Doctoral researcher positions in Protease Research (m/f/d)

The DFG Research Training Group (Graduiertenkolleg) 2606 ´ProthPath` offers:

Doctoral researcher positions in Protease Research (m/f/d)

The Research Training Group 2606 entitled Understanding Protease Functions in Cellular Pathways through Discovery and Analysis of Protease Substrates (ProtPath) is a German Research Foundation (DFG)-funded doctoral program for research concerning proteases, their substrates and their functions in biology and medicine. Biochemistry, cell biology, genetics, and proteomics are the key methodologies of our research endeavor.

We have formed an excellent scientific network integrating projects located on internationally renowned research institutes and departments of Freiburg University and its Medical Center. Our mission is to support the fully funded PhD work of early-stage researchers that have completed their undergraduate training in a life science subject. We aim to develop motivated, responsible, and scientifically independent researchers fit for the postdoctoral job market in academia, biotech, and industry.

Currently, positions are available for the following projects:

P1: Prof. Dr. Matthias Eder: Targeting of cancer-associated proteases: Novel theranostic radiopharmaceuticals for the treatment of pancreatic cancer

Based on the success story of PSMA-targeting radiopharmaceuticals for prostate cancer therapy, we will focus on identifying novel protease targets. In this project, we will focus on the identification and radionuclide targeting of PDAC-specific proteases located on pancreatic tumor or related stromal cells. Proteases are highly suitable for targeting by peptidic ligands since their molecular function is based on the selective recognition of peptidic sequence motifs. Moreover, many proteases possess exosites that further expand the drugable sequences. To ascertain strong expression of putative theranostic targets in PDAC, we will profile pre-existing mRNA based PDAC expression data followed by comprehensive proteome analyses to identify cell-surface proteases as well as components of the extracellular matrix as aberrant protease synthesis and activity is a hallmark of PDAC tumor biology. Once targets have been identified, inhibitors and cyclic peptides will be designed and characterized in existing organoid culture and in vivo models of pancreatic cancer to identify probes suitable for innovative imaging and targeted therapy approaches.

P2: Dr. Ruth Geiss-Friedlander: Investigating DPP9 regulation, substrate recognition, and non-catalytic functions

Proteolytic processing is a key regulatory mechanism in cell biology, with N-terminal sequences playing central roles in post-translational regulation. The intracellular protease DPP9 is unique in its ability to remove N-terminal dipeptides after proline (Xaa-Pro-↓Zaa). DPP9 has been shown to play a role in immune regulation, metabolism, and DNA repair, and its dysregulation is linked to cancer and immune disorders (reviewed in Zolg et al. 2024).

Despite its physiological importance, only a limited number of DPP9 substrates and interaction partners have been characterized. In addition to its catalytic activity, DPP9 also has non-enzymatic functions through protein interactions, highlighting the need to better understand the mechanisms regulating its activity and binding partners.

This project aims to uncover how DPP9 is regulated, identify the determinants of DPP9–substrate interactions, and define its non-catalytic functions. It offer