What has been the research focus of your PhD?
Although the projects that I have been working on during my PhD have been quite diverse, the common goal has been the generation of dopaminergic neurons from various different cell sources. A hallmark of Parkinson’s disease is the degeneration of dopaminergic neurons in the midbrain and their replacement is an exciting potential curative approach.
The aim of my first project was to develop a protocol to directly reprogram skin fibroblasts into dopaminergic neurons in vitro, using samples from both healthy individuals and Parkinson’s patients. This approach is particularly attractive as it is faster and more cost effective than using either iPS or ES cells. I was able to verify that the cells generated using our protocol were in fact functional neurons. This was accomplished through both electrophysiological methods, identifying the ability of the reprogrammed neurons to generate an action potential, and DNA sequencing, to verify the expression of genes related to neuronal function.
In my second project, I investigated whether our protocol could be used in vivo, converting a subtype of glial cells into dopaminergic neurons in a mouse model. We targeted NG2 glial cells, non-neural cells that provide neuronal support and protection, but also with the capacity to be reprogrammed into neurons. In this setting, our protocol led to the generation of interneurons and not dopamine neurons –. These findings highlighted that signals that control cell fate in vitro findings did not translate completely in vivo.
In my final project, I wanted to bridge the gap between reprogramming cells in vitro and in vivo by establishing an 3D organoid culture system. We developed a protocol for differentiating human dopaminergic organoids from embryonic stem cells and fetal brain, helping us further understand the development of human dopaminergic neurons.
How did you end up doing a PhD at Lund Stem Cell Center?
I studied for a Bachelor’s degree in Biology and a Master’s degree in Neuroscience at the University of Trieste. It was during my Master’s studies that I became interested in Parkinson’s disease and began to actively search for a research group in which I could study this disease in a translational environment. I came across the Developmental and Regenerative Neurobiology research group here in Lund and it was a perfect fit.
What have been the most rewarding aspects of your PhD?
Throughout my PhD I have had the opportunity to work on a number of different projects and collaborate with researchers with expertise in areas other than my own. This has been a fantastic growing experience. Also, participating in the Professional Development Program at the Research School in Stem Cell Biology was a very valuable experience. This program included workshops, meetings and seminars that aided my development, helped me to become be more organized and how to communicate science effectively.
What has been the most challenging aspect of your PhD?
I am very passionate about research, so working with so many exciting projects it has been a real challenge to keep my focus and to not to get completely lost, starting too many different experiments and projects.
What are your future plans?
If everything goes well I will start a postdoctoral position at the University of Southern California, Los Angeles. Once there I will be shifting my research focus from neurodegeneration to neural development, working specifically with autism. I have already received a Choi fellowship award for my postdoctoral project.
Marcella will be defending her PhD thesis titled “Functional and Transcriptional Studies of Human Dopaminergic Neurons” on Friday 2nd October at 9:00 in Segerfalksalen, BMC A10.
Zoom link: https://lu-se.zoom.us/j/9248582482
Her opponent is Dr Silvia Cappello, Max Planck Institute of Psychiatry, München, Germany.