Marc Baggelaar graduates cum laude on body’s own marijuana

Published on April 20, 2017
Marc Baggelaar graduates cum laude on body’s own marijuana

PhD candidate Marc Baggelaar of the Leiden Institute of Chemistry (LIC) graduated cum laude on Thursday 6 April. His thesis on the endocannabinoid system in the brain is very comprehensive and of high quality, according to the jury. ‘A very talented young scientist, that definitely belongs to the top five percent'.

Fundamental and practicable

Baggelaar’s thesis is both fundamental and practicable. He designed and synthesised substances with which he could study and influence the functioning of diacylglycerol lipases. These are proteins that produce the endocannabinoid 2-AG (arachidonoylglycerol). This endocannabinoid has the same effect as THC, the active substance in marijuana: it activates the cannabinoid CB1 receptor in the brain. Influencing the functioning of this receptor is very promising in drug development, for instance for the diseases obesity and diabetes.

The role of the body’s own marijuana

The brain produces another kind of bodily marijuana, namely anandamide. What the role of both neurotransmitters is, is still unclear. Because this understanding is essential for drug development, Baggelaar looked at which endocannabinoid is responsible for the different biological processes. This includes the regulation of appetite, pain sensation, memory and anxiety. An enhanced insight in these processes could lead to alternatives for existing inhibitors of the cannabinoid CB1 receptor in the brain. Current inhibitors work well against heavy overweight and type 2 diabetes, but have the major drawback that they have suicidal side effects.

Chemical toolbox

In order to study a biological system such as the endocannabinoid system, chemical tools are of crucial importance; tools that lacked before. In the Molecular Physiology group of Mario van der Stelt, Baggelaar developed a new method to measure the activity of diacylglycerol lipases. This enables him and colleagues to explore the regulation of endogenous marijuana. With this new method, Baggelaar identified and optimised new inhibitors of  diacylglycerol lipase. The discovery of these new inhibitors is of high importance to neuroscience and the field of endocannabinoids in particular. These studies could lead to more insight in the exact functioning of the endocannabinoid system and could lead to novel drugs.

Full of praise

Promotor Hermen Overkleeft is full of praise for Baggelaar: ‘Besides his large number of publications, Marc is social and took the lead in several collaborations with experts in the Netherlands and abroad. As first PhD student in de group of Mario van der Stelt he laid the foundation for the technologies that his successors now use. What I admire, is that he changed from an excellent organic chemist into an all-round chemical biologist with an eye for detail, in only a short period of time. In addition, he has an exceptional problem solving ability: with his creative way of thinking he individually developed original molecules and concepts. 

Satisfied with the results

Baggelaar is satisfied with the results of his thesis. ‘It is important that we have contributed to research on the endocannabinoid system. That plays an important role in different diseases, such as obesity and type 2 diabetes. Therefore, a fundamental understanding of this system is an important step in the drug development on these diseases.’ At the end of this summer, Baggelaar will continue his research as a Marie Curie fellow in the lab of Professor Ed Tate at the Imperial College London.

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