Cel
"β -2 microglobulin (β-2-m) is a 99 residue protein with an immunoglobulin fold. β-2-m is usually found as a part of the major histocompatibility 1 complex. This protein aggregates to form amyloid fibrils in osteoarticular tissues, leading to pathological bone destruction and the condition known as dialysis-related amyloidosis (DRA). The accumulation of β-2-m deposits has been shown to cause arthralgias, destructive osteoarthropaties and carpal tunnel syndrome. The host laboratory has characterized β-2-m amyloid assembly and developed a molecular description of the folding and aggregation mechanisms of β-2-m under relevant conditions, but the factor or factors responsible of the initiation of the aggregation process are still unknown.
β-2-m amyloid accumulates in connective tissue, causing the pathological consequences of the disease. Collagen is one of the main components of this tissue and has been proposed to be a possible contributing factor in the initiation of aggregation. Consistent with this, studies with ex vivo amyloid material show that there is a strict association between β-2-m and collagen within joints, while biochemical experiments have revealed tight binding between β-2-m and collagen.
This project will focus on the study of the interactions between collagen and β-2-m and its consequences for the formation of amyloid fibrils from a molecular viewpoint. We will study the specificity of interaction of β-2-m with different collagen sequence patterns and the influence of collagen on β-2-m stability, dynamics, and aggregation rate. For this project a complementary set of biophysical techniques, including mass spectroscometry, NMR, fluorescence, infrared spectroscopy and electron microscopy, will be used. The results will facilitate the design of small molecules or nanoparticles (copolimer, dendirmers) directed to interfere with the interaction of β-2-m with collegen as a route toward prevention of β-2-m fibrillization."
Dziedzina nauki
Temat(-y)
Zaproszenie do składania wniosków
FP7-PEOPLE-2011-IEF
Zobacz inne projekty w ramach tego zaproszenia
System finansowania
MC-IEF - Intra-European Fellowships (IEF)Koordynator
LS2 9JT Leeds
Zjednoczone Królestwo