The postholder will join the Cader Lab at the Kavli Institute for Nanoscience Discovery, University of Oxford, to lead experimental work for an ARUK Major Project grant. The project will be investigating how microglia respond to challenges in brain organoid models.

 

This will involve developing and applying advanced human iPSC-derived microglia–enriched cortical organoid models to investigate how neuronal apoptosis drives temporally and spatially organised microglial state transitions. Working closed with Dr Sally Colwey’s lab, the postholder will establish mosaic organoid models containing apoptosis-prone and apoptosis-resistant neurons, and integrate iPSC-derived microglia from defined genetic backgrounds, including APOE3/3 and APOE4/4 lines. The work will combine live imaging, single-cell RNA sequencing, 10X Xenium spatial transcriptomics, multiplexed immunohistochemistry, calcium imaging and high-density multi-electrode array recordings to define how microglial states evolve after neuronal death, how these trajectories are modified by Alzheimer’s disease genetic risk, and how they influence synaptic and neuronal network health.

 

This is an exceptional opportunity for a motivated postdoctoral scientist to contribute to a highly innovative Alzheimer’s Research UK-funded programme at the interface of stem-cell biology, neuroimmunology, spatial multi-omics and functional neuroscience. The postholder will benefit from the Cader Lab’s expertise in iPSC disease modelling, human microglia–neuron systems, genome engineering and multi-modal profiling, and will work within a collaborative environment focused on understanding how microglial responses to neuronal injury become protective or harmful in Alzheimer’s disease. The project will generate human-relevant mechanistic insight into the relationship between neuronal death, APOE genotype, microglial state composition and synaptic/network dysfunction, with the potential to identify new therapeutic strategies that shift microglia towards neuroprotective states.

 

Please see the below 'Job Description' for further details on the responsibilities and selection criteria, as well as further information about the university and how to apply.