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.

She plans to submit her thesis in December 2024 and defend during 2025. Currently, Emma is seeking opportunities in the pharmaceutical sector, where she can apply the skills and expertise she developed during her PhD.

What does Emma think about our program?

My experience as an MSCA fellow has been truly fantastic! Being part of the SCilS consortium introduced me to outstanding researchers and fostered a strong collaborative environment. The program offered invaluable opportunities for both personal and professional growth, allowing us to see how research is conducted across different labs. We received training from leading experts and were encouraged to develop transferable skills, such as scientific communication, through a mix of online and in-person meetings. For me, the support network among the ESRs was a cornerstone of this experience, helping us navigate the challenges of the PhD journey together and forming lasting connections. I'm deeply grateful for the opportunities SCilS has provided—this has been a transformative experience!

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 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.

We want you to understand!

Layman abstract

Growing brains in a dish: a closer look at the role of the cell’s antenna during brain development 

My project is to understand the role that small hair-like structures on cells (known as the cilia) play in the brain before and after birth. When cilia do not function correctly this can lead to a number of diseases, including Joubert syndrome – a rare disorder that affects the development of the brain. 

We have made stem cells that have defective cilia and want to study how these cells function. To answer this question, we are making miniature brains which will help us understand how cilia affect brain development. We will also study how brain cells (neurons) communicate with each other. 

Our hope is that this work will shed light on the mechanisms behind Joubert syndrome and other diseases caused by problems with cilia function.

You can also watch a 55-sec video which Emma created to describe her research here: YOUTUBE or with others on our website here.