Dear Regina, your two big scientific passions are bones and ageing. How do our bones behave in old age?

To be able to imagine that, I first have to clear up a prejudice about bones. We always think of bones as hard, inanimate tissue, but we only know models from biology lessons or dead bones from museums. Living bone is such a dynamic tissue. It is a constant interplay between bone-forming and bone-degrading cells. Bone mass is built up and repeatedly remodelled, for example in adaptation to changing mechanical requirements. Bones like to be stressed. Plenty of movement shifts the balance towards bone-forming cells.

We reach the highest bone density at around 25, after which it gradually decreases. More bone is degraded than built up. There are more complications with injuries, and fractures heal more slowly. If bone mass is particularly low, for example in osteoporosis, falls from a standing position can end in a bone fracture. The goal of our research is, of course, to help patients of all ages heal better.

What can we learn from animals about regeneration?

A lot! It makes a huge difference whether we study phenomena in the laboratory or in a real body. I worked with stem cells for a long time, and it is totally cool to watch the individual cells grow and mature, but also very artificial. A stem cell cannot be without its niche, its natural home. Every cell is constantly interacting with its environment. We have to look at whole bodies, not just their smallest parts.

Originally, we wanted to work with axolotls. This particular species of salamander is known for its ability to regrow entire limbs. We were thinking about how ageing could influence such regeneration. But then I was talking to a colleague at a conference and he said “Have a look at the mouse, there’s something similar in the mouse!” And indeed, a mouse cannot regrow a whole leg, but it can regenerate its outermost phalanx. And this is, of course, much more exciting for us, because mice as mammals are much more similar to us humans than the axolotl.

Why does this work in mice? What makes them different from us?

I wouldn’t dwell too much on the differences here. If not too much of the fingertip is lost, it can regenerate in humans too. The soft tissue grows back, the nail covers it and often there is hardly any difference from before. In mice, fingertips can also grow back if 50% of the first limb has been lost. They have considerable regeneration abilities which also function in old age. While it takes about a month for the fingertip to be restored in young mice, it takes 1-2 weeks longer in older specimens. The finger bone also grows back; you can literally watch it grow in the computer tomograph.

Bone regrowth has not yet been systematically studied in humans, but there are considerable case studies. A doctor from Sheffield, England, observed and described cases of spontaneous regeneration in young children as early as the 1970s. This was originally a chance discovery, because normally lost finger joints are sewn back on, or the wound is at least covered with a flap of skin. But due to a mistake, a child was once sent home with only a cleaned wound, and when he came back to the hospital for a check-up a few days later, regeneration had already begun. 11 weeks later the phalanx had grown back.

I always ask myself with such regeneration processes: how does the body actually know its outer limits if these have been lost? It’s not as if we give the finger its shape, its curvature. It finds it again all by itself. How does it do that?

The conservative answer would be: We don’t know for sure. But there are clues. For example, there is something called positional information. Cells carry information that is indicative of their position. For instance, fibroblasts, connective tissue cells that are found in many different types of tissue in our body, are particularly rich in this information. Not all fibroblasts are the same. Fibroblasts from the scalp are epigenetically different from those from the toe. They know where they are. And there is the hypothesis that fibroblasts form a system of coordinates in the body that other cells can use for orientation.

Coordinates are a good keyword. I didn’t recognise you as the new group leader during our first meeting, but you stood in front of me, laughed and said “Grias di”, in the best Halleiner dialect, whereas I was expecting a Texan. What brought you to the USA from Austria back then?

Actually, I always liked it at home. But because of all the travelling I did during my doctorate, it became clear to me that I wanted to go abroad to broaden my horizons. That it became the USA was actually a coincidence. I simply followed the research on ageing.

The USA was somewhat ahead of us in this field at that time. The IBA in Innsbruck was the first age-specific institute in Central Europe, and I already knew it from my doctoral thesis. However, I quickly realised that they only put their pants on one leg at a time, too. My lab there didn’t look much different from the one in Innsbruck. What is different is the work culture. You are expected to be available all the time and in the lab as much as possible, even on weekends. That takes the joy out of the work.

And now you’re back – what’s different in Austria than in the US?

If I answer an email on Monday morning, that’s perfectly fine in Austria. It’s very reassuring. As a scientist you don’t get rich, but the freedom to pursue ideas and the joy of work are the big plus. I also like to work at weekends out of my own motivation, it just shouldn’t be a basic requirement.

So you like the research at the LBI Trauma and AUVA?

Yes, and I particularly like the fact that there is a common mission here, a common thread that we all pull together. That is also noticeable in the atmosphere. No one here at the institute wants to be the superstar. That’s often different in the US, and it’s very debilitating when it comes to working together. You have to think carefully about who you trust or who could steal your idea. Here at the LBI, it’s not about who publishes something first, but how we can advance research for accident patients together. That’s the kind of environment you like to work in.