Forskarprofilen: Sophie Sanchez

Fleshing out the origins of our muscles

Without advanced musculature the first four-legged animals would not have been able to move onto land. How the interaction between muscles and bones once evolved remains a mystery, one that palaeontologist Sophie Sanchez is determined to solve.

The office at the Department of Organismal Biology gives surprisingly few clues to what Sophie Sanchez spends her days investigating. The shelves feature mostly binders, boxes and piles of paper. However, on her desk are two switched-on computers. One of the screens shows a picture of a bone fragment. A portion of the image is significantly enlarged, revealing round cavities that once contained bone cells. Tracks of what looks like major blood vessels can be seen snaking through the tissue. Details emerge with razor-sharp clarity from different directions as Sophie Sanchez rotates the image.

‘This is a humerus from Eusthenopteron, a fish that lived in Canada 370 million years ago and was a close relative of the so-called tetrapods, the first four-legged animals. We can see the channels where bone marrow was formed, extending from the humerus out towards the other bones of the fin.’

The discovery is not only the first evidence of bone marrow inside fish fins. It also shows the marrow’s involvement in the extension of the fin bone raising the researchers’ hope for answers to how limbs once evolved. The bone marrow is also behind key features such as the formation of new blood cells thus affecting blood circulation and regulation of the immune system.

‘We know that bone marrow has played an important role in the growth of bones of land vertebrates and that the marrow is mainly located in the arms and legs. However, it is a long time since we emerged from water, and during that time the shape and characteristics of all our bones have changed. It’s no longer possible to see where in our bones the marrow developed,’ says Sophie Sanchez.

‘But if we return to our origins when the structure was simpler, we can find more precise answers. If there’s then a problem with bone marrow, we know where we shall focus. This knowledge may be very useful to understand the bone marrow from a biomedical point of view.’

The Eusthenopteron findings were published in 2014 as a result of a collaboration between researchers at Uppsala University and the European Synchotron Radiation Facility, ESRF, in France. It is one of the Europe's largest facility for the production of synchrotron light for palaeontological uses. The intense and powerful beam produced by high energy electrons passes through the bones of fossils, allowing scientists to explore the internal structures such as cell or blood-vessel cavities and bone density. Special camera optics attached to the beams provide a resolution of up to 0.7 microns, or 0.7 millionths of a metre. The instrumentation creates three-dimensional images, making it possible to analyze a fossil without cutting the material.

‘The organisms we’re studying have been fossilized for such a long time that they’ve become as solid as stone’, says Sophie Sanchez. ‘But with the synchrotron light we get submicron resolutions of all kinds of structures. I'm mainly interested in the cavities of the bone where the muscle fibers have been attached. And for the first time, we’ve been able to locate precisely where a muscle was located on the 370-million-year-old fish Eusthenopteron.’

Despite the many benefits of synchrotron light, it has proven difficult to distinguish the smallest components of bone mineral known as apatite crystals without slicing the bone in pieces and destroying the material. Together with European palaeontologists and synchrotron physicists, Sophie Sanchez is working on the development of the synchrotron light technique in order to study the bone structure of fossils in even greater detail.

‘We hope to soon to be able to perform new experiments to obtain the information we need. How did these animals move and lives? And how did they acquire the possibility to get out of water? We want to understand the transition from fish to four-legged animals, which of course is about our own origin.’

It was during her doctoral studies in biology that she became absorbed by the fin-limb development, and the evolutionary step onto land. Sophie Sanchez was studying at the Natural History Museum in Paris when she one day encountered Per Ahlberg, a Professor of Evolutionary Organismal Biology at Uppsala University. Shortly thereafter, she contacted him to propose a joint research project.

‘I asked him and palaeontologist Jenny Clack from Cambridge if they would be interested in me looking at the bone histology of early four-legged animals. No one else had done it before so nobody knew anything about the physiology or life history of these crucial fossils. I suggested that we could do some experiments at the synchrotron facility in France to avoid damaging the samples. When the results later proved very promising, I came to Uppsala in 2009 and started as a post-doc with Per Ahlberg.’

Today, Sophie Sanchez leads her own research group consisting of two doctoral students, one post-doc and a master student. She is also responsible for the master course Evolution and Development and is involved in three additional courses. She hopes her passion for research will motivate her students to feel the same way.

‘When I teach, I want the students to get involved, ask questions and desire to learn more. I think new technologies can be of great help. An example is the scanning electron microscope that I use in a course on plant structures. It’s a very advanced tool that keeps students active and encourages interaction, something I think helps them recall what they’ve learned. Also, they get to try the technology used in real research projects.’

With all the teaching, she has got less time for her own research these days, which she sometimes misses.

‘I think it's really exciting to be a researcher and go out in the field, collect samples, prepare them, do experiments and compile information. Of course, you also need to have a lot of patience and motivation, but when you finally get your results it’s worth all the hard work.’

There is no doubt about her major goal.

‘To be able to reconstruct the muscles of these extinct four-legged animals would be a dream come true for me. If I could succeed, it would be absolutely fantastic.’

Anneli Björkman