Master’s Project under the supervision of Dr Jan Gebauer

- Lab AG Baumann / University of Cologne - 

Immune therapies that reactivate the body’s own defense system have revolutionized cancer treatment and are highly successful in leukemia. In solid tumors, however, their efficacy is often limited by the extracellular matrix (ECM), which forms a physical and functional barrier that prevents immune cells from reaching the tumor.

One key ECM component is tenascin-C (TNC), which is highly expressed in the stroma of many solid tumors. TNC promotes an immune-suppressive tumor microenvironment by binding chemokines such as CXCL12, leading to stromal retention and inhibition of dendritic cells, macrophages, and cytotoxic T cells. As a result, endogenous anti-tumor immunity and immune therapies are strongly impaired.

To overcome this barrier, we developed the 19-amino-acid peptide MP5, derived from the MAtrix REgulating MOtif (MAREMO) of fibronectin. MP5 binds to the MAREMO Binding Site (MBS) of TNC, releases CXCL12, and restores immune cell infiltration. In immune-competent tumor models, MP5 enhances immune activation, induces tumor regression, reduces angiogenesis and fibroblast abundance, limits tumor cell plasticity, and alleviates side effects of radiotherapy.

Despite its strong therapeutic potential, the molecular mechanism of MP5 action is still unknown, particularly how MP5 disrupts CXCL12 binding to TNC. Understanding this interaction at structural level is essential for future drug development.

Project Aim

The goal of this Master’s project is to determine the structural basis of the MP5–TNC–CXCL12 interaction. Recombinant TNC fragments containing the MBS have already been engineered, expressed in high yield, and successfully crystallized. We will generate and analyze composite crystals with MP5, CXCL12, or MP5 + CXCL12 using X-ray crystallography, aiming to identify key interacting residues and MP5-induced changes that explain chemokine release.

Based on the structural insights, shortened and optimized peptides will be designed and tested using competition ELISA and macrophage chemoretention assays. The long-term objective is to develop improved matrix-targeting molecules with enhanced biophysical properties and reduced side effects.

Collaborative Framework

This project is part of a close scientific collaboration with
M. Koch (University of Cologne) and G. Orend (University of Strasbourg), integrating expertise in extracellular matrix biology, cancer immunity, and translational oncology.
All experimental work will be carried out in the laboratory of Jan Gebauer (University of Cologne), with regular scientific exchange and joint interpretation with the partner groups.

What you will learn

• Recombinant protein production and purification (TNC fragments; CXCL12 availability through collaboration)
• Protein–peptide and protein–chemokine interaction assays
• Protein crystallization and X-ray crystallography workflow (crystal handling → data collection/processing → structure interpretation)
• Structure-guided design of improved peptides
• Functional readouts: competition ELISA and macrophage chemoretention assays
• Working in a multidisciplinary, collaborative research environment

Suitable for Master students in Biology, Biochemistry, and Chemistry (with strong biochemical interest).
This is an unpaid Master’s project.