Her vision: Early detection of Parkinson’s Disease
Research shows that neurodegenerative diseases are linked to proteins forming plaques in the brain. Why these plaques are formed is not yet known. Alexandra Paul, researcher at Chalmers, believes that lipid droplets are involved in the process.
Alexandra Paul is specialized in molecular microscopy. As a PhD student at the Department for Biology and Biological Engineering and the Max Planck Institute for Polymer Research in Mainz, Germany, she studied the involvement of lipids, fat molecules, in the development of obesity related diseases, using and developing advanced microscopy techniques.
“In the end of my PhD I was wondering: what can I do with my knowledge and these techniques? I realized there is quite a big gap in the understanding of the role of lipid droplets in neurodegeneration. That is the loss of structure or function of neurons, nerve cells in the brain, often resulting in the cells dying. Researchers know that lipids are important in the brain, but nobody has studied the role of intracellular lipids in detail,” says Alexandra Paul.
She wanted to change that and applied for, and received, the Swedish Research Council’s grant for an International postdoc 2019. Her project will run for three years at the University of Texas at Austin and at the division of Chemical Biology at Chalmers.
No known cure today
Neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis, ALS, can cause great suffering, both for the affected persons and their families. Hallmark of these diseases are aggregation and accumulation of proteins into so-called plaques in the brain.
When the plaques are detected, the disease is in an advanced stage, and parts of the brain have already died. Today, there is no known cure for neurodegenerative diseases. With an increasing and aging world population the number of diagnosed patients is expected to rise in the upcoming decades.
“To make a difference, treatment would have to start on people that don’t have any symptoms yet, therefore a method for early diagnoses is crucial. I want to find markers that can be detected earlier than the plaques. The hypothesis behind my project is that intracellular lipid droplet accumulation in the brain could be an indicator of a dramatic shift in the health status of the brain,” says Alexandra Paul.
Focus on lipid droplet interactions
Her project focuses on the lipid droplet interactions with α-synuclein (αS), a protein found in plaques in Parkinson’s disease. Studies have shown that lipids in cell membranes can affect the aggregation of αS. Recent studies have also discovered lipid droplets adjacent to αS-plaques in cells with Parkinson’s disease. Furthermore, lipid droplets have been indicated to occur as a stress response to oxidative stress during neurodegeneration.
“I believe that lipid droplets form in different cell types in the brain when they are stressed, and that the lipid droplets increase the speed of aggregation of the αS-protein, which leads to progression of neurodegeneration,” says Alexandra Paul.
She will use an advanced microscopy technique, called hyperspectral coherent Raman scattering (CRS), to investigate the interactions of lipid droplets and the αS-protein on a molecular level in different cells.
“Visual results appealing”
“I started to study chemistry because I am really interested in basic science processes. And I got more and more interested in techniques, optics, and looking at things. I find molecular microscopy very appealing since the results are visual,” says Alexandra Paul.
The CRS-technique is only available in approximately ten universities around the world, the University of Texas at Austin being one of them. It is based on a dye-free method displaying the characteristic intrinsic vibrational contrast of molecules. The advantage of this technique is that the lipids and proteins are not affected by an added color, which can change the physical properties of the molecules, or even be toxic.
Important to make a difference
Alexandra Paul’s goal is to provide a first overview of the link between lipid droplets and protein aggregation in the brain.
“My research will not give us a new medicine in a near future. But it might be a piece of the puzzle of understanding how neurodegenerative diseases progress. I work in fundamental research, but it has always been important to me to connect my work to health and disease. Science like this could, in the long run, lead to new medicines and treatments,” she says.
Text: Susanne Nilsson Lindh
Photo: Martina Butorac
About the Swedish Research Council’s (Vetenskapsrådets) grant for International postdoc
The purpose of the grant is to give newly qualified researchers with a doctoral degree from a Swedish higher education institution the opportunity to expand their networks and their competences by working under secure employment conditions.