BME 280B Seminar: Anne Nakamoto, Alan Zhang, Shelbi Russell
Presenter 1: Anne Nakamoto, BME PhD Candidate, Corbett-Detig Lab, UC Santa Cruz
Talk: Investigating deleterious mutation burden across populations and landscapes in the California Conservation Genomics Project
Description: Biodiversity is being lost at an accelerated rate due in part to anthropogenic forces, posing a threat to the sustainability of Earth’s ecosystems as well as to human health. A major goal of conservation genomics is to use genomic data to understand population health, which can inform management decisions for the preservation of biodiversity. The California Conservation Genomics Project (CCGP) is an extensive dataset containing species of conservation interest sampled across California, allowing a landscape genomics approach to conservation. Among the many metrics that can be used to assess population health is genetic load, which refers to the reduction in fitness imposed by deleterious mutations. In this work, we construct a bioinformatic analysis framework to identify deleterious genomic variants in CCGP species based on evolutionary constraint. This allows us to investigate patterns in genetic burden across populations and the landscape of California.
Presenter 2: Alan Zhang, BME PhD Candidate, Corbett-Detig Lab, UC Santa Cruz
Talk: Scalable Strain-Level Metagenomic Deconvolution and Assembly Using Pangenome Mutation-Annotated Networks
Description: Strain-level deconvolution of metagenomic samples is essential for pathogen surveillance, mixed infection diagnosis, and evolutionary genomics, yet remains computationally challenging as genomic databases expand. Existing methods scale poorly with database size or rely exclusively on single nucleotide polymorphism (SNP) information. SNP-based approaches rely on mutation-annotated trees and thus require well-established reference genomes, limiting their applicability to divergent species that lack alignable root references. We present panMAMA (panMAN Metagenomic Assignment and Metagenomic Assembly), a method that leverages the pangenome Mutation-Annotated Network (panMAN) data structure to enable accurate strain-level quantification across both closely related and divergent genomes. By employing k-min-mer-based pseudo-chaining with a seed-annotated tree index, panMAMA achieves substantial computational speedup compared to existing k-mer-based tools while maintaining high accuracy. We demonstrate that panMAMA accurately deconvolves both closely related SARS-CoV-2 genomes and divergent HIV and respiratory syncytial virus (RSV) genomes, outperforming existing tools including Freyja on simulated wastewater samples. Through a hybrid heuristic and maximum likelihood approach for read assignment and consensus calling, panMAMA effectively recovers variant genomes from low-heterogeneity samples of divergent species. These results establish panMAMA as a scalable and accurate platform that extends strain-level metagenomic analysis to previously intractable highly divergent species.
Presenter 3: Shelbi Russell, PhD, UC Santa Cruz, Ph.D., Organismic & Evol Bio, Harvard, PostDoc MCDB, UC Santa Cruz
Description: Many animals harbor bacterial symbionts that manipulate host reproduction to enhance bacterial survival and transmission. Obligate intracellular symbionts, such as Wolbachia pipientis, are particularly adept at host manipulation, influencing reproductive biology and even blocking viral replication. These bacterially induced traits have been harnessed in field studies to control mosquito populations and limit the spread of human pathogens like Dengue and Zika viruses. Despite these promising applications, the molecular mechanisms underlying Wolbachia’s interactions with host cells remain poorly understood. Furthermore, even less is known about the implications of these symbionts spreading to non-target hosts in the ecosystem. Previous work from my lab tackled these questions in vivo: we discovered that the wMel strain of Wolbachia can enhance host fertility and we discovered that even extremely low rates of horizontal symbiont transmission among hosts can influence bacterial genome evolution. However, in vivo systems offer limited resolution to identify the precise cellular mechanisms of fertility enhancement and the real-time genomic impacts of horizontal transmission. Here, we use an in vitro Drosophila system to 1) identify the cell type-specific impacts of Wolbachia infection on host-microbe interactions and 2) characterize how strains interact within host tissues during mixed infections. This simplified, easy to sample system enabled us to concentrate the effects of host cell type on Wolbachia gene expression and to control de novo strain infections and mixtures. Through these experiments, we discovered that different host cell types induce differential Wolbachia gene expression that feeds back to alter host gene expression and epigenetic silencing. These findings have motivated on-going single cell RNAseq work to resolve the process at the single cell level, during de novo infections. Results from the experimental mixed infections revealed highly reproducible strain and cell type-specific dynamics. We will leverage these discoveries to understand strain-specific tissue tropisms and how multiple strains can co-exist as superinfections in nature, which will inform future biocontrol strategies.
Bio: Shelbi is an Assistant Professor in the Department of Biomolecular Engineering at UCSC. She started her lab in 2022, after completing her PhD at Harvard University in 2016 and performing her postdoctoral work at UCSC. Her passion for studying symbiotic systems began as an undergraduate researcher at the University of Kansas describing new tapeworm species. She transitioned to studying the evolutionary genomics of bacterial-animal mutualisms in her PhD and was awarded the UC Chancellor’s Postdoctoral Fellowship and the NIH Career Development Award (K99) to test genomic hypotheses in the Wolbachia-Drosophila model system during her postdoc. As faculty, she is working to learn how hosts and microbes function and evolve so we can engineer associations for biological control. She has authored 24 papers and obtained $2.75 million in funding. Her interdisciplinary training makes her uniquely qualified to lead these investigations and has enabled novel breakthroughs in our understanding of symbiont evolution and microbe-induced host phenotypes.
Hosted by: Professor Josh Stuart, BME Department
Room: PSB-240
