|PI of the laboratory: Beat M. Riederer |
Tél: 021 692 51 54 or 021 643 63 35
Email: Beat.Riederer@unil.ch or Beat.Riederer@chuv.ch
Direct supervisor (assistant): Irène Riederer
Tél: 021 643 69 45
Address: Centre des neurosciences psychiatriques (CNP), Department de Psychiatrie, CHUV, Site de CERY, 1008 Prilly-Lausanne
Role of ubiquitination of proteins in neurodegeneration
Description of Project:
Introduction: Main focus is protein oxidation and ubiquitination of brain proteins as part of mechanisms that modulate protein function or that inactivate proteins and target misfolded proteins to degradation. This is especially the case during brain aging and on mechanism involved in neuro-degeneration such as events occurring in Alzheimer’s disease (AD). Previously we have identified a variety of proteins involved in degenerative events and to be more pronounced in disease. However, many mechanisms still escape a correct identification and a variety of proteins and their sepcific role in neurodegeneration need to be explored.
Question / Aim of the work: Currently we identify a variety of proteins that may be specifically modified by ubiquitination and may be in a aberrant disease process and pathological accumulation in hallmark structures of Alzheimer's disease such as senile plaques and tangles. The aim of this work is, to quantify the extend of ubiquitination of selected proteins and relate to the degree of severity of the disease. An interesting point is the influence of environmental factors on the influence of metabolic reactions, a project that needs further elaboration.
Techniques / methods applied: This projec t will include many biochemical procedures, and is based on a proteomic approach. It includes various 1D & 2D electrophoresis, Western blots, immunoprecipitation and validation studies with normal and pathological human brain tissue and eventually may include neuroblastoma cells that are exposed to oxidative stress to modify and monitor metabolic reactions and ubiquitination.
Expected outcome: Main targets of ubiquitination are cytosekeletal structures, due to their abundance. Several enzymes of the redox system may subject to alterations. Several mutations may be subject to a change in their function and consequently included in pathological accumulations of ubiquitinated protein aggregates. According to our experience, results will be included in publications, essential for to boost the career of a young scientist.
Riederer, B.M. 2009 "Oxidation proteomics: the role of thiol modifications." Current Proteomics, 6 (1): 51-62
Riederer, I.M., M. Schiffrin, E. Kövari, C. Bouras, B.M. Riederer 2009 "Ubiquitination and cysteine nitrosylation during aging and Alzheimer's disease". Brain Research Bulletin, 80: 233-241.
Link to the group web site