CNS injuries result in considerable mortality and morbidity, with limited prospects of recovery for acquired disability. Lost central nervous system (CNS) neurons are not replaced and severed CNS axons do not regenerate. The failure of CNS axonal regeneration is attributed to: (1), a lack of appropriate neurotrophic factor (NTF) stimulation to ‘prime’ neurons to growth readiness and promote axon regeneration; and (2), the presence of CNS myelin and extracellular matrix-associated axon growth inhibitors in the neuropil and wound. Understanding how to overcome the inhibition of CNS axon growth is central to devising a therapeutic strategy for promoting long tract regeneration and restoring function after CNS injury.
Three major inhibitory ligands exist in degenerating myelin including Nogo-A, myelin associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp), which collectively account for the majority of the inhibitory activity in myelin (Berry et al., 2008). All three myelin inhibitors bind to a common receptor, Nogo-66 receptor (NgR) and signals inhibition and growth cone collapse through three signal transducing binding partners, p75 and LINGO-1/AMIGO3 (Berry et al., 2008; Ahmed et al., 2013). More recently, epidermal growth factor receptor (EGFR) was also shown to signal growth cone inhibition although a mechanism which has not yet been elucidated [Koprivica2005]. Although blocking each of these receptors on their own has led to modest enhances in CNS axon regeneration, this does however, suggest that other molecules may be present in the CNS that can take part in signalling inhibition of axon regeneration.
In preliminary experiments, we have identified several genes that correlate with axon regeneration after spinal cord injury. We now wish to validate these genes in in vitro and in vivo models of spinal cord injury and wish to manipulate these genes by either over-expression or suppression of their expression using viral and non-viral vectors to understand the signalling mechanisms involved in promoting axon regeneration in the damaged spinal cord.
By joining this exciting project you can help to test these hypotheses in experiments involving in vitro and in vivo models of CNS trauma. Your project will take place within Birmingham’s Neuroscience and Ophthalmology Group where you will use cutting edge research facilities covering molecular, cellular and imaging techniques to explore the role of novel genes in spinal cord injury. You will also benefit from the vibrant interdisciplinary research environment provided by the wider Institute of Inflammation and Ageing groupings, which include scientists focussed on neuroprotection and neuroregeneration after CNS trauma and disease.
Applicants should have a strong background in Neuroscience, biomedical science or biochemistry and ideally a background in molecular neuroscience. They should have a commitment to research in molecular research and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in a relevant subject.
How to apply
Informal enquiries should be directed to Dr Zubair Ahmed ([email protected]
To apply, please send the following to Dr Zubair Ahmed ([email protected]
• A detailed CV, including your nationality and country of birth;
• Names and addresses of two referees;
• A covering letter highlighting your research experience/capabilities;
• Copies of your degree certificates with transcripts;
• Evidence of your proficiency in the English language, if applicable.
Ahmed Z., Douglas MR., John G., Berry M., Logan A. (2013). AMIGO3 is an NgR1/p75 co-receptor signaling axon growth inhibition in the acute phase of adult central nervous system injury. PLoS One 8: e61878.
Berry M., Ahmed Z., Lorber B., Douglas M., Logan A. Regeneration of axons in the visual system. (2008). Restor Neurol Neurosci 26: 147-174.
Koprivica V., Cho KS., Park JB., Yiu G., Atwal J., Gore B., Kim JA, Lin E., Tessier-Lavigne M., Chen DF., He Z. (2005). EGFR activation mediates inhibition of axon regeneration by myelin and chondroitin sulfate proteoglycans. Science 310: 106-110.