Benjamin studied for an Undergraduate MSci in Molecular Biology at the University of Glasgow before coming to Dr. William McEwan’s group at the UK Dementia Research Institute in Cambridge as a PhD student. In his PhD, Benjamin is focusing on identifying the molecular mechanisms that mediate the entry of tau protein to cells. The spreading and aggregation of tau is a pathogenic event that occurs in the brains those with Alzheimer’s Disease and many other neurodegenerative diseases. The mechanisms underlying the process of tau entry to cells were unknown. Benjamin developed a novel cell-based system to directly investigate tau entry to the cell in real-time with high sensitivity. This system has been used to identify a critical role for cellular cholesterol in preventing the entry of tau to the cell. Removal of cholesterol from cells results in extremely enhanced tau entry, and in contrast, increasing cholesterol content protects against tau entry and aggregation in brain models of disease. This work sheds light on the poorly understood link between cholesterol and neurodegeneration. Benjamin applied to the CSAR awards during the 1st and 3rd year of his PhD and was delighted to be selected as a finalist in both instances.
Alzheimer’s disease (AD) is the most common type of dementia. Throughout AD the protein tau misfolds into large fibrillar tangles which spread between cells in the human brain. Spread of tau occurs alongside degeneration, yet the underlying mechanisms remain elusive. We have developed a novel system to directly probe tau entry to cells where we have discovered a previously unidentified role for cholesterol. Importantly, we have shown that entry is a pre-requisite to spread and that modifying cellular cholesterol can reduce transmission in various models including brain slices. We believe our findings have profound consequences in our understanding of neurodegeneration.
I have contributed the vast majority of the study. I developed and optimised the system and I conceived all experiments and performed most. My supervisor and I wrote the manuscript (under review at Cell Reports). Brain slice and human stem cell culture was performed in collaboration with two colleagues.
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