Palmer Taylor

Professor, Pharmacology, UC San Diego Dean, Pharmaceutical Sciences, UC San Diego

Dr. Taylor’s research is directed to structure, recognition capacity, and regulation of expression of proteins governing neurotransmission in cholinergic synapses. His group cloned the first acetylcho-linesterase (AChE) gene 25 years ago. This was followed by analysis of its genomic DNA to delineate regulatory regions, multiple splicing options and gene expression profiles in nerve and muscle. His studies of AChE structure and its complexes by crystallography and fluorescence spectroscopy, characterizing a peripheral site on AChE and demonstrating flexibility of the active center gorge, provided the basis for studies with Barry Sharpless’ group at the Scripps Research Institute employing freeze-frame, click-chemistry. The very biological target, AChE, is used as the template in the synthesis of high affinity, selective inhibitors. Dr. Taylor’s longstanding work with nicotinic acetylcholine receptors (nAChR) defined ligand specificity in relation to state functions for receptor activation and desensitization and identified structural determinants on nAChR governing ligand and peptide toxin specificity. More recently, he examined the acetylcholine binding protein, a soluble surrogate of the receptor. His group, in collaboration, employed physical methods of fluorescence anisotropy decay, NMR, x-ray crystallography and deuterium-hydrogen exchange to examine structure and selectivity of ligand binding sites. Finally, Dr. Taylor’s group uncovered much of what is known about the structure of neuroligin, a synaptic adhesion molecule homologous to AChE and its partner neurexin. Their structural studies have delineated alterations in processing and folding associated with congenital mutations found in the autism spectrum disorders. These pathways suggest potential therapeutic modalities for this developmental condition.