about science. The challenge of getting from A to B,  designing experiments and generating data to answer riddles is basically my job description and what I love most - methods  underpin the answering of all scientific questions. I'm fortunate to get to work quite collaboratively, do a little of my own research and in some cases, push the boundaries and generate data that even a year ago, just wasn't possible. 

Not much bigger than a microscope slide, yet containing 1.5 billion DNA fragments ready for sequencing, this small piece of glass with 8 channels known as a flowcell. A few years ago, a single human genome took 10 years and hundreds of people. Now the same can be done in 10 days, by a single person using this technology.

Data generation in action. The coloured dots are DNA!!

I've worked on everything from sequencing large numbers of individuals to uncover rare variants associated with complex disorders to studying genetic differences in single cells. I work on samples from humans, mice, and bees. Seeing such cutting edge in technology used to unravel and answer scientific questions is just awesome, there's no doubt about it - I should note the disclaimer here: it can be a lot of work. 

I mentioned neurogenetics earlier - all this genetic data I work on generating is related to neuroscience. Think questions around how genes regulate brain development, mutations associated with motor neurone disease, the genetic basis of autism or schizophrenia and studying gene expression in learning and memory formation (just to name a few). Understanding  the nervous system is a very large and complex undertaking, with some biologists even considering it the last major frontier of biology and medical science. It is so large the U.S government is undertaking a project involving large collaborative effort to map the brain, and part of this is genetic analysis of the of the brain. 

Whether applied to neuroscience, forensic identification, evolutionary biology, medical genetics or environmental science, the technology I work with daily has revolutionised just how we study the very code for life. 

Added bonus of my job: some of the reagents I work with are pretty. 

The methods we currently use in research are also enabling the next generation in medicine and fieldwork.  Gradually this same technology is being applied to accurately diagnose the genetic basis of a disease, monitor response to medication, rapidly identify biological material and the field or confirm the identification of an individual using DNA. The era of personalised medicine and use of genetics in the field is actually on our doorstep. 

The most amazing thing for me is, the more we seem to uncover about why we differ, how we evolved, or what is happening in disease, the more complex and wonderful the genetic world seems to become. It's certainly the genomic age, and a great time to be a geneticist. We've certainly got a lot of work to do, and hopefully the technology enables us to continue pushing the boundaries and understanding the code of life, and just how it works to produce everything from bacteria to humans. 

So there you have it, that's my workplace and my job. DNA, RNA, lots of methods and a cool piece of technology that has turned genetics on its head and allowed geneticists to think big and detailed. 

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