Emma began her studies at Cardiff University where she obtained her Master’s degree in Biology. During her time at Cardiff she undertook a placement under the supervision of Professor M. Li during which she was first introduced to using hiPSCs to model neurodegenerative disease. She went on to work as a contractor for Eli Lilly, designing and conducting medium-high throughput drug screens using hiPSC-derived neurons. A combined interest in the understanding of neurodevelopment and passion for the use of in vitro models led her to pursue a PhD at Radboud University Medical centre under Dr. N. Nadif Kasri through the SCilS partnership, where she will be studying the role of cilia specific proteins in vitro within the context of early neurodevelopment.

Abstract
Joubert syndrome belongs to a subclass of diseases that affect the cilia – termed ciliopathies. Joubert  syndrome (JBTS) is caused by mutations in genes encoding for proteins involved in homeostasis of  the primary cilia, a specialized organelle that acts as a signalling hub, facilitating and transmitting  developmentally important signalling pathways. The defects that lead to ciliary malfunction in JBTS  result in heterogeneous physical manifestations with multiorgan involvement, but a unifying trait is  the development of thickened and elongated superior cerebellar peduncles – termed the “molar  tooth sign” (MTS) owing to its appearance in axial section MRIs. This hallmark of JBTS is due to  defects in the decussation of the superior peduncles. While the MTS is a hallmark of JBTS, it is not  uncommon for patients to develop progressive retinopathies and nephronophthisis, owing to the  importance of proper cilia homeostasis in these organs. 

Clear relationships exist between functional cilia and neurodevelopment, however there is very little understanding of the precise roles certain proteins play in the developing brain. This work aims to close gaps in the knowledge by employing human-specific in vitro models to study of the role of Joubert syndrome-related proteins: NPHP1, ARL13B, INPP5E, ARMC9, and CEP290. The work will take place in 2D inducible neuronal cultures, utilising the novel transcription factor-based direct conversion method to rapidly induce functionally active excitatory neurons to enable assessment of cell morphology and function. In addition, a 3D approach involving the generation of cerebral organoids will be employed to dissect the role cilia play in differentiation and self-organisation.