Watch Prof Frédéric Meunier and Dr Shanley Longfield accept the research grant award and hear a bit about the project.
Project Summary:
One critical step in the pathological journey of a Tau molecule harbouring a frontotemporal dementia (FTD) mutation is the generation of aggregates in neurons, leading to neurodegeneration that affects memory, language, and behaviour. How mutated Tau becomes toxic and disrupts normal brain communication leading to cognitive decline and brain cell loss is currently unknown.
For the first time, we will harness state-of-the-art single molecule super-resolution microscopy to track Tau molecules in a living neuron as they start their pathological journey. One of our recent discoveries shows that non mutated Tau forms small droplets which help control communication between neurons. This function is crucial for memory formation and normal brain activity. However, when this process goes awry, it can contribute to diseases like FTD. Our hypothesis is that the formation and maintenance of these droplets is affected and lead to long-lasting toxic aggregates.
Our research aims to investigate how Tau FTD mutation affects its behaviour at the nanoscale level, focusing on its impact on the movement of synaptic vesicle containing neurotransmitters, essential for neuronal communication. Further, we will uncover how Tau becomes dysfunctional at the nanoscale level and how it contributes to the progression of FTD. By visualising these processes in unprecedented detail, it would provide crucial insights into how FTD develops and pave the way for future treatments. Our ultimate goal is to use this knowledge to develop new therapies that could slow or prevent the progression of FTD, improving the lives of those affected by this devastating condition.