Mr John Manion


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Thesis work

Thesis title: The Origins of Disease as a Guide for the Identification of New Genes and Therapies across Peripheral Nervous Disorders

Supervisors: Greg NEELY , David JAMES

Thesis abstract:

Conserved pathways across evolution from drosophila to mouse to humans can provide rich information to inform and develop new treatments for disease. This thesis uses the power of next generation sequencing and functional genomics to inform rational approaches to diseases of the peripheral nervous system including motor neuron disease, painless and painful neuropathies. Firstly, we approach motor neuron disease from human genetics and identify and validate multiple new disease genes and drug targets using drosophila as our model organism. Secondly we approach painless neuropathies from human mendelian genetics using exome sequencing, validate these genes using drosophila and interrogate the mechanism of a new mouse model of congenital insensitivity to pain. Finally we approach chronic pain from a drosophila model of neuropathic pain and establish a new treatment paradigm for chronic neuropathic pain in mice. Overall our approach demonstrates the utility of interrogating homologous systems for the identification of new pathways and treatments in peripheral nervous disorders.

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