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The organization and the role of lipid domains during myelin modeling; the role of lipids in synthesis of myelin, the fatty substance that is attacked in the brain of people with MS.

Dr. Ludovic D’Auria, a post-doctoral research associate at the University of Illinois at Chicago, is an expert researcher in the field of lipids. Dr. D’Auria has conducted much research on the interaction of lipids in the membrane and is interested in their role both beneficial and consequential in neuroscience.  He is currently working on his three-year project granted by funds from the National Multiple Sclerosis Society.

What is the purpose of your study and what are you researching?

I find my work with lipids very interesting for a couple of reasons. First, there are many different organization structures of lipids all around the body; myelin is one of those structures and its composition is about 70% lipid. Also, studying the structures of lipids in this manner has not really been paid much attention to in the past.

Because of the disease, there is a degradation of the myelin structure which leads to exposed axons which leads to disrupted electrical signaling in the brain. In my research, we are studying the structural organization of the lipids composed in the myelin, so that we can better understand what happens initially in the degradation process. With this information we can base treatment less on reacting to the consequences of the disease, and being more proactive to cut out initial events. 

I believe that this research is of a crucial nature because it has not been studied before and we lack important knowledge on the initiation of the disease. One of the reasons that my research has not been studied on this kind of scale before is because lack of technology in the past. Today, modern technology allows us to observe lipids and proteins in a stabilized state. What I mean by this is that in the past if you wanted to view proteins and lipids under intense microscopy, you would have to fix the cells and then you would be able to stabilize the protein with a solution, but it wouldn’t affect the lipids. It is similar to taking picture of an object that is moving, but is too fast for the camera, and the result is very blurred. Because of this, until very recently we have been relying on outdated and inaccurate information. Now with modern technology we can observe and decipher how the organism is behaving while it is still living and at a very small scale. 

How did you come up with this proposal for research?

During my training as a scientist, I was taught how to use these new cutting edge techniques to view, accurately, the behavior of the membranes. From this, I decided that I needed to know how all different types of lipids in membrane throughout the body were structured. 

Also, when I was earning my Ph.D. in Belgium, we saw that some lipids can form domains. These domains created new structures. We checked to make sure that it was real, and I thought that maybe it could be essential for the physiology of the organisms. And at that moment it occurred to me that I really wanted to go more in depth with these domains and see what we can learn from them.

What effect will this research have on MS if proven successful?

If we can determine the different structures of different lipids, we are hoping that one or more of these structures can be used in the diseased cells to help regenerate the myelin, and protect it from ever being destroyed by increasing myelination. Also, with this information, it wouldn’t just affect MS; it could have substantial benefits to other types of diseases and chronic disorders where lipids are in play.

My project is also interested in studying the interaction of essential proteins in the development of the myelin. When the membrane wraps around the axon to protect it, if we can find a domain that regulate this process, we can hopefully increase the productivity of myelination around the axon. With this, we can hopefully create a treatment or protocol to treat or help the membrane stay intact, or if it is destroyed, to help the myelin regenerate.

Through my research, we have seen that there are many different types of lipids that play active roles in the body. People have said that we don’t quite understand what their functions are, or if they have different roles; if they didn’t have a specific role they wouldn’t exist. Nature and the process of evolution would only have created one type of lipid if this were true.

Where are you in your research process?

Currently in this research we are growing fat cells and lipid structures to observe the molecular events that happen during the actual genesis of the cell and compare it to diseased cells to find out what is missing between the two. We take the undifferentiated oligodendrocyte and let it grow in a culture and observe what processes take over.  When we induce differentiation of the membrane, we can start to see if any domains of lipids are localizing in a specific area of the organism.

As I said before, we are studying what happens when the myelin is destroyed. We have found that a certain type of lipid – cholesterol – which is very important to the myelin starts to be misplaced in the organism, and if we can find a way to replace it, it would help prevent the myelin from being destroyed.

When we start to see that the oligodendrocyte has created the myelin that will wrap around the axon we have created a marker in the lipid to locate exactly where the process happens. With this, we are hoping to create a protocol within this process to make sure that lipid attaches efficiently and accurately.

What other projects are you currently working on/or is this the sole project?

In my lab with the help of my supervisor, we are analyzing the “Krabbe Disease” which is a disease where you have an accumulation of a certain toxic lipid, the psychosine, coming from the degradation of the galactosylceramide which is a lipid important for the myelin. This psychosine related disease induces one of the most severe neurological degenerative diseases.

We are studying how this lipid behaves in the myelin when it replaces the good galactosylceramide. We don’t know how, and that is what we are trying to find out in order to stop the disease from progressing. This will also help to understand how demyelinationin multiple sclerosis occurs.

What are your thoughts on current MS research?

In this particular area, I think that nothing big is really happening at this time. It is a very open area of research so I am hoping that with my work it will help others to zone in on the importance of lipid relations and hopefully lead us closer to a cure.

People are not (per say) afraid of working with lipids, just that because of past research and failure with studying them, they would rather do work on other aspects of the disease. But now with this new technology, I am hoping that it will become a more popular area of research and build bridges with other topics

When do you predict you will have results on your research either success or failure?

I could really start to understand how the lipid behaves and what happens when/if I modulate them within one year. It would allow me to gather my data and be able to show others what I have found, so I believe around a year because the cell models take a long time to “mature” to where I can modulate them and see some results. Within three years I hope to have deciphered how the lipids are important for the differentiation process. 

Has this research brought any further questions about MS to your mind?

While doing my work, I have realized that I would like to do further research on role of lipids during inflammation, an also important process in multiple sclerosis. I believe that they act as mediators, during the process, but I would like to work further on it to gain a better understanding on the inflammation.

How did you get connected with the National MS Society?

It emerges from my will to work in lipid disease in brain and discussions with my supervisor, whom is an excellent mentor and gives advices to set up my career.  He has done work for the National MS Society and I have been previously interested in the disease, so it came together nicely. As I wanted my own project and something that is based off of my research, I wrote a proposal and it was accepted.

Why is this work important to you? Why did you choose to work with a disease such as MS?

Because I like fundamental science in lipids but I want to also translate that into cure. MS is a disease that I can really focus on and get some good experience with lipid behavior. As well as the interaction between different lipid domains. It is helping me to become an expert in the subject, and this work will help. I am very proud of the work I am doing; I know that it will eventually be beneficial to other people and that is one of the things that drive my research.

 

Interview conducted by Elliot Gutman, Marketing Intern, National MS Society, Greater Illinois Chapter.

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