Thread by @ksamocha

Jay Gopalakrishnan on brain organoids #GRD23: The human brain is one of the most complex tissue systems with many different cell types that have highly orchestrated interactions.

Brain organoids are self-assembling 3D structures that could be used to model neurological disorders

Jay Gopalakrishnan #GRD23: Brain organoids have some of the layers seen in the brain. Have been able to make organoids with two eye-like structures (are light sensitive).

Have worked out a way to make ~1000 nearly homogeneous brain organoids per batch. "Hi-Q" brain organoids.

Jay Gopalakrishnan #GRD23: Discovered a cilium checkpoint, which is key for growth.

Microcephaly neural progenitor cells have premature differentiation, which leads to depletion of these NPCs.

Jay Gopalakrishnan #GRD23: What if NPCs override the cilium checkpoint?

Cilium disassembly and cell cycle progression become uncoupled. Can see that the NPCs vs differentiated cells look 'inside-out'. Recapitulating a rare disease phenotype.

Jay Gopalakrishnan #GRD23: How often are defects in cilia dynamics implicated in rare disorders? Quite frequently (microcephaly, Fragile X, FoxG1, Rett syndrome).

Now want to do high throughput disease modelling of rare neurogenetic conditions.

Jay Gopalakrishnan #GRD23: With these brain organoid models of rare conditions, can screen FDA approved compounds + ASOs. Hoping this can help find treatments.