Inhalt
In 2011, Christian acquired his Bachelor’s degree in Biology from the University of Cologne. Afterwards he was admitted to the Fast Track Masters / Doctoral Program of the Graduate School for Biological Sciences at the University of Cologne. During the lab rotation period of this program, he worked in the laboratories of:
- Dr. Sara Wickström on "Analysis of Interactions Between the Integrin-Linked Kinase –PINCH-?-Parvin Complex and the Protein Quality Control Machinery Hsp70- Hsp90 – CHIP"
- Prof. Dr. Ulrich Baumann on "Heterologous expression and purification of human GSTP-1"
- Dr. Michael Lammers on "Effect of Lysine-N-(?)-Acetylation on the protein function of Ran"
Since March 2013, he has started his PhD project in the group of Prof. Ulrich Baumann.
Structure-Function Relationships in Proprotein Convertase S1P
Proprotein convertases are a family of proteases that activate other proteins. One member is the mammalian subtilisin/kexin-isozyme-1 or site-1 protease (SKI-1/S1P). It activates transcription factors regulating genes involved in unfolded protein response and cholesterol systhesis; as well as proteins involved in lysosomal maturation and certain glycoproteins of viruses important for viral maturation.
S1P is a membrane bound protease and is able to cleave proteins with the recognition sequence RX(L/V/I)X with basic and hydrophobic/aliphatic residues in positions P4 and P2. In contrast to the other 7 proprotein convertases present in mammals, it does not need a basic residue at position P1.
With regard to its importance in cholesterol homeostasis and pathological conditions, a deeper knowledge of the three-dimensional structure of S1P is mandatory. Consequently, we are aiming at a better understanding of the structure-function relationship of S1P and its substrates as well as its regulation and inhibition.We are specifically interested in the following questions:
- How does S1P recognize its substrates?
- How can we specifically inhibit this protease in the context of known disorders (cancer, viral infections)?
- Which other proteins/pathways are regulated by S1P?
In order to clarify the outstanding issues, we will apply cell biological, biochemical and biophysical methods including mass spectrometry and X-ray crystallography.