Author: Eleanor Sheekey
Dr Jean-Léon Maître is a group leader in the Genetics and Developmental Biology unit at Institute Curie in Paris, one of the leading medical and biophysical research centres in the world. Dr Maître earned his PhD at the Max Planck Institute for Cell Biology and Genetics in Germany, and the Institute of Science and Technology in Austria. He furthered his studies at the European Molecular Laboratory, Germany, where he completed his Postdoc. Dr Maître recently published an article in Nature which elucidates how cells in a mouse blastocyst differentiate to become either placenta or embryo tissue (1).
JYI: Developmental biologists focus on the transition from initial fertilisation to the formation of a fully functioning adult organism. What made you interested in becoming a developmental biologist – was it a decision that you made from an early age?
I studied cell biology at university and was interested in developmental biology right away. The coolest thing is definitely to watch embryonic development happening in front of your eyes. There are quite a few videos online, and they are definitely worth watching. I asked one of our lecturers to help me find a lab to spend my 21st summer and very luckily ended up in the lab of Alfonso Martinez Arias, who is very passionate about his research which at that time was on fly development. He was really great at sharing his passion and taught me many stories about the life of embryologists. He then guided my choices when it came to find a lab to do my PhD. I was extremely lucky that he decided to help me.
JYI: What did you choose to focus your PhD on?
So, I joined the lab of Carl-Philipp Heisenberg in Dresden to do my PhD. I wanted to make pretty movies of migrating cells and that is exactly what he was known for. When I joined, the lab was taking a very important turn towards biophysics under the influence of neighbouring labs such as the one of Ewa Paluch and Frank Jülicher. During the 5 years that I took to complete my PhD, the mechanical aspects of zebrafish development became the major topic of the lab. I would say it was the most exciting project I have ever worked on and was once more very lucky to join the lab at that time. It was a lot of fun to be part of this research and to see the birth and shaping of the really fascinating stories that came out from it. In addition, I can apply what I have learnt during my time there to what I am doing now.
JYI: Your latest paper was published in Nature. How does it feel to get published and would you consider it the best aspect of your job?
No, it is very painful! Publishing itself is very important because you want your science to get out of the lab, but the whole procedure is very unnecessarily painful. It is complicated but you need to do it this way because afterwards it makes life easier. Getting your work published in a journal is exciting as it provides motivation for increased publishing but also creates money which can be used for further research.
JYI: Your paper looks at early mammalian development and how contractility, polarity, and position of a cell determines its identity and how they interact – what made your team look at this specifically?
So the good thing about studying development biology is that you can study what you like, including cellular biology, genetics, regular biology, or biophysics. I focus on cellular biology and biophysics. Upon looking at what controls the physics and cellular processes in the embryo, eventually you get to polarity as it controls those aspects. Then from the literature you take what is already known and connect the dots to see what further evidence is needed. Therefore some of the research in the paper has been done before, but there are some novel aspects. For example, all of the measurements we took are new. The mouse embryo as a model organism has its strengths and weaknesses. For example, it is not a good system for identifying new proteins or new modules of signalling, and therefore for this you have to look elsewhere.
JYI: The results you gathered are from experiments on mice? How easily can this be applied to the human development?
So I would say very easily. A mouse embryo is very, very close to a human one before it is implanted. If you looked at a picture of a human and mouse blastocyst, unless you were an expert, you would not see a difference, so they are very close in terms of architecture. However, there are differences in the molecular contacts and therefore I am interested in the biophysics and the shape behind it. It is very important that the tools used in the labs are non-invasive. This controls the two most crucial factors of ensuring that we do not destroy the embryo nor modify the genome.
JYI: In order to measure contractility, you measured the surface tension of blastomeres – how did you do this?
Using very, very fancy equipment… no! Just a glass micropipette that applies pressure to the cell at the surface. The pressure is created by a siphon water reservoir at two different heights. It is very low tech.
JYI: Were the results what you were expecting?
More or less, yes. Again, a lot of the cellular biology was done by someone else in either drosophila or cell culture so it was predictable. The only surprise was the mechanosensing - I was not expecting that. When you look at how the cells differentiate into either the placenta or embryo tissue they do it according by their position. Cells at the surface form the placenta, while those inside form the embryo which is dependent on the Yap pathway. The Yap pathway allows for the expression of genes that are fundamental for the development of the placental tissue. In the mouse this is controlled by cell-cell contact and polarity but some reports from cell culture in the literature say mechanical forces also influence yap too. This is controversial. When we affected the mechanical forces by blocking the mean by which cells could go inside where the embryo would form, we would expect all of the cells to become placenta. However, they actually formed a big ball of embryo tissue, so the cells may be able to sense the mechanical forces.
JYI: How will this information be used?
So the mechanosensing I have no idea. Actually, I think there are some stem cell clinics that use drugs to prevents contractility and use it to keep the stem cells undifferentiated but I don’t think they know why it works, they just use it because it does. An explanation could come from mechanosensing. For the medical implications to human embryos that could come quickly after you consider the ethical implications. There could also be applications to use in Fertility clinics. During the experiment we noticed that the cells in the blastocyst have a rhythmic contraction which you can use to tell whether they are going to become placenta or embryo tissue. This is useful for use in the clinic as during preimplantation diagnostics they take out a cell and sequence the genome to look for diseases. Knowing which type of cell they are removing will reduce the chances that the embryo with develop abnormally. The rhythmic contraction can be seen by viewing the movement with a faster time revolution.
JYI: What further investigations are you planning?
Now in my own lab, we are looking more at the rhythmic contractions, as we know nothing about it. It’s also pretty to watch. I will continue to use the micropipette to measure surface tension to ask other questions about development in different embryos. However, more generally One of the key question we are trying to answer is how the embryo gets across scales both in time (from minutes to days) and space (from cell to tissue). There are fascinating emerging properties when you change scales.
JYI: You mentioned that biophysics is relevant to your research, what other scientific disciplines are required in your work?
So, what I do is talk a lot with physicists who don’t do experimental work but only deal with the theory. This is something that is not new; biologists and physicists have been talking to each other for a long time! There is a lot of exciting physics that can be done with biologists. One thing that I am fascinated by is that you can make an embryo on a computer which looks exactly like a real embryo in terms of shape based on a simple, simple equation, with only three parameters from thermodynamics in the 19th century from a physicist looking at the shape of a meniscus of different liquids in tubes. Now it is shaping a mammalian embryo - it is just nuts! If we can find new equations like this, it will be very exciting.
JYI: What is your typical day at work?
I don’t have a typical day. Everything is different every day. However, now that I’m working with mice, I have to plan experiments to be done a week or two ahead of time. As experiments last over several days, I can usually squeeze two experiments per week. After the embryos are recovered, I place them under the microscope and simply check on them from time to time. In the meantime, I analyse the data from the previous experiments which is what eats up most of the time.
Since I started my group, I am just writing up grant proposal and taking care of the lab organisation. Much less fun... Nevertheless, I will be teaching a bit (8h in total) from this year onwards to a small class of Master students in Paris. I think teaching is very important and therefore very difficult to do well. I am a bit anxious about how this is going to work out.
JYI: Do you have any advice for anyone considering a career in developmental biology or any book recommendations?
Sure, you have to like the job and it has to be rewarding enough for you as you won’t get much reward, in terms of not much money or free time. There are a few job opportunities and if you like it enough you will manage. In terms of book recommendations, D’Arcy Thompson, a Scottish biologist from the beginning of the 20th century wrote a book called ‘Growth and Form’ which is very interesting.