StemBANCC is an ambitious programme of work but the dividends are high and we believe will be transformational for drug discovery programmes. The 5 major disease groups of interest are peripheral neuropathies, neurodegenerative disorders, neurodysfunctional disorders, diabetes and adverse drug responders.
StemBANCC is a 5 year programme divided into 12 work packages (WP). The work packages are broadly divided into provision of biomaterials and biodata (WP2 - 6), cellular phenotypic discovery (WP7-10) and assay development and validation (WP11). WP1 concerns project management including planning to ensure long term viability and WP12 concerns communication for effective integration with other EU funded initiatives.
A key objective of StemBANCC is to furnish the EU research community (academic and industry) with a biorepositry of well-characterized iPSC from different disease groups. The pipeline to establishing this biobank begins with WP2, which is tasked with robustly identifying, recruiting, clinically phenotyping and collecting tissue samples from subjects with defined disease and adverse drug responses as well as healthy controls. Biomaterials from WP2 are then passed to WP3 for reprogramming subjects’ primary cells to pluripotency and from 500 subjects, at least 1500 quality assured iPSC lines are generated. WP3 has the important work of ensuring the best methods are adopted for reprogramming and meet a minimum defined quality control criteria to then enable downstream studies unhampered by reprogramming artefacts.
WP4 has three critical tasks – firstly to coordinate the varied differentiation being undertaken by WP7-10 and develop common standards for use by all participants; secondly to develop technology to support iPSC and progenitor expansion such that all participants will be adequately supplied with sufficient starting material; and thirdly to develop some key tools for enhancing the differentiation process as well as cellular phenotyping. In regards to the latter, the provision of isogenic control iPSC lines through genome editing will be highly valued.
WP5 provides the molecular profiling support that will be required by all the other research WPs and will profile biomaterial at genomic, transcriptomic, proteomic and metabolomic levels. This data will be used to confirm cell identity following differentiation as well as enabling hypothesis generation for disease relevant cellular phenotypes. The wealth of omics data along with the rich clinical dataset needs to be securely housed, integrated and interpreted and this considerable undertaking is led by WP6. This WP will closely and reciprocally interact with clinical and non-clinical disease experts in the consortium to ensure that data interpretation is correctly contextualised and work undertaken for cellular phenotyping is well supported.
WP7, WP8, WP9 and WP10 cover the cellular phenotyping of iPSC lines from the subjects recruited to develop robust models of peripheral nervous system disease, central nervous system disease, diabetes and toxicology. These WPs have two major components: first to develop the differentiation protocol and working closely with WP4 to ensure standardisation; second to undertake a wide array of assays including targeted molecular investigation, pharmacological responses and functional studies. Adapting findings from WP7-10 into assay platforms suitable for drug screening is the task of WP11. This WP perhaps best encapsulates the strength and advantages of academic-industry partnerships since both groups must work closely together to ensure that the resulting drug screening assays are both relevant and practical value.