“Cell sociology”: An interview with Giovanni D'Angelo

Giovani D’Angelo (credit: Alban Kakulya/EPFL)

Giovani D’Angelo (credit: Alban Kakulya/EPFL)

Professor Giovanni D’Angelo recently joined EPFL’s School of Life Sciences, where he directs a lab in the Interschool Institute of Bioengineering (IBI). An expert in lipids, D’Angelo’s previous work looked at how proteins shuttle lipids from one cell membrane to another, and how cells can maintain compartments with different lipid compositions. At EPFL, he plans to take his research to the next level: the single cell and its social life.

Tell us a little about your background. How would you explain your work to a non-scientist?

I am a cell biologist by training and a biochemist, which means I'm interested in cells. I've been focusing in the last fifteen years on cell membranes and the lipids they are made of. Almost every living object is surrounded by a lipid membrane that serves as a defense but also as the very first interface between the living object and the environment to exchange information.

My interest is to understand how cells make produce the lipids that make these membranes. What machineries do they use? And what does it mean for a cell to have one or another membrane lipid composition?

It's like wearing a coat and going out. The coat protects you from the environment but it also communicates about you to others. It can be a uniform, and then people will understand you are, say, a soldier. Or it could be something different, and people will know other things about you. In some sense it influences your social life.

So, what I'm interested in is this interface between the cell and the environment, in the context of protection and in the “social life” of a cell.

What attracted you to EPFL?

I applied to different places where research and teaching are at highest standards, which is the case without any doubt here at EPFL. But it was the emphasis on quantitative biology that finally led me to choose it. So the fact that here I could approach the themes I'm interested in, not in a scripted manner but in a more solid and quantitative manner – that was what really attracted me.

As I'm interested in the “social life” of cells, the strong experience that EPFL has with some model systems where these aspects can be modelled, such as organoids – it's quite unique. That was another plus that attracted me to EPFL in terms of research.

As for teaching, EPFL is one of the best schools in Europe and in the world. Teaching at EPFL is a great honor for me.

What are your current research goals? What do you expect to achieve at EPFL?

At the moment I have a project about the variability of the composition of the membranes of single cells. It is becoming apparent that variations among cells are not just an epiphenomenon of some noise or statistical variance, but that they might have biological meaning.

This has been explored for nucleic acids, DNA and RNA, but much less so for lipids or metabolites in general. Learning about metabolic variability probably will give us more information than we expect. In the context of membrane lipids this is of special interest owning to their importance in cell-cell interaction and in cell signaling. Thus, this is one of the things that I want to develop here, both in terms of technology and of basic research science.

What techniques do you plan to use?

The kind of techniques that I'm going to use are for, 80% standard cell biology and lipid biochemistry techniques. An important thing to mention is that I'm planning to get a MALDI imager, which is a mass spectrometer that images tissue samples, and gives you a description of the molecular content of that tissue or sample in a space-resolved manner. What we would like to do is to take this to the cellular and possibly subcellular level.

What do you foresee for single-cell biology, in terms of medicine or for the life sciences?

Going back to that concept of social life of cells, one clear example of a disturbance of that is cancer. In cancer cells ‘misbehave’. A cancer cell divides or migrates when it shouldn't. This is something that we know is linked to a massive change in the lipid content of cell membranes, and one of the most interesting parts of the research I plan to do at EPFL is about understanding what it takes for a cell to live in a context, and will tell us what is wrong when the cell fails to do so.

Do you foresee your research intersecting with other disciplines at EPFL?

There are some parts of the work I plan to do that will certainly intersect. For instance, in image analysis, where statistics will be central. Advanced image analysis will be key for the success of whatever we try to do.

And then, there is this my dream: some of the lipids I study sit in membranes and have polymerized sugars on them. And these polymerized sugars aren't just linear strings; they have branched structures that are assembled in a not “template-driven” fashion, as we say. So, there isn’t any DNA or RNA that directly codes them, but their production is still very tightly controlled. This suggests that there should be some information linked to these molecules.

In order to understand more about this, it would be very interesting to have a language scientist help us; somebody who can tell us, "A structure like this could be read by this kind of machine, because it belongs to this Chomsky category". And this is something that I will go look for as well.

Are the sugars evolutionary conserved across cells?

It's the fastest-evolved polymer you can think of. Other polymers, such as nucleic acids or peptides show little variation in their constituents among bacteria, archaea and eukaryotes. Glycans have been changing. We, for instance, as deuterostomes – so, vertebrates – use, twelve sugars for glycolipids. Yeasts and plants use three, and they’re not even the same sugars. The complexity of glycan in vertebrates emerged more or less around the Cambrian explosion, when more complex multicellular organisms started populating the planet.

What is your impression of Switzerland so far?

I love it. I come from a beautiful country but having many problems. Switzerland, at least Suisse-Romandie seems to bring all the good things that a southern country has with all the good things that a northern country has.

What are your impressions about Switzerland in relationship to science and research culture?

It's a niche. I mean, in a way it's a bit scary, too, because it's a niche. It's the best place to do science in Europe for many reasons. The conditions people are given here are way better than anywhere else, and this makes you, probably, be in the right position to produce the best science you can produce.