Liposome delivery to the placenta -artificial extracellular vesicles astherapy for preeclampsia/IUGR (Dr Manu Vatish)
Liposome delivery to the placenta -artificial extracellular vesicles astherapy for preeclampsia/IUGR
DESCRIPTION OF PROJECT
Extracellular vesicles permit intercellular communication between cells. In pregnancy, these can travel between the placenta and maternal organs and vice versa. We wish to capitalize on data already gained examining the phenotype of syncytiotrophoblast extracellular vesicles (STBEV), and use the knowledge gained to target artificial EVs (liposomes) delivery to the placenta. We believe that mimicking the natural targeting systems to the placenta will enable directed therapies for placental diseases such as preeclampsia and intrauterine growth restriction,
This project will aim to synthesize liposomes decorated with placenta targeting proteins (identified by proteomics analysis of STBEV). These liposomes will be furnished with cargoes aimed at improving placental function (e.g. nutrients) or decreasing placental pathology (e.g. siRNA).
Assessment of efficacy will be performed both functionally (hormone assays, ATP production) as well as transcriptionally (deep sequencing). These data will be bioinformatically analysed to assess global changes in placental function. Successful therapeutic moieties will be further assessed in animal models.
- Placental characterization and placental perfusion (to harvest native STBEV)
- Liposome synthesis and protein incorporation.
- Placental explants and cell lines
- Assessment of liposome uptake (ELISAs, hormone assays, ATP/energy assessment, imaging)
- Bioinformatics based selection of cargo
- Placental explants and cellular treatments
- Functional assessments of placental function
- Transcriptomic assessment and bioinformatics
- Assessment of effects in normal and diseased states
- Key targets for further characterization in animal models
- General molecular biology
- Flow cytometry, nanoparticle tracking analysis etc.
As well as the specific training detailed above, students will have access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford.