Tuberculosis (TB) remains the second leading cause of infectious disease mortality worldwide, killing over one million people annually. Rising antibiotic resistance has created an urgent need for host-directed therapeutics (HDTs) — preferably by …
Integrative machine learning to predict AMR and characterize pathogen genomics across clinical and environmental contexts.
Despite the fundamental importance of DNA replication for life, this process remains understudied in bacteria outside Escherichia coli and Bacillus subtilis. In particular, most bacteria do not encode the helicase-loading proteins that are essential in E. coli and B. subtilis for DNA replication. Instead, most bacteria encode a DciA homolog that likely constitutes the predominant mechanism of helicase operation in bacteria. However, it is still unknown how DciA structure and function compare across diverse phyla that encode DciA proteins. In this study, we performed computational evolutionary analyses to uncover tremendous diversity among DciA homologs. These studies provide a significant advance in our understanding of an essential component of the bacterial DNA replication machinery.
After nearly a century of vaccination and six decades of drug therapy, tuberculosis (TB) kills more people annually than any other infectious disease. Substantial challenges to disease eradication remain among vulnerable and underserved populations. …
Characterizing protein families and (patho)genomic features using molecular evolution and phylogenetics, and the MolEvolvR web application.
Discovering unique pathogenic sRNA in infected hosts
Studying stress response systems using molecular evolution and phylogenetics.
Accessory sigma factors, which reprogram RNA polymerase to transcribe specific gene sets, activate bacterial adaptive responses to noxious environments. Here we reconstruct the complete sigma factor regulatory network of the human pathogen …
Computational approaches to study host responses to infection and identify host-directed therapeutic interventions.
The bacterial envelope integrates essential stress-sensing and adaptive functions; thus, envelope-preserving functions are important for survival. In Gram-negative bacteria, envelope integrity during stress is maintained by the multi-gene Psp …