Impressions from participants of the Cajal Training Course on Neuroepigenetics

Nora Bölicke
Balázs Széky
Isabel Bustos Martinez

Please tell us briefly about your research interests.

When I decided to study regenerative biology, my main intention was to understand how a stem cell’s fate is defined. Back then, the tissue in focus was secondary to me, but when I got the chance to join the lab of Mareike Albert, I quickly decided that I want to study the cortex with all of its complexity. I am fascinated by the fact that this tissue can be considered the seat of higher cognitive function, creativity and most of what sets us humans apart from other species. While there are significant differences in the shape, size and cellular composition of the neocortex between species, the underlying principle of neocortical development is shared among mammals. The differences of neocortices of various species are hypothesised to arise from differences in neural progenitor cell (NPC) abundance during embryonic development. This, in turn, is associated with increased proliferative potential of certain NPCs during human neocortex development, which brings me back to my original question: What are the mechanisms defining a cell’s fate and behaviour? But now, in my opinion, an even more interesting layer is added: How do these processes differ between species? One of the mechanisms that allow the precise spatial and temporal regulation of neural progenitor differentiation in the neocortex are coordinated gene expression programs. Already during my Master’s thesis, I studied gene regulatory elements active during neocortical development and got drawn towards this field. Thus, during my PhD, I aspire to further contribute to our understanding of epigenetic regulatory mechanisms involved in human cortex development. I hope to achieve that aim by characterising the Polycomb group (PcG) protein complexes, a family of epigenetic repressors. To examine how these complexes control gene expression in human neural cells, I utilize epigenome profiling and editing in human brain organoids.

Why did you choose to participate in the Cajal training course on Neuroepigentics?

I am currently a PhD student in the Lab of Mareike Albert, where I study Polycomb group (PcG) proteins, a group of epigenetic modifiers that catalyze repressive post-translational histone modifications. Impaired PcG-regulation in humans has been associated with neurodevelopmental disorders affecting brain size. Moreover, studies in mouse models have implicated the PcG in controlling various stages of cortex development including the expansion and differentiation of neural progenitors. The aim of my PhD thesis is to examine the role of the Polycomb repressive complex 2, one of two major PcG complexes, in human neocortex development and neurodevelopmental disorders using cortical organoids. To approach this objective, I am applying different epigenome profiling and editing tools, some of which I have already established in the lab (e.g. neural cell-type specific CUT&Tag).
Participating in the CAJAL Neuroepigenetics training furthered my understanding of the various tools available for examination of the epigenome in the context of brain development and allowed me to analyze my already acquired data more efficiently. Furthermore, I hugely benefitted from a very specified and focused course on bioinformatically analysing epigenomic data, as this was lacking from previous courses I have participated in.

Did the participation in the course contribute to your current research? How?

I am already applying some of the methods that were discussed in the course. Meeting researchers with experience in acquiring and analayzing this type of epigenetic data, allowed me to improve my current experimental strategy and start my own data analysis. More specifically, I am now better equipped to run CUT&Tag on sorted cells and do parts of the bioinformatic analysis myself.

Would you recommend others to participate in a Cajal Training Course? Why?

I would definitely recommend anybody who has the chance to participate in a CAJAL Course, as it does not only give you hands-on experience with experimental methods and data analysis, but also provides you with a platform to discuss your own research with a variety of people from your field. The network you create by attending the course consists not only of students at a similar stage in the academic carreer, but also a lot more senior scientists, that are very open to share their knowledge and experience.

How did the support from ERA-Net NEURON contribute to your participation/success in the course?

ERA-Net NEURON did not only provide me with a full scholarship for the CAJAL training and therefore enabled my participation in the course, but also initially made me aware of the program and the chance to apply.

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Please tell us briefly about your research interests.

As a company researcher, I’m interested in the production in induced-pluripotent stem cell (iPSC) derived neural and glial cells. Neurons, astrocyte and microglia differentiated from human iPSCs are suitable model systems for studying nervous system physiology and neurodegenerative diseases. In addition, in our neural research group we utilize iPSC-derived neural and glial cells for chemical hazard assessment of industrial chemicals, drugs and air pollutants.

Why did you choose to participate in the Cajal training course on Neuroepigentics?

Transcriptomical analyses of brain cells provides highly detailed profiling of neuronal and glial populations in health and disease. Investigating chromatin structure and single-cell RNA sequencing allows the identification of cellular subsets emerging in nervous system development, aging, and neurodegeneration. Thus, learning new transcriptomical methods provides us great tools for tackling cellular heterogeneity of the brain, as well as for the identification of cellular and molecular targets in neurodegenerative diseases.

Name the 3 most significant things you gained from this course?

1. New, innovative technologies for studying complex gene-regulatory networks of the nervous system.
2. Comprehensive bioinformatical analysis of large-scale transcriptomic data
3. Sharing scientific concepts, questions, ideas with experts of neuroepigenetics research

Will the participation in the course contribute to your current research? How?

Astrocytes and microglia are highly heterogeneous cells of the central nervous system, which regulate synaptic, metabolic and immunological homeostasis of the brain. Deciphering glial cell subsets and their functions is of key importance in understanding how astrocytes and microglia contribute to nervous system physiology, or pathophysiology of Alzheimer’s disease, Parkinsons disease and other neurodegenerative disorders. Workshops and lectures of the Cajal course on Neuroepigenetics gave me a great insight into the current methods for analysing the epigenome of our iPSC-derived glial cells from control and diseased patients.

Would you recommend others to participate in a Cajal Training Course? Why?

Due to it’s highly intriguing, thought-provoking lectures, interactive wet-lab courses and joyful social events I’d highly recommend participation of the Cajal Training Course to every postdoc or PhD researcher in neurobiology and cell biology.

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Please tell us briefly about your research interests.

I am currently performing my PhD in Dr. Ángel Barco’s laboratory whose main focus is to understand the transcriptional and epigenetics mechanisms underlying the process of neuronal plasticity. In the last decades, epigenetics has been in the center of the spotlight as a major factor involved in the regulation of gene expression. Epigenetics are involved in the regulation of essential cognitive processes such as memory formation. In this sense, within the project I am working on, I try to get a deeper insight of the role of histone acetylation imbalances in memory encoding processes.

Why did you choose to participate in the Cajal training course on Neuroepigentics?

The Cajal training course on Neuroepigenetics undoubtedly constituted an outstanding opportunity for a first-year PhD student such as myself. Not only could I master some of the leading-edge techniques that are currently being used in this field but we also had the opportunity to attend seminars of some of the most renowned scientists in the field. What is more, sharing this experience with other researchers generated very interesting scientific discussions which are very beneficial for the development of our critical thinking. Overall, it constituted a very nurturing environment.

Name the 3 most significant things you gained from this course?

This experience has been very fulfilling both personally and professionally. Regarding the most significant things I gained from the course I would say:

1. Gaining confidence when engaging in scientific discussions not only with other PhD students but with renowned professors in the field. Personally, I consider that this experience contributed to developing my critical thinking, being now able to determine whether some results are reliable or which experiments would fit best to obtain a certain result.
2. Mastering some of the leading-edge techniques that are being used nowadays in the field of Neuroepigenetics. In this sense, the course offers hands-on experience training in small groups with highly skilled researchers as instructors. As a result, I acquired a deep insight on the project I embarked on.
3. Getting to know other researchers in the Neuroepigenetics field. It was a very nice experience to do networking.

Will the participation in the course contribute to your current research? How?

Undoubtedly, it has been very beneficial for the development of my project. Not only did I master different techniques that I could directly apply into my research but I also learnt different bioinformatic tools to analyze the omic data I generate in a reliable way. What is more, we established contacts with other groups which could lead to future collaborations that will undoubtedly enrich our research.

Would you recommend others to participate in a Cajal Training Course? Why?

I would strongly recommend engaging in such outstanding experience. It has undoubtedly exceeded my expectations both personally and scientifically. Without any doubt this experience has had a beneficial impact in my formation as a PhD student as I stated above.

How did the support from ERA-Net NEURON contribute to your participation/success in the course?

The support from the ERA-Net NEURON has been decisive for my participation in the course. Otherwise, I could not have attended this complete three-week course. Due to the long duration of the course and the cutting-edge techniques that were used the tuition fees were high and hence the contribution of the ERA-Net NEURON has been essential in this sense.