Modifying membranes with mycolic acids – models, and experiments to understanding properties of unusual lipid functionality
Lab rotation project description
This project will offer three lab rotations; one per partner.
Rotations will be offered by each partner:
This rotation project will develop skills in working with our crowd-sourced world community grid computing environment (in conjunction with IBM) to probe the conformations of a defined set of mycolic acids, in preparation for developing the membrane models.
Training in molecular dynamic simulation, simulation analysis, and bioinformatics relating to structural analysis will be provided as part of this rotation.
School of Life Sciences, Bonev/Chemistry, Hirst
Solid state NMR mini-project: The objective is to give in a nutshell a flavour of the continuity in biological research from design and sample preparation through analysis to functional characterisation.
- Week 1-2: A set of mycolic acid structures will be built in silico and computational predictions of their 13C NMR spectra will be obtained.
- Week 3-4: Model membranes will be prepared form lipid mixtures mimicking mycobacterial membranes and incorporating either synthetic or natural mycolic acids. The membranes will be studied by solid state NMR to obtain a 13C spectrum from the MA.
- Week 5-6: Experimental spectra will be compared to the prediction and used for spectral resonance assignment.
School of Life Sciences, Kovacs
To develop live models, expression systems for mycolic acids will need to be developed. This project will take the early steps in developing appropriate expression systems, taking a systems view of MA production.
Training in synthetic and systems biology techniques will be provided.
Anna Croft – Engineering
Linked PhD Project Outline
Mycolic acids are extremely long-chain (60-90 carbons) fatty acids that are produced by Mycobacteria, Corynebacteria and Norcardia.
They have been identified as strong contributors to the robustness of these organisms, including acting as a barrier to the transport of certain metabolites (including drug molecules) and protecting against external stressors such as damaging reactive oxygen species.