AcademiaNet: Your research at Cardiff University looks at tiny biological molecules called lipids. What are lipids, and what are their most common roles in the body?
Valerie O’Donnell: ‘Lipids’ is just another word for fats. Our body is made up of large amounts of these molecules: most organs are about 30 percent lipids, and the brain is actually 60 percent lipids.
There are three main functions for lipids in our bodies. The first is a structural one: all cell membranes are made of lipids, so they quite literally hold our cells together. Secondly, cells use particular types of lipids - such as prostaglandins - to signal to and communicate with each other. This is particularly important in inflammation. Their third role is as a type of energy storage. If we take in too many calories, we convert them into lipids. The molecules then become part of our adipose tissue. When we need an energy boost, our body can break down stored lipids and use them as fuel source.
You and your team have looked specifically at lipids made by blood cells called platelets, which are responsible for helping the blood to clot in response to injury. What is the role of lipids in this process?
Platelets release a signalling lipid called thromboxane. That, in turn, causes blood pressure to go up and blood vessels constrict. It also causes platelets to stick together, and it activates white blood cells. Aspirin works by blocking thromboxane from being formed by platelets, which means it is anti-inflammatory and simultaneously capable of stopping clots from developing.
You have done some really interesting work on how this response to aspirin varies in different people. Can you tell me a bit more about this process?
We’ve looked not just at thromboxane signalling, but also at many lipids made by platelets. Some of these are new lipids that were identified in Cardiff. Originally we analysed biological responses to aspirin in only three people. There were similarities in how their platelets reacted; for example, thromboxane was blocked in all of them. But also there were also a number of other lipids that were partially blocked or not blocked at all; in some cases, lipid levels even went up. These more subtle responses differed in our three study participants.
With the help of funding from the British Heart Foundation, we’ve started looking at aspirin responses in a much bigger group of about 30 people. We’re looking at how different people react to the drug, and also how stable that response is within the same individuals at different times. We’re still at a very early stage of understanding the diversity of responses we see. Frankly, we are just beginning to investigate which of the lipids produced could be involved in inflammation. We don’t really know yet what the fluctuation in lipid levels means in terms of people’s risk of having cardiovascular disease.
You mentioned that you and your team have discovered brand new lipids at Cardiff. You use very high tech mass spectrometry techniques to search out new lipids – is that right?
Yes, we’ve found well over a hundred lipids in platelets now - this project was funded by the European Research Council. Once we find new lipids, we do in-depth chemical studies on them to work out their structures and functions. The lipids we’ve discovered in platelets and white blood cells come from the same families, so they have similar structures. We think that they’re involved in promoting blood clotting - we’ve got some very good evidence of that in human studies and animal studies, which we’re publishing at the moment.
You have teamed up with University of Cambridge and University of California San Diego to create a database of all the lipids you discover. Can you tell me a bit more about this project?
LIPID MAPS is a database that has been created in 2003. It’s a big resource for the lipid community; there are about 77 000 unique visits to the website every year. It has users from almost every country in the world. Last year, along with the researchers who developed the database over the past years as well as the director of the Babraham Research Institute at Cambridge, I was delighted to secure five additionaly years of funding for LIPID MAPS from the Wellcome Trust.
We’re now working hard on updating the database. There are a number of lipids that have been discovered in the past few years, so we’re going through all the literature to get that information. In the end, we want to include all new data to make them available to the whole community. We also aim to work closely with the lipid biologists and chemists to find out what kinds of new software tools and informatics resources they want on the site. It’s quite an exciting thing, and very different to the research that I do!
Currently you are the Co-Director of the Systems Immunity Research Institute at Cardiff University, which opened in 2015. The Institute takes a quite particular approach to handling large datasets – can you tell me what is unique about it?
In science, or methods are constantly evolving. This also means that we generate more and more data. Some new techniques or analyses lead to the generation of huge datasets, which have to be curated and analysed. In our institute, we wanted to have informatics, statistics and mathematical modelling embedded more in the training of our scientists, to enable them to better handle that data.
For this reason, we send all of our PhD students on programming and database mining courses - to get them up to speed on the statistics tools that they need to work with large datasets. It’s a very fast moving area right now, so we just felt that it was something that we really needed to provide as a resource.
Interview by Helen Jaques for AcademiaNet.(© AcademiaNet)