Manuel Llinás: "We need new approaches, new tools, and new ways of thinking about malaria"

Dr. Manuel Llinás is an Associate Professor of Molecular Biology and a member of the Lewis-Sigler Institute for Integrative Genomics at Princeton University. Since July 2012, he has been on sabbatical from Princeton and is currently visiting professor at CRESIB, the research arm of ISGlobal. We asked him about the reasons for this visit, his malaria research and the financial crisis.

Q: You have a Ph.D. in molecular and cell biology from the University of California-Berkeley. Why did you choose biology, and how did you end up in the field of malaria?

I studied chemistry as an undergraduate and I was very interested in the biological side of it. But I didn't feel that I was getting close to being able to have an impact on human health so when I did my Ph.D. I looked for a big biology programme that would allow me to do many different things. The last two years of my Ph.D. I worked on a project with Stanley Prusiner (who went on to win the Nobel Prize for his prion research), a very nice project that got me into human health.

But the real jump to malaria was during my postdoctoral studies. Genomics was becoming a big thing; microarrays were a brand new technique and I went to a lab that did that. After I had been there for a year, another postdoc who knew a lot about malaria joined and that completely changed everything I did from that moment on. I ended up in this field by chance. I was surprised how little we knew about a disease that has been around humans longer than any other disease we have on record. The more I read the literature, the more I realised that the field really needed to be pushed forward with technology, that it was a bit behind the times, even though malaria is probably one of the most investigated human diseases of all time. I thought, "That's where I can make the biggest impact."


Q: At present, you are taking a six-month sabbatical to work at CRESIB as visiting professor. What made you exchange Princeton for CRESIB? What do you think you can contribute to this centre and vice versa?

Princeton is a small university without a medical school. I am the only parasitologist there and, although I have a large amount of support with regard to technology, I miss the connection to field research and to groups that are thinking everyday about malaria. CRESIB is clearly one of the dominant groups in the field and very well recognised internationally. There's a lot of expertise here that I don't have at Princeton.

Besides, I don't do any work on Plasmodium vivax and there are people here working on P. vivax. I think it's important for those of us who work in Plasmodium falciparum to see how our work translates to the other Plasmodium species, because ultimately the challenge is not to fight one parasite, but to fight them all.

Q: In the area of biology, your research is focused on malaria. More precisely, you study the deadliest of the four human Plasmodium parasites responsible for the disease—Plasmodium falciparum. Why is this parasite such a complicated enemy?

These organisms have figured out a way to coevolve and to adapt to our bodies in a way that ensures they do not kill us. This makes them very difficult to work with, because in many ways they have to resemble our own metabolism and physiology to survive within our cells. For a long time, the biggest challenge was the inability to culture. Now that we can culture these organisms we can ask many interesting questions. But the biggest challenge that remains is the bridge between in vitro and in vivo studies. There are clearly things that happen in a flask that don't happen in people. There is a lot we don't understand there.

Despite the fact that it has only 5,400 genes, P. falciparum has an incredibly complex biology. It is fascinating how this parasite has the diversity to be able to live in liver cells, in blood cells, in mosquitoes, to change from being motile to non motile, to go through sexual and asexual stages. In fact, we only understand a small fraction of this organism's biology. I view that as a tremendous opportunity. The challenge is that we need new approaches, new tools, and new ways of thinking about an old problem. It is hard to do that.

Q: What impact do you think your research can have on the fight against malaria?  

People have already found many drugs that kill parasites, but we still have no idea how they work. To me that's fascinating. We have a mechanism of action that we don't understand so we need to come at this from both sides. We need to develop drugs and we need to figure out how those drugs work, what they are targeting. And we have to make sure that the two are optimized to make the next generation of antimalarial drugs.

My work doesn't necessarily focus on vaccines per se, but I have a lot of drug target ideas. That is where our research is focused—on targeting metabolism.

Q: As you probably know, the current financial crisis has deeply affected Spanish and Catalan research projects, which have seen dramatic reductions in their budgets. What are your thoughts on that problem?

The financial crisis is affecting research budgets pretty much everywhere in the world and the problem is clearly worse here. The fact that people don't get all the funding they need to support their work has led us to shift our strategy a bit. We need to think harder about the kind of research we want to get funded and to understand that the pot of money is clearly smaller. In the long run, the best way will be to work together with other people, i.e. to combine our individual expertise on a particular problem, such as malaria.

The positive side of the crisis is that I do feel that now only the best research gets funded. It's a hard way of viewing it, but on the other hand there are a lot of things that scientists are trained to do and we can contribute to society in many other ways. A Ph.D. in science provides you with keen thought processes and a rigorous training that allows you to do many other things in life.