Well it’s been a busy week, I’ve just returned from the 11th world congress on endometriosis in France, where I learnt a lot of new things about endometriosis, met a lot of experts in the field and also had a bit of time to enjoy the Mediterranean weather. I’ll be talking about the conference later, but before that I'm going to wallow in immodesty by talking about my very first proper scientific publication on endometriosis entitled “The emerging role of epigenetics and microRNAs in endometriosis” which was published in the Journal of Expert Reviews of Obstetrics and Gynaecology. You can find a link to the abstract here but unfortunately this isn’t the sort of journal you could go down to your local newsagent and pick up. You may also be slightly disheartened to see that in order to read the full article you have to pay $60 (£30) for the privilege (I hasten to add I don’t receive a penny of that money).
Should you be willing to pay the publisher’s charge then that is all very fine and dandy and I hope you enjoy the drive home to your palace in your gold plated Ferrari. If however, you would like to receive the general gist of the article there is a way to access the information it was based upon which would incur you no extra cost. You see, the article itself is taken from what I wrote in my master’s thesis, so if you could read my master’s thesis, you would have a good idea of what is in my article. Fortunately, my university have started keeping an online repository of all recently submitted theses in an electronic format, including mine, which you can find and download here in PDF format.
However, it would be pretty rude of me to just say “here’s my work, enjoy” then stroll off into the sunset, without putting it in context, particularly because the esoteric nature of scientific literature means it is often inaccessible to the public. It would also be pretty silly of me to dedicate this blog to explaining the scientific work of others without explaining my own, so here goes.
The subject of my work, in this instance, concerns the involvement of epigenetics and microRNAs in endometriosis and how the disease originates and progresses. If you’re reading this then chances are you don’t need me to explain endometriosis, but I’ve had several requests to clarify what are epigenetics and microRNAs. The term ‘epigenetic’ loosely means ‘on top of genetics’, so we should probably explain genetics before we tackle epigenetics.
In broad terms genetics is the study of DNA and the way in which it works. DNA is the universal code for life, some of you may have seem this picture before
That is the structure of the DNA molecule, made from just a handful of different elements joined together in a special arrangement; it is a long list of instructions for making you. Encoded in that double stranded helix is a great deal of information about you; from the colour of your eyes, to the shape of your nose, it dictates the fate of many a feature we use to describe ourselves. Almost every cell in your body contains DNA, and it is a large set of instructions by any account. In total, human DNA contains around 30,000 different individual instructions and each of these instructions we call a ‘gene’. The purpose of most genes is to produce a protein which carries out a specific function. Some of the proteins produced are enzymes that make hormones; others are receptors that allow cells to communicate with one another, the list of functions is quite literally staggering, but all work together to keep your body running. So how do we go from DNA to protein?
Firstly the instructions in the gene have to be read. In order to do this the double strands of the DNA split apart and are transcribed by an enzyme called polymerase. This transcription produces messenger RNA, essentially little pieces of single stranded DNA that contain the information to make a single protein. The messenger RNA then travels to a protein called a ribosome which translates the messenger RNA by bringing in transfer RNAs which have amino acids bound to them. As the transfer RNAs bind to the messenger RNA the chain of amino acids grow longer and as the chain grows it begins to fold into a specific shape that will dictate the function of the protein. Sometimes it is better to visualise these processes as a diagram so below is a picture of the whole transcription and translation process.
An easier way to think about the whole process is to imagine it as a construction site. The gene is like a blueprint to make a house (protein). The information in the blueprint (DNA) is relayed by the foreman (messenger RNA) to the construction workers (transfer RNAs) who, using their building materials (amino acids), build the house (protein).
So where does epigenetics fit into the picture? Well, genetics only tells us what proteins should be made; it doesn’t tell us when they should be made. It is an interesting fact that the DNA in all your cells contains all the genes to make any protein. For example, the cells in your fingers contain the genes to make teeth and the cells in your brain contain the genes to make kidneys. Why is it then, that we don’t have teeth-hands or brain-kidneys? Well this is where epigenetics comes into play. Epigenetic mechanisms are like switches that can turn genes on or off. There are several epigenetic mechanisms, but the ones I have studied most are DNA methylation and microRNAs.
DNA methylation involves sticking methyl groups to DNA which stops the process of transcription; microRNAs on the other hand act by binding to the messenger RNA, either stopping it being read by the ribosome or signalling that the messenger RNA be destroyed. If we go back to our construction site analogy; DNA methylation would be like someone taking a black pen and blanking out all the bits of information on the blueprint that aren’t needed. MicroRNAs would be like lawyers, who stop the foreman and tell him he can no longer build. Epigenetic mechanisms such as these are extremely important for making sure that your cells function properly, any errors in the way these mechanisms work can be disastrous for your body.
I’m hoping my cobbled together explanation of genetics and epigenetics has made at least some sense, but how does it all fit into endometriosis? Well, there have been several studies that suggest that epigenetic mechanisms malfunction in endometriosis. Despite the work of a few pioneering scientists, our understanding of the subject is not complete by any means as epigenetics is a relatively young field of science, having only really existed for the last 20 years or so. Nevertheless, epigenetics has told us a great deal about the way in which complex diseases like cancer work, so the aim of my article was to take what we do know so far and see what it can tell us about some of the mysteries of endometriosis.
I’ll summarise what I wrote about in my paper, and keep it brief for everyone’s sake.
- There are altered patterns of DNA methylation in endometriotic cells that may explain why they are so resistant to drugs and how they can produce their own estrogen supply
- The pattern of microRNAs is different in endometriotic cells compared to normal endometrium, this could explain a number of features of endometriosis, including some of the immune system abnormalities associated with endometriosis
- The altered pattern of microRNAs and DNA methylation could also potentially explain the rare instances when endometriosis of the ovary can turn into ovarian cancer
- Because microRNAs are also found in the blood, the pattern of microRNAs in women with endometriosis may be different from that of disease free women (I found out only last week that this has been experimentally proven). Therefore, this could lead to a simple blood test for endometriosis
- · Epigenetic errors can be brought on by exposure to certain environmental toxicants. These epigenetic errors can be passed down family lines. This means that some pollutant that your mother, or even your grandmother, was exposed to may have increased your risk of developing endometriosis.
I’m currently writing another paper where I hope to expand on the role of epigenetic mechanisms in the malignant transformation of endometriosis. But enough of this self-congratulatory ego-massaging, as I mentioned at the beginning of this post, I’ve just returned from the 11th world congress on endometriosis so for the next few weeks I’ll be putting up ‘mini-posts’ about some of the more interesting things discussed at the conference.