BUILDING BRIDGES BETWEEN CANCER AND AGING

In the following lines, I will try to explain my experience while doing a Short Term Scientific Mission (STSM) with Professor Helen Byrne at the Mathematical Institute, University of Oxford, where you can feel maths everywhere around.

As a headline, I can already state that it has been an incredible ‘adventure’ in many different senses and, without hesitation, I would do it again! If you would like to know a bit more about the research carried out while being there, I encourage you to keep reading 😉

During my PhD, I’ve been focused on studying cell reprogramming, that is, the process that differentiated cells undergo in order to become pluripotent cells (stem cells like). In particular, this process becomes highly interesting when studying cancer, because it could explain the appearance of cancer stem cells, that is, cancer cells that get reprogrammed towards a less differentiated state, from which they can be even more harmful.

The occurrence of the reprogamming process relies on the fact hat differentiation genes should get closed, whereas pluripotency promoting genes should open. The reason why this can happen is related to epigenetics which, among other things, is in charge of removing or adding some marks into the DNA (acetylation and methylation marks, to be more precise). These marks, in turn, are responsible for making a region of the DNA open or closed and thus, able to do transcription or not, respectively.

Before moving to Oxford, with my supervisor (Professor Tomás Alarcón) and the biologist Javier Menéndez, we had been studying and analysing the reprogramming process. In all our modelling, though, we were assuming an abundance of the acetylation and methylation marks in the media, so we were not worried about their evolution with respect to time . Moreover, this is an assumption accepted among biologists because, in general, it happens to be like this. However, when talking with Professor Byrne, we realised that, in fact, incorporating the time evolution of these variables into the model could lead to really interesting insights because, probably, this would take us to consider the most interesting clinical cases.

To be more precise, when we age, it has been shown that the levels of acetylation and methylation marks change and hence, assuming their abundance in the media is no longer a valid assumption. Therefore, in order to cover a larger number of possibilities, we agreed to develop an extension of the previous model. With this new ‘revisited’ version of the model, we can get both limits, that is, the abundance in the media limit (i.e, the model previously built) as well as the limit where the marks are sparse. So, during the STSM, we have been able to develop this more complete yet complex model.

At this point, I would like to highlight the importance of the STSM in all this process because it’s quite likely that, without the scientific discussions with Professor Byrne, we wouldn’t have thought about this other limit. Thus, the STSM has given to my PhD a new direction of research with an interesting idea to explore. It’s also worth mentioning that our biologist collaborator, Javier Menéndez, is highly excited about this new research line which he considers really innovative and he is already waiting for the results.

Now, once the STSM is finished, we expect to continue the collaboration with Professor Byrne and to study the outcomes of the model, as well as possible extensions. For example, we would be interested in coupling this model with some other models or even to some problems observed in pregnancy, which are well-known by Professor Byrne.

Hence, the STSM has been really worthwhile in the sense that it has allowed me to start collaborating with Professor Byrne, to tell her about my research and to jointly agree how to enlarge the applicability of the model, something which is really encouraging and challenging. Not only this, but the STSM has also given me some other features. To mention some of them, I can say that the STSM has offered me the opportunity to stay in a world leading research centre/University, where I have had the chance to enjoy talks and seminars given by experts in the research area I’m researching on, and to present my research to other people working in similar fields so as to get useful ideas. Furthermore, I’ve experienced Oxford from a student point of view, which include entering to some colleges, visiting important buildings such as the Radcliffe Camera or the Bodleian library…

Altogether, I would conclude that the STSM has been a life experience, both from a scientific and a personal point of view.  All the people I’ve met at the Maths Institute, researchers and students, have helped me a lot to make the most of the STSM and have allowed me to grow as a researcher. Therefore, I’m really grateful for this opportunity which I’m sure will help in my future career!

By Nuria Folguera

Nuria Folguera is a PhD student at the CRM

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