Jeffery F. Miller
University of California, Los Angeles
|
Primary Section: 44, Microbial Biology Secondary Section: 26, Genetics Membership Type:
Member
(elected 2015)
|
Biosketch
Dr. Jeffery F. Miller studies molecular mechanisms of bacterial pathogenesis and the evolution of functional diversity in bacteria and phage. He received his bachelors degree in Chemistry from Case Western Reserve University and his PhD in Molecular Biology from Tufts University School of Medicine under the mentorship of Dr. Michael Malamy. After postdoctoral training at Stanford with Lucy Tompkins and Stanley Falkow he joined the faculty at UCLA, where he now holds the Fred Kavli Chair in Nanosystems Sciences and serves as Director of the California NanoSystems Institute and Professor of Microbiology, Immunology and Molecular Genetics. Dr. Miller is a member of the National Science Advisory Board for Biosecurity and he is past chair of the General Meeting of the American Society for Microbiology (ASM). From 2012-2014 he was president of ASM. Dr. Miller is a former Pew Scholar in the Biomedical Sciences, a member of the American Academy of Microbiology, a fellow of the American Association for the Advancement of Science, and a member of the National Academy of Sciences.
Research Interests
My interests focus on evolution and adaptation in the context of microbe-host interactions. Using Bordetella species that colonize respiratory epithelia in humans and other mammals, we are probing the dynamics of global regulatory circuits that control virulence to understand how hierarchical organization facilitates adaptation and host specificity. As the obligate human pathogen Bordetella pertussis evolved from a B. bronchiseptica-like ancestor, alterations at key nodes in virulence control networks appear to be seminal events in the transition from generalist to human-restricted pathogen. Understanding these adaptations has relevance to pathogenesis and the development of improved vaccines. In a conceptually related project, Burkholderia species that replicate in eukaryotic cells are providing insight into the evolution of virulence from selective pressures in the rhizosphere. Comparative studies of environmental species with those that occasionally or obligatorily infect mammals reveals a remarkable conservation of virulence mechanisms. We postulate that evasion of predation by environmental phagocytic cells such as amoebae provides the selective pressure for virulence in humans. A vivid example is the ability to fuse membranes by injection of fuseogenic proteins across the surface of infected cells to promote intercellular spread. Finally, we are captivated by diversity-generating retroelements (DGRs), which were discovered in our laboratory. DGRs function to introduce vast amounts of targeted diversity into protein coding sequences by combining site-specific retrotransposition with nucleotide-specific mutagenesis to accelerate the evolution of adaptive traits. DGRs naturally generate libraries of protein variants that are astronomically larger than those attainable by the mammalian immune system or through available biotechnologies. Their adaptive value is illustrated by their broad distribution in Bacterial and Archaeal genomes. Current projects focus on DGRs in pathogens and their horizontal transfer between members of the gastrointestinal microbiome.
