Phd in the spotlight: Jesse Veenvliet
Jesse Veenvliet (1983) will be awarded his doctorate degree at the University of Amsterdam (UvA) on 31 October. Focusing on the characteristics of dopamine neurons, his doctoral research at the Swammerdam Institute for Life Sciences (SILS) has generated knowledge that will open up new avenues for the treatment of Parkinson's disease.
What was your research about?
‘I studied the substantia nigra, a midbrain structure that contains neurons which produce dopamine. Nerve fibres transmit this dopamine to the brain nuclei involved in generating movement. In Parkinson's disease, neurons in this brain region degenerate and die off. The resulting dopamine deficiency leads to symptoms such as trembling and stiffness. Right next to the substantia nigra is the ventral segmental area (VTA), which also has dopamine-producing neurons, but with the key difference that these neurons are not susceptible to degeneration. This difference probably traces back to intrauterine development. To discover what distinguishes these neurons, I studied that early phase of development.’
How did you do that?
‘I used micro array profiling technology to analyse the genetic make-up of both types of neurons in mouse embryos. This technique throws small RNA sequences on a chip, as it were, and then looks at the quantity of RNA. The more RNA present, the louder the volume of that gene – in other words, the greater its effect. We found around 300 genes that are activated in substantia nigra neurons but not in VTA neurons. The fact that they're activated in the substantia nigra means they could be involved in those neurons' susceptibility to degeneration, or, alternatively, protect against it. What we found was that 77 of these genes are less active in Parkinson's patients, giving us an additional signal that they play a part in this disease.’
What impact will this finding have?
‘The more we know about how neurons in the substantia nigra work, the better they can be reproduced. For example, using stem cell therapy. That's a process in which you create new cells to replace cells that have died. This technology isn't safe to use yet as it has not yet been possible to replicate neurons that are perfect copies of those in the brain. Introducing them in the brain could cause serious side effects, even tumours. Though there are medicines to treat Parkinson's disease, they mostly combat the symptoms. Plus, they have lots of side effects, such as psychosis.’
Was doctoral research what you expected?
‘Not entirely. I started out a bit overconfident. Recently, I stumbled on a to-do list I made back when starting my research, listing six things I wanted to do in the first six months. In the end, completing the first three took the whole of my PhD. However, I did do ten other things. And, fortunately, my supervisor – Marten Midst – gave me the freedom to do that. During the course of my PhD, I discovered a keen interest in the bioinformatics and statistics side of the research, and as a result the post doc I've just started in Berlin has a heavy emphasis on bioinformatics. At the moment, I'm studying the mechanisms driving tissue differentiation during early embryonic development, for which I'm using RAN-Seq technology, which is a step beyond micro array. This generates huge data sets that then require thorough analysis using bioinformatics. It's fascinating work!’