Synthetic biology of transporters and other enzymes in yeast
Lead Research Organisation:
University of Liverpool
Department Name: Institute of Integrative Biology
Abstract
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People |
ORCID iD |
| Douglas Kell (Principal Investigator) |
| Title | Ergothioneine: the new super antioxidant |
| Description | Scientific animation |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2020 |
| Impact | Created to inform lay as well as professional audiences. |
| URL | https://www.youtube.com/watch?v=SDiYMPpbUpk |
| Title | How drugs and nutrients get into cells |
| Description | Commissioned animation, 3.23 mins long. |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| Impact | The animation was advertised throughout the University of Liverpool using internal communications. It has also been brought to the attention of collaborators across the world. Seeking to understand how drugs and nutrients get into living cells is not how a lot of textbooks portray it. |
| URL | https://youtu.be/s23vNwLE-Jw |
| Description | Experimental approach developed to enable identification of natural substrates of transporters, along with an untargeted metabolomics using LC-HRMS/MS to identify these. This approach uses human cell lines incubated in pooled human serum over a period of time. Untargeted metabolomics analyses using LC Serum in which cells are incubated is then analysed to determine which compounds were changed over time. This has been published: Wright Muelas, M., Roberts, I., Mughal, F. et al. An untargeted metabolomics strategy to measure differences in metabolite uptake and excretion by mammalian cell lines. Metabolomics 16, 107 (2020). https://doi.org/10.1007/s11306-020-01725-8 Above experimental approach has subsequently been applied to 10 x different human cell lines. Untargeted metabolomics data has been acquired and currently being analysed. Membrane protein extracts were also extracted in these experiments and proteomics analyses performed. Initial results show very large differences both in the number of metabolites and in the extent to which these are taken up or excreted by the 10 different human cell lines These large differences are also reflected in transporter protein expression profiles of these cell lines We now seek to correlate these uptake and excretion values to the transcript (obtained from databases) and experimentally observed protein to allow us to infer those variations in transporter expression that best explain the variation in metabolite uptake. |
| Exploitation Route | The approaches developed here can be used to further advance the deorphanisation of transporter substrates. This approach is currently being used in the RESOLUTE consortium: Research Empowerment on Solute Carriers. Here, cell lines overexpressing transporters are used. |
| Sectors | Pharmaceuticals and Medical Biotechnology |
| Description | REsolution - Add Medical Genetic Solutions to ReSolute |
| Amount | € 1,000,000 (EUR) |
| Funding ID | 101034439 |
| Organisation | European Commission H2020 |
| Sector | Public |
| Country | Belgium |
| Start | 05/2021 |
| End | 12/2023 |
| Description | Daye |
| Organisation | Daye |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Member of Medical Advisory Board. Approached to join due to extensive research in the area of the gut microbiome. |
| Collaborator Contribution | The company is developing and optimising intuitive, scientifically robust sexual and reproductive health products. |
| Impact | The company have created and marketed new products. |
| Start Year | 2019 |
| Title | METHODS FOR PRODUCTION OF ERGOTHIONEINE |
| Description | The present invention relates to microbial factories, in particular yeast factories, for production of ergothioneine. Also provided are methods for producing ergothioneine in a yeast cell, as well as useful nucleic acids, polypeptides, vectors and host cells. |
| IP Reference | WO2020221795 |
| Protection | Patent granted |
| Year Protection Granted | 2020 |
| Licensed | No |
| Impact | The present invention relates to microbial factories, in particular yeast factories, for production of ergothioneine. Also provided are methods for producing ergothioneine in a yeast cell, as well as useful nucleic acids, polypeptides, vectors and host cells. Ergothioneine (ERG) (2-mercaptohistidine trimethylbetaine, (2S)-3-(2-Thioxo-2,3-dihydro-1 H-imidazol-4-yl)-2-(trimethylammonio)propanoate) is a naturally occurring antioxidant that can be found universally in plants and mammals; it possess |