Structure and Function of mammalian proteins and their molecular pathologies
About
Our research interest is the molecular pathology of proteins relevant in human health. This includes disease mechanisms based on molecular dysfunction as well as the misuse of host proteins by pathogens in infection.
Research Topics
- Struktural Biology,
- Crystallogry
- Elektronenmicroscopy
- CD-Spectroscopy
- membran proteins
- gamma-secretase
- PAWR
- P2X4
- NSP6
- Alzheimer
- Covid
- Pseudomonas aeruginosa
The research approach is focused on structural and biochemical methods directed towards the state dependence of molecular interactions relvant in health and their functional disturbance by mutation and misfolding or hijacking by pathogens of specifically regulatory proteins.
In Alzheimer disease the inherited Alzheimer is overwhelmingly caused be mutations of Presinilin which is part of the γ- secretase membrane protease complex which consists of four subunits: presenilin (PS), nicastrin (NCT), APH-1 and PEN-2 . γ-Secretase cleaves over 90 type-I integral membrane proteins which are involved in many physiological and pathological process. Uncleaved Presenilin functions als as a receptor for papilloma virus infection. The complex is especially relevant in Alzheimer disease. It cleaves the APP protein and produces the neurotoxic Abeta-petides. The changes in tertiary and qurtenary structure that leads to the change of product -specificity is currently not understood. We are trying to establisch the connection between mutation, change in structure and changed biochemical activity.
A more parasitic approach to protein interaction is often utilized in infection processes by virus and bacteria e.g. as in Covid-19 or by Pseudomoonas aruginosa. Here pathogens abuse specifically membrane proteins on the cell surface to gain entry into the cell for harmful proteins or DNA.
In collaboration with the Kolbe group we to established at CSSB a platform for the analysis of infection factors of Pseudomonas aeruginosa. Pseudomonas aeruginosa is an adaptive environmental bacterium and an important opportunistic pathogen, which causes devastating acute as well as chronic, persistent infections. Its ecological success can be attributed to the dynamic expression of interacting regulatory networks that drive bacterial adaptation mechanisms and the expression of virulence traits.
Dr Ge Yang
Aziz Tumeh M.Sc.
Yajing Xiao M.Sc.
Nishika Sabharwal M.Sc.
Chengcheng Tao M.Sc.
Najlaa Bassalat M.Sc.
Abhilasha Kerkmann M.Sc.
Jennifer Rothe B.Sc.
Asmaa Al-Hamdan B.Sc.