Dr Alasdair MacKenzie

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I am interested in understanding the regulatory mechanisms that control the expression of neuropeptides expressed in areas of the body such as the hypothalamus, amygdala and dorsal root ganglia that control appetite, mood and pain and to define the functional effects of polymorphisms and DNA-methylation.  Using genomic bioinformatics we have discovered promoters and enhancers that support expression of neuropeptides such as substance-P, NPY, galanin, BDNF as well as the CNR1 gene that encodes the CB1 receptor in the hypothalamus, hippocampus, DRG and amygdala. We have also been able to identify the signal transduction pathways that control the activities of many of these enhancers and promoters and to define the effects of disease associated polymorphisms and epigenetic modification on these activities in specific cells using primary cell transfection and the generation of transgenic mice. By determining the effects of disease associated genetic and epigenetic modification on the regulatory mechanisms that control the expression of these genes we hope to gain a greater understanding of the genetic and epigenetic mechanisms that contribute to conditions such as obesity,chronic pain and depression.