James Saenz

Research Summary
My lab’s research merges my unique background in geochemistry and microbiology and my interest in synthetic biology and bioengineering to unravel and harness the role of lipids in organizing bioactivity. My lab has recently pioneered two fronts:

1. Minimal Microbial Models for Membrane Biology: We’ve established minimal bacterial systems, notably pathogenic mycoplasma and the Minimal Cell (JCVI-Syn3), as modifiable membrane platforms amenable to synthetic genomics. This approach allows us to dissect and manipulate cell membranes, offering unique insights into lipid-mediated cellular functions and interactions. We have developed approaches to tune and minimize mycoplasma and Syn3 lipidomes, demonstrating that two lipids are sufficient (but far from optimal) for life. Using these minimal bacterial organisms, we can reintroduce genomic and chemical complexity to elucidate the crucial components of a functional cell membrane, with the ultimate goal of designing bespoke synthetic cell membranes. Expanding from studies of individual lipids, we aim to understand and engineer the lipidome’s complexity and its impact on cellular behavior in the context of environments from mammalian hosts to oceans and soils.

2. Novel Membrane Sense and Response Mechanisms based on RNA-Lipid Interactions: A groundbreaking direction in our research is exploring how lipids can selectively interact with, and modulate RNAs. Beyond exploring lipid functions, this work paves the way for developing RNA-lipid interactions to create synthetic membrane sensors and riboregulatory mechanisms. The potential to design lipid-sensitive RNAs opens new avenues for synthetic biology applications, including novel forms of lipid regulation and membrane homeostasis.