The molecular Neurobiology laboratory has generated a number of gene knockout and knockin animal models designed to investigate brain diseases. These include D1 dopamine receptor knockout; four D1 receptor expressing cell ablation mutants in which (1) the cells are killed globally throughout the brain or (2) from the cortex alone starting in early development and (3) from the cortex and basal ganglia or (4) basal ganglia alone beginning in the post-natal brain and continuing throughout adulthood; and 4 neuronal nicotinic receptor knockout and Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE) model S248F knockin lines. The behavioural, neuropharmacological, neuroanatomical and neurophysiological characterisation of these models is contributing to our fundamental understanding of a number of diseases including Huntington’s disease, nigrostriatal degeneration, dystonia and ADNFLE and drug addiction. Mechanisms of neurodegeneration including oxidative stress, apoptosis, glial mediated neuronal damage, stem cell proliferation, and cellular remodelling responses of the diseased brain to precise molecular lesioning are being studied in an effort to design effective therapeutic strategies. The nicotinic receptor knockout and knockin mutants generated by the group provide insights into models of altered nicotinic function in the brain that may ultimately explain mechanisms of dystonia, nicotine addiction and nicotine/dopamine interactions. The laboratory blends expertise in molecular and stem cell biology with clinical paradigms to design research projects that will ultimately impact on our understanding of mechanisms of neurodegenerative disease. Clinical projects have focused on developing strategies for early diagnosis of a range of neurodegenerative diseases presenting to clinicians as early impairments of cognitive functions and Parkinson’s disease.
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