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  Live imaging of injury-induced signalling and immune cell recruitment after spinal cord injury in zebrafish


   College of Medicine and Veterinary Medicine

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  Dr Leah Herrgen  No more applications being accepted  Competition Funded PhD Project (European/UK Students Only)

About the Project

Motor neurons are essential for controlling all voluntary movements. Therefore, motor neurone disease or spinal cord injury, which affect motor neuron health and viability, are debilitating neurological conditions with no effective treatment. In contrast to humans, mechanical injury of the spinal cord is followed by motor neuron regeneration in adult and larval zebrafish. The Herrgen lab is interested in the molecular and cellular mechanisms that underlie the zebrafish’s ability to repair its spinal cord and regenerate lost motor neurons. This may ultimately lead to new treatments for motor neuron disease and spinal cord injury.

Recent work from the Herrgen lab has shown that Ca2+ and H2O2 signalling are activated after mechanical injury to the spinal cord in larval zebrafish, and that H2O2 signalling is required to recruit neutrophils to the site of injury. The project will build on these preliminary findings to investigate the role of injury-induced signalling and the resulting recruitment of immune cells in successful spinal cord regeneration. The student will use transgenic fish lines expressing reporters of Ca2+ and H2O2 signalling as well as lines expressing immune cell markers to document signalling and immune cell recruitment. To determine the functional significance of injury-induced signalling and immune cell recruitment for spinal cord repair and motor neuron regeneration, the student will exploit the powerful genetic and pharmacological tools available in zebrafish. Research will be undertaken in collaboration with Dr Thomas Becker, whose research group has extensive experience in spinal cord injury and regeneration in zebrafish.

Prerequisites
- Biomedical Science, Neuroscience, Cell Biology, Developmental Biology
- No essential technical skills required

The Euan MacDonald Centre will fully fund one UK/EU studentship to commence in autumn 2017. Potential applicants must contact their supervisor of choice to discuss the project before applying. The interviews with successful candidates will be held in late January 2017.

Funding Notes

The studentship is funded by Euan MacDonald Centre for Motor Neurone Disease and offers the opportunities to:
• shadow an MND Nurse Specialist, meet people with MND, and attend an MND clinic and/or home visit
• undertake a short placement with a Principal Investigator of a different specialty
• attend and present at six-monthly seminar afternoons featuring a wide range of Centre research
• obtain bursaries to present data at national and international meetings
• gain experience in public engagement by participating in open days and MND Awareness events.
• access the Centre’s communications pipeline to promote the student’s research

References

1. Ohnmacht J, Yang Y, Maurer GW, Barreiro-Iglesias A, Tsarouchas TM, Wehner D, Sieger D, Becker CG and Becker T (2016). Spinal motor neurons are regenerated after mechanical lesion and genetic ablation in larval zebrafish. Development 143, 1464-74.

2. Herrgen L, Voss OP and Akerman CJ (2014). Calcium-dependent neuroepithelial contractions expel damaged cells from the developing brain. Developmental Cell 31, 599-613.

3. Sieger D, Moritz C, Ziegenhals T, Prykhozhij S and Peri F (2012). Long-range Ca2+ waves transmit brain-damage signals to microglia. Developmental Cell 22, 1138-48.

4. Cordeiro JV and Jacinto A (2013). The role of transcription-independent damage signals in the initiation of epithelial wound healing. Nature Reviews Molecular Cell Biology 14, 249-62.

Where will I study?