Visualizing the spatiotemporal dynamics and regulation of extracellular proteases

Advisor: Beatrice Ramm

Location: Friedrich Miescher Laboratory of the Max Planck Society

Our interdisciplinary group sits at the interface of biochemistry, biophysics, and synthetic biology and works towards a deeper understanding of spatiotemporal organization in biology across different scales. In this project, we are interested in investigating how extracellular and cell surface proteases shape multicellular tissues in health and in disease.

Extracellular proteases are important modulators of cell behavior and tissue function. These enzymes can either be localized freely in the extracellular space or be tethered to the cell membrane (cell surface proteases). They remodel the extracellular matrix and cleave cell-surface proteins, leading (for example) to the release of growth factors.

Since these proteases are located in the extracellular space between cells, visualizing the location and timing of their activity, as well as its regulation, has presented considerable challenges. To shed light on these processes, we have recently developed a fluorescent biosensor that uses the signal processing abilites of engineered cells to monitor extracellular proteolytic activity using fluorescence microscopy (Ramm et al., in preparation).  

In this project you will adapt the biosensor to sense the activity of a variety of extracellular proteases that are important in maintinaing tissue integrity and that are often dysregulated in disease. You  will establish appropriate cell culture models to study their activity dynamics and regulation. When and where are these proteases active? How is their activity coupled to intracellular signaling dynamics? What signaling pathways activate a specific protease? Are they activated by mechanical forces such as cell stretching?

We are looking for an enthusiastic PhD student to carry out this project in our group. You should have a basic background in molecular biology techniques, be curious and motivated, and enjoy working in a collaborative and interdisciplinary team. Experience with tissue cell culture, protein and cell engineering, fluorescence microscopy, quantitative image analysis, and computer programming (python, MATLAB) would be advantageous, but can be compensated for with a strong motivation to acquire these skills.

More information about the research of Beatrice Ramm and a selection of recent publications can be found on her faculty page.

To apply

• Check that you meet our requirements
• Familiarize yourself with the application process and have a look at the Frequently Asked Questions
• Register to apply and complete the application form

Application deadline: 27 January 2025