We are interested in host genetic diversity, bacterial variation, and how these host-pathogen genetic interactions drive tuberculosis disease states.
Systems Genetics of Tuberculosis: We leverage host diversity in mice and macrophages from wild-derived mouse strains and diverse mouse panels, including the Collaborative Cross, Diversity Outbred and BXD mammalian resources.
In parallel, we define the bacterial genetic requirements for growth and adaptation across these diverse host environments through new mycobacterial genetic approaches, including saturated libraries of transposon mutants (TnSeq), CRISPRi and knockouts generated through ORBIT (“oligonucleotide-mediated recombineering followed by Bxb1 integrase targeting”).
These combined host and bacterial genome-wide approaches allows the interrogation of each host-pathogen interaction underlying tuberculosis that can be specifically targeted by therapeutics or vaccine interventions.
Want to learn more?
Check out how we combine diverse Mammalian and Mycobacterial genetics to map the host-interacting with pathogen loci (hipQTL) across the genome. Read our latest paper on the host and pathogen genome-wide interactions underlying the many disease states of tuberculosis here!
Leveraging the Collaborative Cross mouse panel we have identified new models of distinct TB disease states and protective immunity. Check out how we identified a causal host variant here.
We leverage this dual host-pathogen system to understand how vaccines alter disease outcome in diverse hosts. Read about how host genetic background underlies BCG vaccine efficacy here.