Professor

Larry P. Simpson

David Geffen School of Medicine at UCLA
Microbiologist; Molecular biologist; Educator
Area
Biological Sciences
Specialty
Biochemistry, Biophysics, and Molecular Biology
Elected
2012

Emeritus Professor of Microbiology, Immunology, and Molecular Genetics. A founder of modern molecular parasitology, whose research has focused on the structure and function of kinetoplast mitochondrial DNA (kDNA) in trypanosomes. Solved the mechanism of RNA editing by the discovery of guide RNAs (gRNAs) in trypanosome mitochondria that determine the exact sites and number of U-nucleotides inserted or deleted. Discovered that gRNAs are primarily transcribed from the thousands of catenated mini-circles in the mitochondrial kDNA network, resolving long-standing questions about their genetic role. The discovery of gRNAs that can direct proteins to defined nucleic acid sequences predated by approximately 20 years the use of gRNAs in the Nobel Prize winning development of the CRISP/Cas9 editing system by Doudna and Carpentier. Developed a predictive model of trypanosome RNA editing and the roles of multiple enzyme activities, all of which were subsequently confirmed. Isolated the core editing complex through affinity chromatography and identified approximately twenty polypeptides, demonstrating that multiple complexes interact via RNA linkers to form the active holoenzyme. Additional research included showing that all mitochondrial tRNAs in trypanosomes are nuclear-encoded and imported. Discovered that the anticodon of the imported mitochondrial tRNATrp in Leishmania is modified by intra-mitochondrial C to U editing to allow decoding of the UGA stop codon. Developed DNA-based diagnostic methods for Chagas Disease. Created a free Online Course on Molecular Parasitology. Published 219 research papers and 24 reviews and essays.

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