Research area
Keeping enzymes working outside water
Doctoral work on random copolymers as synthetic chaperones for enzymes in water-miscible organic solvents, screened on an automated plate-based platform.
Enzymes are extraordinary catalysts in water and frequently useless outside it. Move one into a water-miscible organic solvent, often where the interesting synthetic chemistry happens, and it tends to unfold, aggregate and drop out of solution.
Random copolymers can act as synthetic chaperones, wrapping a protein in a shell whose chemistry is tunable monomer by monomer. The difficulty is that the relationship between that shell's composition and whether the enzyme survives is not obvious from first principles.
How the screen runs
Six monomers combined three at a time, in composition steps, at a handful of chain lengths is already more distinct polymers than anyone screens by hand, and the real space does not come in tidy steps. That is the reason the search runs in parallel rather than one rational design at a time.
The assay, end to end
Each step has to survive being done ninety-six times in parallel without the numbers drifting.
The numbers
| Step | Stage | Detail |
|---|---|---|
| 1 | Synthesise copolymer library | photo-ATRP, one plate |
| 2 | Add enzyme | form polymer–enzyme hybrid |
| 3 | Transfer to organic solvent | water-miscible |
| 4 | Read solubility | plate reader |
| 5 | Read retained activity | enzyme assay |
| 6 | Model structure–function | on every well, including failures |
Schematic A description of the approach. This work is in preparation; no results are shown.
Two things make this work as a dataset rather than a set of experiments. Every well is measured the same way, and the wells that fail are kept. A polymer that leaves the enzyme insoluble produces a number, and that number is as informative for modelling as a success.
This work is in preparation. No results are shown on this page, and the figures above describe the approach rather than reporting outcomes.
Status
This is ongoing doctoral work and the manuscript is in preparation. If you are working on something adjacent, I would rather talk before it is published than after.