Project ID NS-MH2023_18


Co Supervisor 1A FoLSM/Department of Medical & Molecular Genetics, School of Basic and Medical BiosciencesWebsite

Co Supervisor 1B Faculty of Dentistry/Centre for Craniofacial and Regenerative BiologyWebsite

Combining stem cell modelling, bioengineering and imaging to model neurodevelopmental disorders in vitro

Neurodevelopmental Disorders (NDD), including intellectual disability and autism spectrum disorder, are a common group of conditions, affecting up to 3% of the general population, with significant societal impact. Yet, the molecular and cellular mechanisms disrupting the tightly regulated orchestration of brain development and function remain unclear. The broad and dynamic complexity of human brain development has been a challenge in addressing these issues. More recent cell culture techniques have attempted to reproduce the three-dimensional complexity of brain development and have provided important insights into cytoarchitecture. However, the heterogeneity and limited reproducibility and scalability of these models has hampered the dissection of intricate molecular mechanisms underlying many NDDs and restricted the development of therapeutic strategies to address those. Bioengineering tools have enabled the development of on-chip models that biomimic targeted aspects of cell growth and morphology, thus allowing the intricate dissection of the underlying processes governing those.

In the present project, we propose the investigate an important group of proteins, the Chromatin remodeller complex BAF swi/snf, that regulates transcription at key timepoints and is involved in NDDs. Using microfabricated devices and on-chip modelling techniques developed in the Serio lab together with iPSC and stem cell lines generated within the Dias lab we will create an in vitro bioengineered model of neurodevelopmental niche, where we will be able to control the establishment, migration and differentiation of neural progenitors niches and systematically study the effects of BAF swi/snf complex mutations on these key phases of development using live imaging techniques.

One representative publication from each co-supervisor:

Devito LG, Healy L, Mohammed S, Guillemot F, Dias C. Generation of an iPSC line (CRICKi001-A) from an individual with a germline SMARCA4 missense mutation and autism spectrum disorder. Stem Cell Research. 2021;53:102304. doi:

Hagemann C, Moreno C, Guetta L, Tyzack G, Chiappini C, Legati A, Patani R, Serio A, Axonal Length Determines Distinct Homeostatic Phenotypes in Human iPSC Derived Motor Neurons on a Bioengineered Platform. Adv. Healthcare Mater. 2022, 11, 2101817.