Project Details
Projekt
Ex-vivo and in-vivo spectroscopic characterization and detection of heme and heme degradation products
Subject Area
Public Health, Healthcare Research, Social and Occupational Medicine
Term
from 2012 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 198096916
This project will develop and apply advanced spectroscopic approaches (with focus on Raman spectroscopy) to characterize heme and heme degradation products (HHDPs) to gain deeper insights into mechanisms, kinetics and interactions. Spectroscopic characterization of the decay, degradation and CO release kinetics of innovative CO-releasing molecules (CORM) will provide feedback for structure-reactivity guided synthesis carried out within the consortium. The novel CORMs will be optimized for spectroscopic interaction studies in living biological cells. Hepatic stellate cells (HSCs), which play an important role in liver injury and can be modulated by HHDPs, will serve as a model. Stellate cell activation upon interaction with HHDPs will be studied in a timeresolved manner using the prominent retinol spectroscopic signature. We will evaluate whether there is a direct link between HSC contractility and retinol content. Label-free and non-invasive spectroscopic imaging techniques like, e.g., resonance Raman imaging and CARS microscopy, will be established and further advanced to enable localization studies of HHDPs and CORMs in biological cells but also to study HSCs in complex tissue environment. In order to lower the limit of detection of HHDPs to biological relevant concentration, an optical sensor for the small signaling molecule CO will be developed. Moreover, for the detection and characterization of molecular interactions in heme-protein and heme-peptide complexes a difference Raman setup with a microfluidic droplet approach will be established.
DFG Programme
Research Units
