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Development and validation of organoid disease models of amyotrophic lateral sclerosis (ALS)

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  • Full or part time
    Dr K Ning
    Prof Sherif El-Khamisy
    Dr A Tsakiridis
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Amyotrophic lateral sclerosis (ALS) is an incurable and lethal disease characterized by the progressive death of motor neurons in the brain and spinal cord. The mechanism of this disease has yet to be illuminated. Based on recent research, the motor neuron losses are roughly attributed to genetic, cellular, immune and environmental abnormalities or stimuli. Moreover, these causative factors have been reported to affect each other on both cellular and molecular levels. It is not surprising that the progression of ALS is complicated because of the synchronous and consecutive dysfunctions in numerous components of the patients’ central nervous system. To investigate the interactions between all types of the cells composing the motor neural system simultaneously or continually on one platform could be helpful to understand the mechanisms underlying the neurodegeneration in ALS. In recent years, the cerebral organoid generated from pluripotent stem cells in vitro have been reported as an autonomous platform for the modelling of the development of neural system diseases. We have successfully differentiated iPSCs into 2D neural stem cells and MNs and 3D cerebral organoids from iPSCs based on published protocols.

The aims of the proposed project are: a) to induce functional organoids which contains all neural subtypes and could represent different developmental stages of motor neural system from healthy control and C9ORF72 ALS patient iPSCs respectively; b) to investigate DNA damages, cell survival pathways and electrophysiology in healthy control and C9ORF72 iPSC-developed organoids.

Funding Notes

RCUK equivalent home stipend rate per annum for 3.5 years
Home tuition fees for 3.5 years*
University of Sheffield funded studentships supported with £6500 for consumables over the course of the award
*Overseas students may apply but need to fund the difference in fees between home and overseas rate.
A first class or upper second class honours degree in a biological sciences subject or a related discipline, or a merit or distinction in a suitable MSc. Experience working in a research laboratory desirable.

Applicants must start on a full-time or part-time PhD in academic year 2020-21 (after 1 October 2020).



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