What is melanoma and how does it occur? Melanoma is a cancer that occurs in the cells responsible for the colour of your skin. Like other cancers, melanoma can be considered a genetic disease, that is, it’s the accumulation of mutations in DNA that cause the  the disease. In regards to melanoma, the majority of these DNA mutations occur from ultraviolet (UV) radiation exposure from the sun.

Significance of melanoma: Melanoma accounts for nearly all skin cancer related deaths; in 2009, approxiamately 2100 people died from melanoma in the UK . Melanoma is dangerous because once it spreads to other parts of the body (metastasis), traditional cancer drugs such as chemotherapy are ineffective. There has been a significant need to develop new drugs that are effective in treating metastatic melanoma. Everyone has to be careful as melanoma can affect people of all ages, including young adults.

Why find DNA mutations that cause melanoma? If we can find the mutations occurring in DNA that cause melanoma, we can use this information to develop new drugs in treating the disease. To summarise that in 4 words: Find mutations- Develop Drugs. Last year (2011) we had some tremendous breakthroughs in the treatment of melanoma with the approval of 2 new drugs, the first in 20 years, and of which are beginning to make an impact on overall survival. One of these drugs, Vemurafenib (also known as PLX4032 or Zelboraf), is an example of a molecularly based targeted drug and targets a mutation in a gene called BRAF (known as a V600E mutation, this mutation occurs in about 50% of melanoma patients). This type of drug is designed to counteract the effect of overactive cell signalling produced by mutated genes that cause cancer.  The success of these new drugs started from the initial discovery of mutations causing cancer and is why finding these mutations is important.

Vemurafenib (PLX4032) is a drug that is effective in melanoma patients with a specific mutation in a specific gene (BRAF V600E) and occurs in about 50% of patients. Although the drug can reduce the size of tumours, for some patients the tumours can grow back. As such, we need to continue to understand how melanoma occurs so that we can improve the drugs we currently have or make new ones that will treat metastatic melanoma.

How do you find mutations in DNA? Basically we use a variety of sequencing machines. Over the last couple of years there has been a big increase in the power of sequencing technology that has allowed researchers to do experiments that previously, would have been too expensive or too time consuming to do. To give you an idea- the first complete sequence of a human’s DNA (or genome) cost approxiamately $3,000,000,000 and took 13 years to complete (look up the Human Genome Project). You can now sequence a human genome for ~ $4,000 in a matter of weeks! One sequencing company stated in February this year that by 2013 they will be able to sequence a genome in 15mins!! (see Oxford Nanopore). Because sequencing genomes are cheap, we can now use this technology to sequence cancers (or tumours). This allows us to quickly find all the mutations that have occured within a patients tumour, helping us to understand how the cancer occurs and potentially allowing us to make new drugs or improve existing drugs.  Even more exciting is that this sequencing technology is beginning to be used within the clinic  for people who have cancer (i.e. at the doctors and hospital). Based on the mutations that are present within your tumour, the most likely drugs to be effective for your specific cancer can be used as a treatment strategy. This is a concept known as “personalised medicine”.

Examples of sequencing machines. Perhaps by the end of the year sequencing can be performed on a machine the size of a USB stick

I actually spend a fair bit of time on the computer. This is because the sequencing technologies that I use generate heaps of data (and I mean HEAPS of data). It can often take a while to sort out the data and find good mutations and genes to follow up; sometimes it is a daunting task but the challenge is part of the fun.  Also, there is nothing quite like stumbling across a cool new direction after hours of sifting through data.

When I am not playing around with data I am usually reading about all the research that other groups are doing around the world, both within and outside the field of melanoma.  Although it can take up a fair bit of a time I think it’s worth it in the long run.  By doing this you know exactly what has been done before (so you don’t waste time working on something that has already been discovered). For me it also generates new ideas that I can use to tackle interesting problems that haven’t been answered yet in regards to melanoma.

Me in the lab next to one of our sequencing machines

Writing is the next big thing. Science is all about publishing your results and getting your discoveries out there.  During times when I need to write I find that working late at night is best for me- no distractions. As a consequence my typical day doesn’t kick off until about midday. I do have the option to do some writing at home but that never works- particularly during summer season when the cricket is on! This is another good thing about being in science, you can have flexibility in your work hours.

I live in Brisbane Australia and have more or less lived their my entire life. I am completing my PhD at the Queensland Institute of Medical Research (QIMR) and probably would have just submitted my thesis as you read this. QIMR is a fantastic institute that researches a variety of important topics including cancer, complex disorders and infectious diseases such as malaria.

Our institute is made up of three buildings. I work in the Clive Berghofer Cancer Research Centre (featured bottom)

Yes, you read correctly. I have this great idea for an experiment that details the basic principles of mutation detection that could be easily performed by students within a couple of hours. Stay with me for a minute and read on…

Did you know people have two types of earwax? Yes, they do. If you’re game, why not do an experiment and prove it for yourself by sticking your finger in people’s ears (just make sure you ask permission first!).  The majority of people have a wet form of ear wax (that’s me), but there is also a dry form as well. A large factor that determines your earwax type is your ancestral background.

People have two types of earwax- what type is yours?

What causes the different types of earwax? Nearly all variation of earwax type is determined by a single base pair change in your DNA! This is due to a single nucleotide polymorphism (SNP) known as rs17822931. People who have wet earwax have a genotype CC or CT while those with dry earwax have TT (remember we have two copies of DNA in our cells, one copy from our father and one from our mother)

The principles and learning objectives behind the project. The idea is to create a quick, cheap and easy to follow science demonstration experiment that could be used to determine a person’s earwax which doesn’t use expensive equipment. Through this process you learn how to extract DNA to identify a variation (genotype) that results in a change of appearance (phenotype). This process can then be compared to what I do for my research which is identifying mutations (or variations) in DNA that cause melanoma. Normally this process would take a day or two to perform; this is too long an experiment for most students who visit the lab. As such, it would be great to have a similar experiment that could be performed in a couple of hours.

What the money would go towards. If I won the money, I would use it to develop a 2 hour experiment that determines a person’s type of ear wax through a colour change reaction. I have wanted to do this for a while but have needed some initial funds (and time) to see if I can get it going. As with all science experiments, there are no guarantees that I could achieve this goal; however, there are published methods suggesting that this is possible. If I manage to develop the experiment I will publish it online so that anyone can do it- it will be a valuable resource for others who want to demonstrate how variations in DNA can be detected. I will also use the method in my future science demonstration and communication endeavours.

I wonder what type of earwax our Australian ex-prime minister Kevin Rudd has (Check out the clip below)

mmm… What type of earwax do you think he has?