Digesting worms

Catriona Crombie, Wellcome Trust Sanger Institute
United Kingdom

I work as a postdoctoral researcher at The Wellcome Trust Sanger Institute, which is based on the Wellcome Trust Genome Campus in rural Cambridgeshire. The alarm goes off as usual at 7 o’clock. I have to stop and feed the horses on the way into work. The field where they live is very close to the Sanger Institute, so it doesn’t add much time to my commute. Once there are five well-fed and happy horses, I get changed and head into work.

The first thing I do on arrival is to check and answer my e-mail. I then write a plan of the tasks I need to do in the lab today. I work in a lab interested in mapping cellular signalling network through large scale systematic methods. We use a nematode worm, Caenorhabditis Elegans, as a model system to do this. My project is specifically interested in some of the genes that are involved in cancer development. I have carried out a number of genetic screens in the worm.

Using RNAi -- a method of specifically knocking down the expression of any gene – we can do this for nearly all the genes in the worm genome. I have identified a number of candidate genes, and now I am trying to back up what we have done by replicating the results in worms that carry mutations in the genes I am interested in. I am trying to cross two strains of worm to give worms that carry mutations in both the genes I am investigating.

I need a way of telling whether or not a worm has the mutations that I seek. So I do a PCR – a method of making lots of copies of a specific bit of DNA -- for one of the genes I want to see which worms carry the mutation. Before I can do the PCR reaction, I need the DNA from the worm. I get this by digesting the worm away with an enzyme called proteinase K.

I set this reaction up and leave the worms to digest over lunchtime. Wednesdays are Rugby training day. I play in the Genome Campus Touch Rugby Team, and we train every Wednesday at lunchtime. When I get back from training, the Proteinase K digestion is complete, and I am left with no worms, just their DNA. I then use this DNA to set up the PCR reaction.

We have a number of groups that all work with ‘model organisms,’ such as yeast and fish. So every week, we have a meeting attended by all those who work with a model organism. I leave the reaction that I started while I go to the meeting. Today, two people are presenting their work. Andy from our lab talks about some his efforts with microarrays. Richard from one of the zebrafish labs talked about work with a fish model for muscular dystrophy.

When the meeting is over, I go back to pour a gel. To see the DNA from my PCR reaction, I separate out pieces of DNA of different sizes in a gel. I then visualise them with a chemical called ethidium bromide, which binds to DNA and fluoresces under UV light. I set my gel up and leave it to run.

We have recently had two new lab groups move in to share the space that we already share with four other groups. So, while my gel is running, I chat to people from the other groups to negotiate on how we can streamline use of the equipment we have and the waste that we generate. I also check that all my stock of worms have enough food and are growing happily. I then look at the result of the PCR reaction on my gel and take a picture of it. It looks good. I write up what I have done today and go home.

I have always had an interest in how things work, whether they were biological or mechanical things. At school, I found that I did well at the scientific subjects and maths. So studying science at degree level seemed a very natural route to take. Later in my degree program, I specialised in biochemistry. In doing my own research project, I discovered that finding the answers to the questions you have set out to investigate is very rewarding. I still have a real passion for the science that I do and very much enjoy sharing that with others.





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