Supervisors: Prof F Gunn-Moore, Prof T Spires-Jones
Project Description:
We have identified a new protein and biochemical pathway to be involved in neuronal growth and development of the mammalian brain. In this project, the applicant will use a series of ground breaking new technologies, developed and pioneered by the supervisors, to explore this new pathway and its implications in the development of the brain.
Previously, it was thought that the major biochemical pathways that control nerve growth had all been identified, and indeed the Gunn-Moore (University of St Andrews) laboratory helped in attaining some of this knowledge. Additionally, previous work in the Gunn-Moore laboratory had also identified a new upstream component (Willin/FRMD6) of the recently emerging Hippo signalling pathway, which until now, had only been linked to cell and tissue formation, organ development and subsequently cancer when this pathway malfunctioned. Tantalising clues from the Gunn-Moore laboratories showed that Willin/FRMD6 and the Hippo pathway, may have indirect roles in the repairing of the peripheral nervous system (Moleirinho et al., 2013). Now in collaboration with the group of Spires-Jones (an expert in mammalian synaptic biology, University of Edinburgh), we have now shown for the first time, that Willin/FRMD6 expression can directly control neuronal growth and that this is significant as Willin/FRMD6 is present in the human synapse, but with unknown function(s).
In this project, the applicant will explore the role(s) of Willin/FRMD6 in human neuronal development. This will be achieved by culturing human neuronal stem cells and then exploring their development and differentiation by manipulating the amount of Willin/FRMD6 expression (both CRISPR and iRNA technology). These modified cells will then be subject to complementary methodologies including standardised biochemical pathway analysis i.e. transfection, protein extraction, western blotting, immunocytochemistry, but also including bioinformatic data analysis from an extensive proteomic data-base we have developed. The applicant will also use novel biophotonics techniques again which we have developed including: the ability to assess optically a complete neuronal network’s electrical activity (Ashfer Saber et al., 2018), location of Willin/FRMD6 in synapses using array tomography of mammalian brains (pioneered by Spires-Jones) and novel light sheet microscopes (Vettenberg et al., 2014) some of which we have commercialised. As such the applicant will be given a true interdisciplinary training with commercialisation expertise.
References:
Afshar Saber et al., (2018) All-optical assay to study biological neural networks. Frontiers in neuroscience 12, 451.
Vettenburg et al., (2014) Light-sheet microscopy using an Airy beam. Nature Methods 11 (5), 541.
Moleirinho et al., (2013) Willin, an upstream component of the hippo signaling pathway, orchestrates mammalian peripheral nerve fibroblasts. PloS one 8 (4), e60028.
To apply for this project, please go to this link.
