New Tools, New Lipids: Joshua Chamberlain Explores Bacterial Sphingolipids for Smarter Drug Delivery

At the 2025 Theobald Smith Society Spring Symposium, Joshua Chamberlain, a researcher in the Klein Lab at Rutgers University–Camden, presented a compelling exploration of lipid nanoparticles and the unique contributions bacterial sphingolipids might bring to this rapidly growing field of biomedical science.

Lipid nanoparticles (LNPs) have become a cornerstone of modern drug delivery, famously used in mRNA COVID-19 vaccines and cancer therapies. These tiny lipid-based carriers stabilize sensitive therapeutics, reduce harmful side effects, and extend circulation time in the body. Each component in an LNP is selected for specific purposes—whether to target immune cells, prevent leakage, avoid aggregation, or boost membrane stability.

Chamberlain’s research focuses on a largely untapped source of novel lipids: bacteria. Specifically, the environmental bacterium Caulobacter crescentus produces unusual sphingolipids, including a previously uncharacterized compound called ceramide phosphoglycerate (CPG). This headgroup modification is not found in other organisms and may bring new properties to synthetic membranes.

Because CPG isn’t commercially available, Chamberlain’s team cultivates Caulobacter in bulk—hundreds of liters at a time—to purify this rare lipid. They then incorporate it into synthetic liposomes for comparison against known sphingolipids, performing a series of physicochemical tests to evaluate its potential as a nanocarrier component.

Two key analyses were highlighted. First, zeta potential measurements showed that while CPG has moderate effects on membrane surface charge compared to POPC and neutral C16 ceramide, ceramide-1-phosphate, a CPG precursor, is more capable of reducing aggregation.  This is important for LNP stability in the bloodstream. Second, Laurdan fluorescence analysis indicated that CPG-containing membranes are more fluid and less densely packed than ceramide-1-phosphate and neutral C16 ceramide, a potentially valuable feature for membrane fusion or dermal delivery.

While the CPG liposomes did not match the high zeta potential or rigidity of their ceramide-1-phosphate counterparts, their unique properties could offer distinct advantages in drug delivery settings where flexibility, biocompatibility, or cell targeting are important.

Chamberlain's work opens the door to a new class of engineered lipid nanoparticles informed by bacterial lipid diversity. With more bacterial sphingolipids from Caulobacter awaiting characterization, his research highlights the exciting potential of microbiology to contribute directly to therapeutic innovation.

See Josh’s talk at: https://youtu.be/VNECL0SaDB0

Stankeviciute G, Tang P, Ashley B, Chamberlain JD, Hansen MEB, Coleman A, D'Emilia R, Fu L, Mohan EC, Nguyen H, Guan Z, Campopiano DJ, Klein EA. Convergent evolution of bacterial ceramide synthesis. Nat Chem Biol. 2022 Mar;18(3):305-312. doi: 10.1038/s41589-021-00948-7. Epub 2021 Dec 30. PMID: 34969973; PMCID: PMC8891067.

https://www.nature.com/articles/s41589-021-00948-7