Unravelling animal African trypanosomiasis: starve the parasite, feed the world
Lead Research Organisation:
University of Nottingham
Department Name: School of Life Sciences
Abstract
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Organisations
People |
ORCID iD |
| Catarina Gadelha (Primary Supervisor) |
Publications
Henry Miller T
(2024)
Sorting of GPI-anchored proteins at the trypanosome surface is independent of GPI insertion signals.
in Cell surface (Amsterdam, Netherlands)
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M008770/1 | 30/09/2015 | 31/03/2024 | |||
| 1645207 | Studentship | BB/M008770/1 | 30/09/2015 | 29/09/2019 |
| Description | Epithelial cells of complex organisms are able to sort some glycosylphosphatidylinositol (GPI)-anchored proteins to either the basolateral or apical domain of the plasma membrane, and the GPI anchor itself has been shown to play a role in this. Unicellular protozoan parasites like Trypanosoma brucei have also specialised their plasma membrane into subdomains, but it remains unknown what protein sorting mechanism is in place here. We have used 5 model proteins that are anchored to the trypanosome membrane via GPI to ask if their lipid moiety is involved in protein targeting to distinct membrane domains. Initial results have showed that not to be the case. However, results also showed that (GPI)-anchored protein sorting in T. brucei may not be as simple as previously thought and that the amino acids near to the GPI-attachment site influence protein processing. Recombinant protein technology has widespread application in biology and medicine. Many protein expression systems exist, but each with its limitations and benefits. To study Trypanosome brucei parasites, an efficient and evolutionary-related expression system is desirable. We are currently developing the related trypanosomatid Crithidia fasciculata for T. brucei recombinant protein production because of its fast and high-density growth capacity. We have genetically engineered C. fasciculata to switch recombinant protein expression ON and OFF via the addition of a specific antibiotic to the culture medium. Optimisation steps, including the testing of multiple DNA processing sequences, have led to the production of high levels of the reporter protein GFP. Further experiments have attempted to asses and optimise the system's ability to express a variety of T. brucei proteins to high levels for further study and characterisation, with some success. Ultimately, this system may prove a useful tool for particular biochemical applications, however, further improvements and characterisation will broaden its applicability. |
| Exploitation Route | Overall, the project investigating protein sorting mechanisms has laid the groundwork for further study of (GPI)-anchored proteins in T. brucei, enabling greater understanding of this clinically relevant parasite. With further development, our heterologous expression system will be extensively used in our laboratory and those of collaborators. We anticipate it to be useful not only for the production of recombinant trypanosome proteins but also those from other human pathogens and eukaryotic cells in general. |
| Sectors | Agriculture Food and Drink Healthcare |
| Description | Society conference grant |
| Amount | £90 (GBP) |
| Funding ID | GA000279 |
| Organisation | Microbiology Society |
| Sector | Learned Society |
| Country | United Kingdom |
| Start | 03/2018 |
| End | 04/2018 |