On April 28th, Mathew will be running the London Marathon to raise money for Alzheimer's Research UK, and the Alzheimer's Society. These charities provide support for vital research in neurodegenerative diseases, and each donation to them will bring us closer to fully understanding these disorders and generating a cure. Please sponsor Mathew:

We have a number of collaborative PhD projects available for 2019:

Our latest work combining aptamers with DNA PAINT to generate super-resolution images of protein aggregates has featured as a cover feature for ChemBioChem. The cover was designed by Yukun Zuo (first author). 

The Edinburgh Single-Molecule Biophysics group is pleased to welcome its newest members Alex Chappard, Owen Kantelberg, and Blair Hoggan. Alex and Owen have joined as Ph.D. students, and Blair is a fifth year undergraduate chemistry student. 

Mathew has been selected as a speaker at the 11th UK Korea Neuroscience meeting to be held in Busan, South Korea on 20-21st August. 

Our work has recently been published in Cell Reports. The study makes use of single-molecule techniques to understand how extracellular molecular chaperones bind to aggregates formed from alpha-synuclein, the protein associated with Parkinson's disease. Usually, such aggregates have hydrophobic patches exposed, and it is believed that these enable them to punch holes into cell membranes, killing the cells. However, the chaperones bind to these patches, preventing them from damaging cells. As the body ages, it may be the case that these chaperones become less effective, and this could explain why neurodegenerative diseases become more prevalent with age. 

There are many different species of alpha-synuclein, and it's therefore a challenge to know which one is a good biomarker or therapeutic target. Using highly resolved methods to study these at the nanoscale, we have helped demonstrate which form of alpha-synuclein is damaging to cells. To achieve this, we brought together a team from multiple disciplines, across different universities and a number of UK DRI centres. Harnessing the breakthroughs in single-molecule methods, single cell imaging and stem cell biology, we have been able to take a multifaceted approach to resolve a significant problem in neurodegeneration.

The study, published in Nature Communications, adds to our growing understanding of the causes of Parkinson’s and other neurodegenerative diseases, and could influence drug design in the future.

We found that in neurons, clumps of alpha-synuclein moved to and damaged key proteins on the surface of mitochondria - the energy powerhouses of cells - making them less efficient at generating energy. They also triggered a channel on the surface of mitochondria to open, causing them to swell and burst, leaking out chemicals that tell the cell to die.

These findings were replicated in human brain cells, generated from skin cells of patients with a mutation in the alpha-synuclein gene, which causes early-onset Parkinson’s disease. By turning patient skin cells into stem cells, we could chemically guide them into become brain cells that could be studied in the lab. This cutting-edge technique provides a valuable insight into the earliest stages of neurodegeneration - something that brain scans and post-mortem analysis cannot capture.

In order to be able to do our research, we rely on funding from the public, either through taxes or generous charity donations. It's therefore really important to tell people what we do, and the Pint of Science series is an excellent way to do this. As part of this, Mathew presented the work of the Edinburgh Single-Molecule Biophysics Group in the Canon's Gait pub, in Edinburgh. The event was well attended, and there were some fantastic questions. It was also great to hear about the work being done by Benjamin Giblin, a Ph.D. student from the School of Physics.

After being invited to submit a review on alpha-synuclein, the protein associated with Parkinson's disease and Dementia with Lewy bodies, our paper has now been published in Seminars in Cell and Developmental Biology (http://dx.doi.org/10.1016/j.semcdb.2018.05.006).