Traditionally, basic science has sought to enter the translational pipeline through what can be referred to as “Bottom-Up” science, that is, studies that start with a hypothesis in the lab and aim to develop clinical relevance of the findings. In some cases, notably in conventional antibiotic development, this has worked well – but it assumes one-size fits all solutions that are only as good as our assumptions about the biology of many infectious diseases such as tuberculosis. By contrast, my research focuses on a “Top-Down” approach, leveraging the power of bacterial population genomics to identify bacterial processes important for Mtb success in people and to then employ cutting-edge experimental techniques to mechanistically dissect these processes with the goal of leveraging them using new translational tools.
In my work to date, I have applied this “Top-Down” strategy to define bacterial determinants of treatment outcomes and transmission success, as evident in first-author/corresponding author publications in prestigious journals such as Science, Nature Ecology Evolution, Cell Host Microbe, Science Advances, Genome Biology, PNAS, etc. My work combines expertise in evolutionary biology and bacterial genomics, cutting-edge bacterial genetics and high-throughput experimental phenotyping.
In my own lab, I will use these tools to (1) define the biological mechanisms that enable Mtb to survive antibiotic treatment; (2) identify bacterial determinants of TB transmission success; and (3) elucidate the evolutionary mechanisms underlying the emergence of new bacterial pathogens.