Can worms help in the fight against Alzheimer's and Parkinson's?
17 May 2016
Scientists from Canterbury Christ Church University have been awarded funding to use genetically modified worms to help with the fight against Alzheimer’s and Parkinson’s
The funding, from the Leverhulme Trust to the University, will allow academics to embark on a two year research project that will seek to identify why some versions of genes make worms more resistant to the damage caused by Alzheimer’s and Parkinson’s related proteins.
There are nearly a million people in the UK currently diagnosed with either Alzheimer’s or Parkinson’s. A figure that is expected to rise as there is still no cure for these degenerative brain diseases.
The worms, which will be given human genes relating to Alzheimer’s and Parkinson’s, have been chosen due to their accelerated life-span and close genetic link to human pathology. The project will be able to follow an individual worm’s entire life, through disease progression and monitor key stages and changes in less than a month.
Dr Simon Harvey from the School of Human and Life Sciences will lead the project, he explained: “Dementia is an increasing global concern. Whilst details of the causes of diseases such as Parkinson’s, Alzheimer’s and Huntington’s differ, they are linked by incorrect protein folding.
“To improve the outcome for people with dementia we need to understand the factors that determine who develops the disease, and how quickly the disease progresses. We understand some of this, but many questions still remain to be answered. Particularly important is to identify and understand the genetic differences between people that affect both incidence and disease progression.
“A mutation in a gene can cause cells within the brain to increase the production of protein. Those proteins then misfold and clump or stick together into ‘plaques’. At the same time ’tangles’ develop, which are twisted protein fibres formed inside a dying cell. In the case of Alzheimer’s it is the plaque and tangles that are the underlying pathology for the disease. For Parkinson’s, the excessive production of protein or misfolding causes damage to nerve cells specific to the production of dopamine. The decrease in dopamine signalling is the cause of that condition’s pathology.
“For the first strand of the project we will be using worms that have the human Parkinson’s gene and monitoring how protein is being expressed and produced, and how it aggregates or sticks together. The protein produced will be fluorescently labelled so we will be able to clearly detect how it is behaving.”
Adult worm expressing a human Parkinson’s disease related gene that is linked to a fluorescent marker.
Dr Harvey will be using worms with different genetic backgrounds, the equivalent of looking at the genetic history of distant family members, to gain a greater understanding of how genetic variations can affect the pathology of the disease.
He continued: “Preliminary data has shown that some of the worms with the human Parkinson’s gene, but with different genetic backgrounds, differ in how much protein is produced and in how it sticks together. We hope that this part of the project will help us to understand why these differences occur; why some worms are better able to tolerate the misfolding of proteins and why they vary in the overall impact Parkinson’s has upon the worms."
A similar process will be used when looking at the development of Alzheimer’s pathology. Worms with different genetic backgrounds will have the human Alzheimer’s gene, but in this case Dr Harvey will look at what happens to the development of the disease as the worms’ age.
“As the worm gets older they will experience greater paralysis due to more and more protein plaques and tangles. It’s actually a very close mirror to the pathology of Alzheimer’s in humans” continued Dr Harvey.
“Here we will be looking at whether there is genetic variation between worms that accelerates paralysis. The hope is that we will find a difference in one of the fundamental processes of how cells work; and because of the way the disease progresses in worms, there is a possibility that we can apply that knowledge to humans with the potential to be able to makes cells more capable of dealing with misfolded proteins that stick together.
“We hope to find a genetic marker involved in refolding proteins that will help to identify why some people are more susceptible to certain types of dementia. It might be that one genome is better at tolerating these proteins than others. It might be one is better at folding them correctly; or one might be better at breaking the protein down.”
The final part of the project will look specifically at the production and behaviour of the worms’ normal proteins as they age. By looking at three different types of proteins, it is hoped that the project will offer a general understanding of the process, one that is not specific to one disease.
Notes to editors
- The funding from the Leverhulme Trust to the University is for £88,288.
Canterbury Christ Church University
Canterbury Christ Church University is a modern university with a particular strength in higher education for the public services.
With 17,000 students across Kent and Medway, its courses span a wide range of academic and professional subject areas.
- 95% of our UK undergraduates were in employment or further studies six months after completing their studies*.
- We are one of the South East’s largest providers of education, training and skills leading to public service careers.
*2013/14 Destination of Leavers from Higher Education survey