The Neuro Team
Heather Durham, PhD
To study why these mutant proteins accumulate and upset the physiology of the cells most vulnerable to damage, Dr. Durham has created primary culture models by expressing mutant and wild type human genes in motor neurons of mouse spinal cord cultures. Using these cultures and transgenic mouse models, her research is linking the vulnerability of motor neurons to the way in which they respond to stress and deal with damaged proteins. They are investigating why mutant proteins associated with disease are handled differently in vulnerable tissues compared to those that are resistant to damage and are looking for drugs that can boost levels of protective proteins or facilitate clearance of damaged proteins, so stressed cells can defend themselves. These studies include investigation of the fundamental mechanisms underlying the high threshold for activation of cytoprotective pathways in motor neurons.
The Durham lab has also shown that glutamatergic neurotransmission, through which motor neurons receive information from the brain and peripheral sensory neurons, promotes aggregation and toxicity of mutant proteins in a calcium-dependent fashion. They are using advanced imaging methods to monitor function and transport of organelles in living motor neurons to investigate how the stresses of normal living and the superimposition of mutant proteins contribute to the demise of motor neurons. Toxic, misfolded proteins also can be generated through damage inflicted by the cellular environment, including free radicals. Thus, it is hoped that this research will be relevant to sporadic forms of motor neuron diseases.