Pathogenic aggregate release as therapeutic target

Lead Research Organisation: University College London
Department Name: Institute of Neurology

Abstract

Dementia Research Institute studentship

This project is aligned with the Accelerating Medicines Discovery and Translation priority area since it focuses on a pathophysiological mechanism at the basis of pathogenetic aggregate spreading in the CNS. The main disease mechanism areas are tauopathies and ALS/FTD

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
MR/R502248/1 01/10/2017 30/09/2021
1940100 Studentship MR/R502248/1 01/10/2017 30/09/2021
 
Description Alzheimer's Research UK UCL Network Pump-Priming
Amount £2,578 (GBP)
Organisation Alzheimer's Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2018 
 
Title Utilising split-GFP to assess uptake of tau 
Description Split-GFP is an existing tool which has been used to investigate co-localisation of two proteins. The GFP is an auto fluorescent beta barrel structure which has been truncated generating one single beta-strand, named GFP11 and the remaining beta strands, GFP1-10, both of which are non-fluorescent when apart. Only when the two fragments come together will the GFP reconstitute producing a fluorescent signal. This technique allows protein interaction and dynamics to be monitored in real-time live settings, in cell lines, neurons and has the potential to be used for in vivo research. In this work we have tagged tau with GFP11, and expressed cytosolically GFP1-10. 
Type Of Material Model of mechanisms or symptoms - in vitro 
Year Produced 2020 
Provided To Others? No  
Impact This split-GFP technique has been incorporated to study the uptake of tau. To date, there are no existing models to assess in real-time the time point when tau has been internalised and subsequently released into the cytosol. Due to the unknown nature of the mechanisms of tau uptake, it has not been established whether tau translocates across the membrane, or if it gets internalised within a membrane bound compartment and then released into the cytosol. This assay allows us to monitor the time following uptake that tau is released into the cytosol. In Alzheimer's disease, tau spread is a pathological hallmark; in addition the rate of spread correlates with the development of symptoms, therefore developing an assay that can detect tau uptake in real-time, gives grounds for an assay that can test pharmacological agents which can prevent this release into the cytosol, thus halting spread of tau with clinical implications. 
 
Description MRC science festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact The event was a science festival, aimed to shed light to younger children on different aspects of research, including a virtual reality tour of a research lab, stations for children to practice using lab tool e.g. pipettes and microscopes, and games and activities to help understand serious medical conditions such as Alzheimer's and Parkinson's disease.
Year(s) Of Engagement Activity 2019
URL https://www.ucl.ac.uk/lmcb/mrcfestival2019-overview