Building better MiniBrains: Biomaterials directed generation of human brain organoids

Dr Yung-Yao Lin (primary)
Blizard Institute, Centre for Genomics and Child Health
Queen Mary University of London
Prof Alvaro Mata (secondary)
School of Engineering & Materials Science
Queen Mary University of London

Abstract

Organoid technologies provide physiologically relevant three-dimensional (3D) models for human tissues previously difficult to access. Using our recently developed hydrogel platform, we aim to fabricate tuneable 3D biomimetic matrices to recreate chemical and physical elements of the native extracellular matrix to study their individual/synergistic effect on improving tissue architecture and reproducibility of human brain organoids. To that end, the proposed project will integrate complementary expertise in stem cell biology and genome editing (Lin group), as well as biomaterials and bioengineering (Mata Group) to reproducibly generate human brain region-specific organoids and elucidate mechanisms underlying human brain development in health and disease.


References

1. M. A. Lancaster et al., Guided self-organization and cortical plate formation in human brain organoids. Nat. Biotechnol. 35, 659–666 (2017).
2. X. Qian et al., Generation of human brain region–specific organoids using a miniaturized spinning bioreactor. Nat. Protoc. 13, 565–580 (2018).
3. B. Lana et al., Targeted gene correction of FKRP by CRISPR/Cas9 restores functional glycosylation of α-dystroglycan in cortical neurons derived from human induced pluripotent stem cells. bioRxiv, doi:https://doi.org/10.1101/101352.
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5. K. E. Inostroza-Brito et al., Co-Assembly, spatiotemporal control and morphogenesis of a hybrid protein-peptide system. Nat. Chem. 7, 897–904 (2015).


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
BiotechnologyCell Biology
Techniques & Approaches
ChemistryEngineeringGeneticsMicroscopy / ElectrophysiologyMolecular Biology