My most significant scientific contribution here at the Institute for Genome Sciences (IGS) relates to our ground breaking work documenting extensive lateral gene transfer between symbionts and invertebrates (Dunning Hotopp et al. 2007 Science 317: 1753-1756). This paradigm-shifting discovery was highlighted in numerous news articles for both the science community and the general public. This includes a 73rd place ranking by Discover Magazine in its listing of the top 100 discoveries of 2007.
Post Graduate Education and Training
Lateral Gene Transfer in Drosophila ananassae
Our goal is to elucidate the genomic changes resulting from LGT from Wolbachia bacteria to their animal hosts. In the fruit flyDrosophila ananassae, an entire Wolbachia genome has inserted into the host 2L chromosome. We have sequenced both the insert and the endosymbiont genome and have analyzed them using comparative genomic and molecular population genetic techniques to determine the mutational pressures acting on bacterial DNA in a eukaryotic genome.
Lateral Gene Transfer in Filarial Nematodes
Approximately 120 million people worldwide have lymphatic filariasis and another 1.2 billion people, predominantly in the developing world, are at risk of infection in 83 countries and territories in Asia, Africa, the Pacific, and the Americas. Although rarely fatal, the disease causes significant pain, profound disfigurement, and substantial stigma. Our goal is to identify and target bacterial genes transferred to filarial nematodes chromosomes that may provide novel drug targets in the treatment of lymphatic filariasis and the related river blindness.
Lateral Gene Transfer in the Human Somatic Genome
Approximately 90% of the cells in the human body are commensal and pathogenic bacteria. Thus, our mucosal cells are bathed in bacterial DNA. The American Cancer Society estimates that 10% of cancers in developed countries are linked to infections, although many of the mechanisms are unknown. We hypothesize that bacterial DNA incorporates into the chromosomes of our somatic cells. Such integrations can lead to gene disruptions in somatic cells analogous to disease causing mutations resulting from insertion of retroviruses, transposons, or mitochondrial DNA.
Genomics of Neisseria meningitidis
Neisseria meningitidis is a leading cause of bacterial meningitis and septicemia globally and can lead to death or serious, permanent and disabling sequelae. Meningococcal disease incidence is cyclical, with peaks and troughs of incidence.The primary objective of this study is to identify genetic factors associated with the emergence of endemic and epidemic meningococcal disease worldwide. Long term, this research project is designed to improve our understanding of meningococcal disease dynamics and provide a basis for development of a cost-effective universal vaccine that could be used globally.
Genomics of Human Ehrlichiosis Agents
Ehrlichia chaffeensis is the etiologic agent of human monocytic ehrlichiosis (HME), one of the most prevalent, life-threatening emerging tick-borne zoonoses in the United States. By correlating the genome sequences and the transcriptome profiles of E. chaffeensis strains with the diverse disease phenotypes of these strains, we will identify the virulence determinants responsible for particular disease manifestations, disease severity, and bacterial pathogenesis.
Brown Marmorated Stinkbug Transcriptome
The brown marmorated stink bug (BMSB), Halyomorpha halys (Hemiptera: Pentatomidae), invasive insect first found in the United States in Allentown, PA, in 1998. The effects on agriculture are significant as the insects devastate various crops, such as soybeans, apples, peaches and raspberries. In 2010 alone, BMSB caused $37 million in damages. Importantly, since BMSBs have been detected as far south as Florida, the number of crops at risk of infestation has grown significantly. The rapid sequence of this insect transcriptome will likely greatly increase the pace of research on this important pest.
Dung Beetle Microbiome
The mutualistic partnering of eukaryotes and prokaryotic microbes with novel metabolic capabilities is a driving force in evolution. Beneficial symbioses influence host speciation, niche expansion, and ecosystem function. The extensive biological radiation of insects onto nutritionally incomplete diets, such as plant sap, blood, cellulose, and wood, is due to the capabilities of their vertically transmitted endosymbiotic microbiomes. We are examining the vertically transmitted, gut microbiome of the bull-headed dung beetle, Onthophagus taurus using an integrative approach focusing on the taxonomic, genetic, and functional metabolic diversity.
NIH New Innovator Award, “Impact of Bacteria-Animal Lateral Gene Transfer on Human Health” 09/30/10 through 07/30/15
NIAID GSCID Subproject, “Whole Genome Sequencing of Emergent Meningococcal Clones of Public Health Significance” in collaboration with Drs. Lee Harrison and Mary Krauland at the University of Pittsburgh, 06/01/11-05/31/13
NIAID-GSCID Subproject, “Sequencing and Comparison of Genomes and Transcriptome Profiles of Human Ehrlichiosis Agents” in collaboration with Drs. Yasuko Rikihisa and Ming Lin at the Ohio State University, 10/01/12-09/30/13