Wellcome Trust PhD Student Cohort 2017
Academic and Work Experience Prior to Sept 2017 Programme Start: I completed my undergraduate degree in developmental biology (MSci) at the University of Manchester, where I worked with Professor Sue Kimber to develop iPSC models of rare skeletal disorders. During this time, I also undertook a BBSRC funded studentship to investigate wound healing in diabetes.
PhD Programme – Year 1 – MRes and Project Rotations: (1) During my first rotation project I worked with Dr Davide Danovi and Professor Fiona Watt as part of the human induced pluripotent stem cell initiative (HipSci). During this project I grew kidney organoids from patient iPSCs to model Bardet-Biedl syndrome. (2) In my second rotation project I worked with Dr Ivo Lieberam to develop in vitro neuromuscular circuits in order to model the loss of nerve-muscle connectivity in ALS. (3) In my final project I worked with Dr Franziska Denk and Professor Stephen McMahon to understand how neuro-immune interactions contribute to sex-specific differences in chronic pain.
PhD Programme – Years 2 to 4 – Doctoral Studies: Amyotrophic lateral sclerosis (ALS) is a rapidly fatal neurodegenerative disorder, characterised by progressive loss of motor neurons (MNs) in the brain and spinal cord. Surmounting evidence suggests that peripheral axonal and neuromuscular junction (NMJ) defects precede overall cell death in the disease pathogenesis. However, the molecular mechanisms underpinning these critical early events remain poorly understood. A major reason for this is the difficulty in accessing live neuromuscular junctions for study. To overcome this, we intend to engineer functional human neuromuscular junctions in vitro. Motor neurons derived from wildtype human induced pluripotent stem cells (hiPSCs) and hiPSCs harbouring an ALS-linked TDPeter HarP-43 mutation will be plated, along with astrocytes, into a microfluidics device. Axons will be able to project through micro-channels into a separate muscle compartment, where they will be able to form neuromuscular connections. Optogenetics will be used to stimulate motor neuron activity and trigger myofiber contraction, mimicking the voluntary movement that is lost in ALS. Using this platform, we will be able to apply various live imaging techniques to the study of human neuromuscular junction pathology that has not previously been possible. As such we feel this approach will provide unique insights into how TDP-43 mediates some of the earliest pathological events in ALS. Ultimately, through a collaboration with AstraZeneca, we intend to use this platform for drugs discovery.
Congratulations to Peter Harley for receiving the:
- Susan Tucker Award for the most outstanding student in the Biomedical and Translational Sciences MRes programme. October 2018.
- Centre for Stem Cells and Regenerative Medicine Award for the student scoring the highest Biomedical and Translational Science MRes degree mark and continuing to a PhD in Stem Cells and Regenerative Medicine. November 2018.
Peter Harley ORCID webpage