How two signalling pathways promote the creation of the blood-brain barrier
MTZ®-MPI-Award 2018 for Dr. Kathleen Hübner
The MTZ®foundation will be honouring Dr. Kathleen Hübner on 8 November 2018. She completed an important doctoral thesis on the creation of the blood-brain barrier as part of the research group of Professor Wiebke Herzog at the Max Planck Institute (MPI) for Molecular Biomedicine. Since 2009, the MTZ®foundation has honoured young scientists at the MPI for Molecular Biomedicine every year with the MTZ®-MPI-Award, which includes a prize in the amount of EUR 2,500. In this way, the benefactors, the married couple Monika and Thomas Zimmermann, want to help young scientists on their route into research.
To perform at its best every day, our brain needs oxygen and nutrients. In addition, sensitive nerve cells must be protected against harmful substances and infectious agents. In order to perform these special functions in the brain, the brain blood vessels responsible for material exchange develop a special protective barrier, the so-called blood-brain barrier. To this end, on the one hand, the individual blood vessel cells create especially stable cell-to-cell connections, and on the other hand they produce special nutrient transport molecules to ensure that the nerve cells are supplied with nutrients in spite of this barrier.
In nervous system diseases, the blood-brain barrier is often identified as damaged or malfunctioning, e.g. in the case of multiple sclerosis, Alzheimer’s or epilepsy. At the same time, a functional blood-brain barrier can disable treatment of diseases because many medications cannot penetrate this barrier. Therefore, it is important to understand the processes to create and maintain the blood-brain barrier. In her doctoral thesis, Kathleen Hübner analyzed zebrafish embryos to learn about the growth of vessel networks and the creation of the blood-brain barrier.
“One signalling pathway required to create brain blood vessels is called the Wnt signalling pathway. If this is absent to begin with, no endothelial cells can enter the brain and form vessels there,“ Kathleen Hübner says. However, so far it is not yet known why Wnt signals in the brain are so essential for the behaviour of endothelial cells and what processes are controlled by Wnt.
“I was able to dynamically block Wnt signals in zebrafish embryos and for the first time observed the effect on the behaviour of endothelial cells in the brain. I was able to show that Wnt signalling pathways are required for the ‘anastomosis’ of endothelial cells in the brain, i.e. the production of cell-to-cell contacts and their combination to form a new blood vessels,” Kathleen Hübner says.
In this context, Wnt in the endothelial cells suppresses a further signalling pathway imparted via sphingosine-1-phosphate (S1p), which is only needed for the blood-brain barrier later on. “In other words, the Wnt signalling pathway in the endothelial cells in the brain controls the timing when the blood-brain barrier is formed, because it suppresses the S1p signalling pathway in the endothelial cells until the blood vessel formation is completed,” Kathleen Hübner says.
Clinics and clinical studies are already using or testing medication which affects the Wnt or S1p signalling pathways. A better understanding of how these influence the development of blood vessels and the blood-brain barrier could also help to decide in future for which individual diagnoses such medication could help patients or when it should be avoided.
About the awardee
Kathleen Hübner (28) completed her Bachelor and Master’s degrees in Biomedical Science at the Philipps-University Marburg in the specified period of 6 years and during this time spent one research placement semester at the Harvard Medical School in Boston, USA. From the start, she has been especially interested in cell biology. She commenced her doctoral thesis immediately after her studies in March 2015 under Prof. Wiebke Herzog. In August 2018, she successfully completed her doctoral examination with summa cum laude.
In addition to her recently published study in Nature Communications, Kathleen Hübner is also the author of a second publication in Developmental Biology and co-author of a publication in the well-respected magazine Blood.
Her excellence became apparent early on in her career: At her Grammar School (‘Gymnasium’) in Görlitz, Kathleen Hübner was awarded a prize as the best in her year, she was chosen for the CiM-IMPRS Research Training Group, gained a scholarship for Germany awarded to talented students, and her contribution to a conference was chosen twice to be presented as a lecture.