Dr Selina Wray,
Senior Research Fellow
UCL Institute of Neurology
JS: Can you start by explaining what you do?
SW: I run a lab which is interested in understanding the molecular biology of Alzheimer’s and other forms of dementia. That means we are basically trying to understand what goes wrong in the cells of the brain and why that results in different types of dementia.
JS: That’s a good starting point, what does go wrong?
SW: We know that all forms of dementia are caused by the progressive loss of cells (neurons) in the brains, they die over time and the loss of those cells are what results in symptoms like confusion, memory loss and personality changes. Our idea is that by understanding that at the very molecular level, so going inside the cells, will allow us to understand the sequence of events that eventually leads to neuronal death.
There are a number of things that we know go wrong. So in Alzheimer’s disease we know that there is the abnormal build-up of two proteins in the brain so one of those proteins is called amyloid and the other is called tau and my work focusses on this tau protein.
JS: What is tau?
SW: Everyone has tau protein in the cells of their brain and it has a function which is really important for all of our cells to work. A neurone has a very specialised shape and it has a long growth called an axon and this allows the cells in the brain to communicate with each other. The brain is basically like a giant circuit board with a lot of cells transmitting signals between each other and they do that through the axons. The long axons have a transport network that will allow proteins to move up and down that axon. Part of this network is called microtubule and they are like train tracks in the cells and the job of tau is to hold those train tracks in place so they are like the sleepers which hold a train track in place. We all have that in the cells of our brain but what we know happens in disease for some reason is that rather than being on the train track the tau proteins form abnormal clumps in the cells. This probably results in two things happening. First of all, the transport network in those cells break down so they can’t communicate with each other in the brain as efficiently. Secondly, having this build-up of abnormal tau likely has some toxicity to the cells. This then creates a two pronged problem which is going on in the brain.
JS: What causes this to happen?
SW: My research is to try and understand this exact question and we do that by using stem-cell models. A big problem for us in understanding any disease which affects the brain is that it is inaccessible during life. The way that we can address this gap is by using stem cells. Stem cells are essentially a blank slate; they are an unspecialised cell type which means they have the potential to be any cell type of the human body. What we can do is take stem cells and give them the correct signals to become neurons which means we can grow human neurons in the lab.
Up until about 10 years ago it was thought that if you go from a stem cell to a cell type it was thought that it was a one way street but new technology became available to the research community which said that you can take a specialised cell, such as a skin cell and you can actually take it back in time and convert it back to this specialised state. That has revolutionised research into neurology because what it means for us it that we can take skin cells from people who are living with dementia and we can make them into stem cells and we can then take those stem cells and make them into brain cells. What we now have in the lab is a “dementia in a dish” model, that we can use to try and understand the disease directly in patient cells.
JS: What does the ‘dementia in a dish’ enable you to do?
SW: If we take post mortem tissue as an example. It is incredibly informative to us but it’s disadvantage is that you are looking at the end stage of the disease so by the time someone comes to post-mortem they have lived with that disease for 5-10 years and although you can look at the changes that have happened in the brain, this is at a single “end-stage” timepoint and its difficult to put together a sequence of events. The idea is that our stem cells model will look at that from the opposite perspective. So we are taking cells that start off healthy and looking for what is the initiating thing that goes wrong. The reason we want to do that is we believe a successful treatment will be one which targets what is going wrong as soon as possible. If we can understand the very first triggers in the cells, then we can try and intervene. The cells that we are using in the lab we can then adapt so they can be used for drug screening.
JS: How do you feel about the goal of finding a treatment for dementia by 2025?
SW: I see how much effort and investment has gone into dementia research and how many trials are on-going and we just need one of those to be successful. I doubt that we will see a miracle drug but I think we will see something that has a positive effect which will allow us to use that as a basis to refine and further develop that strategy for treating Alzheimer’s. I am very hopeful that in the next decade we will see treatments that are suitable to go into clinic.