Type II diabetes and its associated co-morbidities are a growing global epidemic affecting an esimated 300 million patients worldwide. There currently is an abscence of therapeutic alternatives for halting or reversing disease progression. Furthermore, there is a lack of siutable human cellular models that recapitulate the biology of pancreatic beta-cells and which allow for drug screening activities at scale. AstraZeneca, in collaboration with the laboratory of Professor Douglas Melton (Harvard), are developing protocols to generate iPSC derived, functional, pancreatic beta-cells, at a scale comensurate with industry scale drug discovery. Data presented here demonstrates the succesful application of these protocols and shows the qualification of the generated cells in relation to their biological context. These cells are now being used in screening to generate novel chemical equity and identify new targets. In addition, data is presented that highlights the promise and power of combining precise genome editing (PGE) with iPSC technology to drive target validation, in a human context, with a precison and speed that has hitherto been unachievable. A specific case study is presented relating to Salt Inducible Kinase (SIK) target validation in chronic obstructive pulmonary disease. Here, PGE is applied to determine specific SIK isoform involvement in driving anti-inflamatory phenotypes in iPSC derived macrophages. This approach can be seen as a model for future combination of these two technologies in the target validation space.
Bringing Biologically Relevant Cells to Life - iPSC Technology in Discovery and Safety Assessment
Video Dec 23, 2016
Science really is everywhere! From the Big Bang to quantum mechanics to free will to ice skating, we explore it all featuring Neil deGrasse Tyson, Chuck Nice, theoretical physicist Brian Greene, neuroscientist Heather Berlin, rapper Baba Brinkman, and Olympic silver medalist figure skater Sasha Cohen.WATCH NOW
Apoptosis is an important cellular process that allows cells to die in a programmed fashion, essential for embryo development, homeostasis, and cancer development. This 3D animation provides an overview of the intrinsic and extrinsic pathways involved and demonstrates how activation of the caspase cascade occurs.WATCH NOW