BACKGROUND:​

 

The disease I am investigating for my PhD is Progressive Supranuclear palsy (PSP), which is progressive neurodegenerative condition affecting the movement and cognitive function of typically older individuals. Like other neurodegenerative conditions such as Alzheimer’s disease (AD_ or Parkinson’s disease (PD), in PSP the tau protein, which in healthy cells has a helpful role in maintaining the cell’s shape in the cytoskeleton, misfolds and forms toxic aggregates.

 

The aim of my PhD is to investigate how brain cells are changing in response to disease pathology at the protein level. We hope that by elucidating how different cell types change in this manner, we can gain insight into their function and how this is changing in comparison to homeostasis. Currently it is unknown if different cell-types are exhibiting a protective role or are contributing to the disease process in PSP.  This work is important especially as PSP is a disease where tau is the only misfolding protein. Thus, understanding the cellular responses to it may yield results beneficial to understanding diseases with more than one types of toxic protein aggregate such as AD and PD.

 

METHODOLOGY:​​

 

I am currently using several methods, all based around looking at protein in human post-mortem tissue. At the moment I have performed lots of immunostaining to visualise protein location on 2D tissue slides. In the future, I am hoping to use techniques which allow me to examine the levels of many proteins in one sample at once simultaneously, such as mass-spectrometry.  

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​​​​RESULTS:​

 

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This picture shows microglia cells (green) next to tau protein pathology (red) in human brain tissue.

 

 

​​​​​​​​​FUTURE WORK: 

 

My next steps involve a lot of optimisations, both in the wet-lab and dry-lab! I am trying to establish some computational pipelines to analyse some data about protein levels in microglia which I recently acquired. I have taken a course on understanding mixed linear models, and am gradually learning to code, but it is all quite new, so sometimes feels quite challenging. Also, I am working on practicing a technique to extract neural cells from mouse brain tissue, to study different types of cells individually. My PhD still has quite a way to go, so I am expecting lots of changes and deviations from the current plan and am excited to adapt to what the research is telling us!

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FUNDED BY:

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I am part of the School of Clinical Medicine's Doctoral training programme at the University of Cambridge.

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​​​CONTACT: 

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