In a series of interviews we’re hearing from members of the DMDD programme. Who are they? What inspires them? And what do they hope that DMDD will achieve? This month we speak to Myriam Hemberger, who leads the team’s analysis of placentas from embryonic lethal knockout mouse lines.
What has been your main area of research in your career so far?
Ever since my PhD I have been interested in studying the mechanisms that underpin placental development. Over the years we have worked on identifying chromosome “hotspots” harbouring genes that are important for placentation, studying the physiological processes that ensure the normal function of the placenta, and exploring mechanisms for gene regulation known as “epigenetic mechanisms” that make placental cells different to any other cell type found in an embryo .
What inspired you to devote your career to understanding placental development?
The placenta is absolutely essential for reproduction. The earliest cells of the placental “trophoblast” lineage allow the embryo to implant, while later on in pregnancy the placenta is the organ solely responsible for providing nutrient and gas supply to the embryo as it grows. The importance of the placenta is reflected by the fact that defects in its function can cause some of the most common and serious pregnancy complications, such as preeclampsia, fetal growth restriction, or even miscarriage. Even increased risk of childhood and adult diseases, such as cardiovascular disease or diabetes, may originate in a malfunctional placenta. The placenta has a long–lasting impact on our health and wellbeing, but it has often been under-appreciated in research.
I have always been fascinated by the types of cell that make up the placenta. Some of them have truly extraordinary capacities: they can become gigantic in size by amplifying their genome dramatically and invade into foreign tissue, completely remodelling the structure of blood vessels (an ability only shared by metastatic tumour cells). In the placenta, invasive behaviour is needed to attach the embryo to the wall of the uterus and to access maternal blood supply. These (and many other) intriguing features captured my imagination, sparking my research in this area.
What do you think is the most exciting recent development in your field?
A major milestone was Professor Janet Rossant’s work to successfully isolate and maintain stem cells from the early mouse embryo that are specific for the placenta (so-called trophoblast stem cells). The field of placental research has really been propelled forwards by the possibility to grow and manipulate these cells in culture. Recent advances mean that we now understand trophoblast stem cells and their differentiation capacity in much more detail, but there is still much to learn about what makes these cells so special and distinct from any other cell type in the embryo itself.
What is the biggest outstanding problem in your field that you wish could be solved?
Perhaps the biggest question in the field is whether such a stem cell population exists in the early human placenta and, if so, how to propagate it. This would open up the possibility to derive patient-specific stem cells and identify, in unprecedented detail, precisely which aspects of placental development are failing in specific cases of complicated pregnancy.
Why did you decide to become involved with the DMDD programme?
DMDD was proposed as a systematic screen of embryonic lethal mouse knockouts – one of the most detailed screens of its kind. But instead of screening only the embryos, a key part of the proposal was to consider the placenta as an essential (and often overlooked) organ system that must form during early development in order for an embryo to reach full gestation. It meant that we would also screen for placental phenotypes in addition to embryo phenotypes. It was a hugely exciting opportunity to make an impact on the field, as it allowed us to determine just how many genes contribute to the formation of the placenta and are therefore important to ensure normal development of the embryo.
What do you hope the DMDD programme will achieve?
Our placental analysis has already highlighted that a far greater number of genes than previously known are necessary for placental development . We find that an extraordinarily high proportion of embryonic lethal knockouts show a placental phenotype and, at least in some cases, this will mean that the placenta was either the cause or a contributing factor of embryonic lethality. One of the most important and personally rewarding achievements of the programme would be to raise awareness of this result, and to encourage others to include the placenta in studies aimed at finding the causes of developmental disorders.
What are you most proud of achieving outside of your research?
I am proud to think that some of my outreach work might have inspired young people to be fascinated by biology in the broadest sense. Ultimately, the precise field that sparks their interest is secondary – what’s important is that young people discover and develop an admiration of biological processes, for example the development of a fertilised egg to become a complete embryo and placenta. Engaging a new generation of scientists is personally rewarding, but it’s also really important to ensure the advancement of science in the future.