Laura Pellegrini’s talk: Cerebral Organoids

Laura Pellegrini, a postdoc at the Lancaster lab at the MRC Laboratory of Molecular Biology in Cambridge, grows mini-brains in Petri dishes to study neurodevelopment and brain-related diseases. In her talk, she introduced us to this peculiar model system and its applications in research. 

The human brain and its complex neuropsychological disorders can hardly be modelled using animals. Still, most of what we know about the brain comes from experiments with mice. As Laura explained, cerebral organoids provide a fundamentally human yet conveniently simple model system to study brain development, bridging in vitro and in vivo techniques. Brain organoids are grown from embryonic stem cells by the addition of different factors causing cells to adopt neural identities. The result is a small spherical structure with fluid-filled ventricles.

Laura showed us intricate microscopic images of brain organoids, with each cell type marked with different colours. She highlighted that these organoids mimic the early stages of human brain development exceptionally well because they contain the same layers and cells. Of course, cerebral organoids are not exactly ‘brains in a dish’ – they don’t have functional vasculature and they lack the symmetry and complex organisation of the human brain. As Laura explained, there is plenty of room for improvement, especially surrounding reproducibility. Yet, brain organoids can already tell us a lot about neurodevelopment.  

After introducing us to the basics, Laura presented various examples of how brain organoids can be used in research. Since their recent establishment, organoids have been used in transcriptomic, electrophysiological and connectivity studies among many others. Researchers can fuse organoids of different brain regional identities to follow the migration of neurons. This method has helped determine the origin of neural populations in normal development and in disorders like autism. Remarkably, brain organoids can also inform us on evolutionary processes. In fact, Laura’s colleagues have successfully grown gorilla brain organoids. These structures appeared much smaller than their human counterparts, just like in vivo. This method has helped the group identify the potential genetic basis for the extreme expansion of the human brain compared to our closest relatives’.

Laura’s work is centred on organoids that model the choroid plexus. This understudied structure lines ventricles and secretes the cerebrospinal fluid vital for the expansion and maintenance of the brain. It also provides an important barrier between the blood and cerebrospinal fluid. In fact, many molecules, including drugs, enter the brain via this structure. Laura and her colleagues found that choroid plexus organoids secrete a fluid highly similar to cerebrospinal fluid. This led them to use organoids to study drug permeability, by adding different molecules to the media and analysing the fluid extracted from the organoids. If the drug is present in the fluid, it might also get through the barrier in vivo. Laura recently used this method to tell if the SARS-CoV-2 virus can enter the brain though the choroid plexus. Strikingly, the virus was shown to disrupt the plexus, which means it might infect the brain via this pathway.

If this wasn’t enough to impress the audience, Laura ended her talk with an even more futuristic idea. She argued that with the rise of personalised medicine, patients might have their own brain organoids grown in labs in the future, making it possible to match treatments to individuals using this model. The session ended with a light-hearted discussion about brain organoids, career choices and lab life.

If you want to watch Laura’s talk then simply join DUNE via the Durham SU page where you will get access to this and all other DUNE talks/discussions.