Analysis of the Leucine Rich Repeat domain of Leucine Rich Repeat Kinase 2 andthe role of TLR4 mediated innate immune signalling in Parkinson's Disease (360G-Wellcome-099791_Z_12_A)

Parkinson's Disease is a chronic neurodegenerative disease characterised by destruction of dopaminergic neurones within the substantia nigra pars compacta region of the midbrain. This project aims to elucidate molecular mechanisms underlying Parkinson's pathology. One avenue of research involves expression, purification and analysis of the leucine rich repeat domain of 'Leucine Rich Repeat Kinase 2' (LRRK2), a molecule found to be strongly associated with Parkinson's disease by genome wide association studies. I aim to continuemy rotation work, purifying the leucine rich repeat domain of Leucine Rich Repeat Kinase 2with the ultimate aim of identifying ligands which interact with this domain, and performing x-ray crystallographic analysis for structural determination. A further line of research involves the identification of TLR4 agonists which may be involved in Parkinson's pathology in the absence of infection. I aim to purify such agonists for use in an NFKB assay to monitor TLR4 activation. I then aim to compare differences in the profile of endogenous TLR4 agonists between the wild type and Parkinson's brain.