Modelling brain development using human induced pluripotent stem cells

The human brain is arguably the most complex structure among living organisms. Its development from single cells into a highly elaborate and unique organ has intrigued scientists for generations, yet remains incompletely understood. Recent scientific breakthroughs in the reprogramming of induced pluripotent stem cells (iPSCs) combined with tissue modelling and genome engineering offer unprecedented opportunities to model aspects of human brain development in the laboratory. Human iPSCs can be coaxed down several developmental trajectories including into neurons, thus allowing the investigation of human developmental brain processes in vitro. Moreover, human iPSC-derived models of brain disorders promise to identify potential therapeutic targets that could significantly improve the likelihood of successfully translating preclinical discoveries to the clinic.
This project will focus on the development of cerebellar models from human iPSCs. Only a handful of studies, including from the Becker group, have reported the generation of one particular cerebellar neuron type, i.e., Purkinje cells, from human iPSCs. Major limitations of the current protocol are the cumbersome and long protocol, the heterogeneity of cell composition and maturity of the differentiated neurons, and the necessity to grow human iPSC-derived cells together with mouse cerebellar progenitors. The goal of this iCASE studentship will be the development of robust and reproducible methods to generate specific and mature subpopulations of human cerebellar neurons. Specifically, the student will test the hypothesis that the overexpression of lineage-specific transcription factors will yield highly enriched and differentiated cerebellar neurons including Purkinje cells but also, for the first time, cerebellar granule neurons.
This collaborative project will bring together the expertise of the Becker group in cerebellar biology with the knowhow of the industrial partner, Axol Biosciences, in human stem cell culture. The Becker group are one of the few laboratories worldwide and the only one in the UK culturing cerebellar neurons from iPSCs. The student will be mainly based in Oxford, but will also benefit from an extended placement at Axol Biosciences in Cambridge. Axol Biosciences are a UK-based leading stem cell company with an in-house R&D team. The Axol Bioscience scientific team comprises scientists from a variety of different backgrounds and some with many years of laboratory experience. The core expertise in the lab is in human induced pluripotent stem cells and the directed differentiation to a variety of end-stage cell types. In addition, Axol Bioscience has molecular biology and electrophysiology expertise in their laboratories, allowing functional analysis of the iPS cells. Being part of a small and growing company will give the student an industrial perspective on stem cell biology, an opportunity to see which sectors are using Axol's products and what they are used for. There will also be the chance to learn about the other aspects of the business, such as marketing, sales and logistics.