Jake is a PhD student in the Genomics and Computational Biology (GCB) graduate group and spent his 2nd rotation with us. He employed ‘hybrid’ (short + long read) genome assembly methods to generate one of the first complete genomes for Clostridium hiranonis, a bile-acid producing member of the gut microbiome that is implicated in maintaining gut health through the production of secondary bile acids. Jake then annotated this genome and used comparative genomic approaches to understand population genetics of C. hiranonis across animals and humans. Since there is only one other complete genome available for this organism, Jake turned to mining our shotgun metagenomic data from animal stool samples and identified ~20 samples for which the metagenomic reads provide at least 100x coverage of the C. hiranonis genome. He used contigs from the metagenome assembled genomes (MAGs) in his comparative analysis.
Shuai was a postdoc in the lab from June 2017 to October 2019, during which time he focused on using animal models to identify mechanisms that regulate dysbiosis. Using an infection model in mice, he showed that strong immune responses to infection can also promote pathogenic changes in gut microbiome composition. His first paper describing this work, showed that nitric oxide produced by macrophages during infection serves as a substrate for E. coli expansion in the small intestine, ultimately leading to barrier breakdown and subsequent sepsis. His second project in the lab used a canine model of diet-responsive inflammatory bowel disease (IBD) to dissect relationship between the microbiome and remission from IBD. His paper on this topic showed that diet therapy induced a structural change in the microbiome, marked by expansion of the bile acid producer, Clostridium hiranonis, and a comensurate decrease in levels of potential pathobionts such as E. coli and C. perfringens. He then showed that C. hiranonis was sufficient to ameliorate inflammation and E. coli expansion in a mouse model of GI disease. These findings set the stage for future work in the lab that will examine bile acid producers in modulating inflammation.
Matt (PennVet class of ‘22) spent the summer of 2019 in the lab as a NIH-BI research fellow. He continued work started by a previous student to optimize portable assays for detecting bacterial pathogens.
Megan joined the lab in October of 2017 and was a keystone of the lab until she left to start a master’s in biomedical sciences at PCOM in August of 2019. Megan handled all day-to-day operations in the lab, but her main contribution to the success of the our group involved managing all aspects of our high-throughput sequencing projects. This included everything from experiment planning; to executing technically challenging wet-lab experiments that transform raw biological samples into DNA suitable for sequencing; to operating sophisticated instrumentation used for sequencing; to troubleshooting failed experiments. During her time in the lab, she single-handedly sequenced over 1200 samples spanning over 100 projects.
Ayah was an undergraduate doing her honors thesis research in the lab until May of 2019. She was the first person in the lab to start doing E. coli competition experiments in mice infected with Toxoplasma gondii. Her data laid a rock solid foundation for work that ultimately led to this paper.
Kaylynn (PennVet class of ‘21) spent the summer of 2018 in the lab as a NIH-BI research fellow. She was the first person in our lab to profile the microbiome in a large collection of stool samples generated by the PennVet Clinical Parasitology lab from dogs with defined parasite infections. Her data showed a clear role for natural parasite infections in shaping the microbiome, and really set the stage for future work in the lab leading to this paper.
Adri (PennVet class of ‘21) spent the summer of 2018 in the lab as a supported by a fellowship from Biomeme. She expanded our portable diagnostic capabilities by testing assays for equine strangles (Strep. equi equi). Her data showed some promise for being able to detect this pathogen, and set the stage for future work by additional summer vet students.
Ying joined our lab as a volunteer in 2017 and worked her way up to being a very skilled lab manager that handled much of our early high-throughput sequencing experiments.
Francislon spent a year in the lab (April 2017-2018) working on the earliest stages of our microbiomeDB project. Even though only in the lab for a short time, his work was critical in building the core Shiny apps that are still used on our site for visualizing microbiome datasets. His work led to the first publication describing our database resource.
Ana was the first postdoc to join the lab and was instrumental in helping us gain momentum in our research endeavors and build a center that also supported research broadly across PennVet. She set up our sequencing operation, and worked closely with colleagues at PennVet and PennMed to kickstart many collaborations that would run for years. Ana was awarded a Morris Animal Foundation Fellowship, and her research focused on genome sequencing and comparative genomics of Staphyloccous species from animals and humans. Her work was the first to overturn the widely held view that Staphylococci used the mevalonate pathway for isoprenoid biosynthesis (an essential pathway for all of life), showing that this was only true for S. aureus, and that most – if not all – Staph associated with companion, agricultural and wildlife animals used a separate pathway to make isoprenoids. Her ‘One-health’ project paved the way for drug development for veterinary Staph species and highlighted a unique evolutionary aspect of Staphylococcus.