Dr Kira Bickenbach
With the Medaillenstipendium awarded by Prof. Dr. Stefan Rose-John following the Jung Medal for Medicine in Gold 2023, the Jung Foundation supported Kira Madleen Bickenbach at the Biochemical Institute of Kiel University. The project was supervised by Prof. Dr. Christoph Becker-Pauly (Research Unit Degradomics).
This prestigious award includes a fellowship currently valued at €30,000, which may be granted to an early-career scientist of the awardee’s choice.
Protease research at the interface of iron metabolism and the brain barrier
At the heart of the project was the metalloprotease meprin β. The enzyme acts like a highly specific “molecular scissor”: it cleaves selected proteins at defined sites and can thereby influence signalling pathways and transport processes.
One focus was the transferrin receptor I (TfRI), a key entry point for transferrin-bound iron into cells. Using mass-spectrometry-based degradomics approaches, Kira Bickenbach identified TfRI as a substrate of meprin β and mapped the cleavage site close to the plasma membrane. In cell models, the data showed: when meprin β cleaves the receptor, a soluble receptor form (sTfRI) is released, while fewer functional TfRI molecules remain at the cell surface.
From cell models to an animal model
In Mep1b knock-out mice, the team compared parameters of iron homeostasis with those in wild-type animals. The findings suggest that meprin β may influence iron regulation beyond TfRI alone.
Blood–brain barrier: barrier function under pressure
A second part of the project investigated meprin β at the blood–brain barrier. In a mouse model with elevated meprin-β activity in endothelial cells, key tight-junction proteins (including claudin-5, occludin and ZO-1) were reduced. Complementary measurements indicated declining barrier integrity and increased permeability—findings that may also be relevant in the context of neurological disease.
The results are being prepared for a manuscript; further work will explore the role of meprin β in disease-relevant models in more depth.
We are very happy to have been part of this study and to support this promising young researcher in his career.