SynthSys

Funding for new strategy to make designer lipids

A new research collaboration led by Professor Dominic Campopiano, School of Chemistry and a member of SynthSys, is one of 14 new projects recently funded via a joint call through the U.S. National Science Foundation (NSF) Directorate for Biological Sciences and the BBSRC.

Prof Campopiano's project, entitled "SynBioSphinx: building designer lipid membranes for adaptive resilience to environmental challenges", will work with Dr Eric Klein (Rutgers) and Prof. Ziqiang Guan (Duke University) in the USA to investigate the use of sphingolipids to make self-contained vesicles. These vesicles could form the basis of synthetic cells that can be programmed to create new healthcare technologies and new ways of replacing environmentally damaging and unsustainable chemical manufacturing methods.

This newly funded collaboration came about when I read Eric's exciting paper published in MBio in April 2019. I immediately contacted him to offer our expertise in sphingolipid research and was glad that he agreed to collaborate. From there we identified the BBSRC/NSF call as a suitable source of funding and are delighted that with this support we can drive this exciting research forward.

Prof Dominic CampopianoSchool of Chemistry 

Sphingolipids (SLs) are key players in human biology, playing an important role as regulators of the inflammatory response. One overarching goal of synthetic biology is to enable the building of synthetic cells in a more predictable and reliable manner. Natural cells generate complex molecules and higher order structures such as the cell membrane that acts as a semi-permeable, external lipid barrier. Cells also display an ability to alter their membrane composition in response to environmental changes (e.g. nutrients) and protect the cell from external threats (e.g. toxins, viruses).

Previous work focused on membranes formed from simple phospholipids but Prof Campopiano’s SynBioSphinx project will study SLs found in eukaryotic cell membranes and an increasing number of important microbes. Eukaryotic SL enzymes are membrane bound and this has hampered the in vitro synthesis of SL-containing vesicles. The team will address this challenge using soluble bacterial enzymes from the SL-producing Caulobacter crescentus to assemble the core SLs.

In Edinburgh, the team will use a series of isolated biocatalysts to direct the synthesis of SLs in vitro and monitor their ability to form vesicles. Dr Eric Klein will use screening strategies (bacteriophage sensitivity and antibiotic resistance) to identify novel SL enzymes. Prof Campopiano and Ziqiang Guan will then use mass spectrometry to track the incorporation of labelled lipids into bacterial membranes and SLs. Edinburgh’s Genome Foundry will assemble gene constructs to direct SL synthesis in vitro.

The research grant from UKRI is worth over £350,000.

You can read more about the new awards here.

https://bbsrc.ukri.org/news/research-technologies/2020/bilateral-agreement-supports-new-research-awards-on-bioinformatics-microbiomes-and-synthetic-biology/