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New ways to control reservoir formation in ultra-low surface tension biological membranes mimics of lung surfactants


Project Description

This PhD project aims to develop new strategies to address low levels of lung surfactant protein B (SPB) in premature babies born with infant respiratory distress syndrome (IRDS). Babies born with low levels of SPB cannot breathe unaided, and IRDS is now the single most common cause of death in the first month of life in the developed world. As background, lung surfactant consists mainly of phospholipids, which lower the surface tension of the air/water interface, while the role of SPB is to nucleate phospholipids reservoirs attached to the surface monolayer during breathing and prevent alveolar collapse. A common and rather crude treatment currently for IRDS is derived from the lungs of animals, but these formulations have their limitations, and more effective therapies are urgently required to improve survival rates. The project combines the use of laser and neutron reflectometry techniques to develop new ways to control the formation of phospholipid reservoirs in ultra-low surface tension biological membranes that mimic lung surfactant, as well as design and test new synthetic particles to mimic the behaviour of SPB. A focus is to resolve the structure, morphology and dynamics of the reservoirs, and work will start on bridging the gaps in behaviour between (1) model membranes in the presence of short peptide sequences of SPB and (2) formulations that are used clinically. Monitoring and characterisation of reservoir structures in ultra-low surface tension systems will be performed using a powerful combination of surface-sensitive techniques that has not been applied to the problem before. Laser reflectometry equipment and Langmuir troughs have been newly set up in the Lawrence-Campbell surface science lab, and applications for neutron beam time will be made to enrich the insight gained from the laboratory data. The successful candidate will be enrolled in the doctoral program at the University of Manchester.

Applicants are expected to hold, or about to obtain, a minimum upper second class undergraduate degree (or equivalent) in chemistry, physical chemistry, physics, pharmacy or pharmaceutical sciences. A Masters degree in a relevant subject area would be advantageous.

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor.

Funding Notes

Salary award for 3.5 years and fees are underwritten at band 0/ standard level for UK/EU students by the Division of Pharmacy and Optometry. Divisional support will contribute also to the consumables and conference/workshop attendance for the student. Details of our different fee bands can be found on our website (View Website)

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

Tummino, A.; Toscano, J.; Sebastiani, F.; Noskov, B. A.; Varga, I.; Campbell, R. A. Langmuir, 2018, 34, 2312–2323.
Campbell, R. A.; Tummino, A.; Varga, I.; Milyaeva, O. Y.; Krycki, M. M.; Lin, S.-Y.; Laux, V.; Haertlein, M.; Forsyth, V. T.; Noskov, B. A. Langmuir, 2018, 34, 5020–5029.
Braun, L.; Uhlig, M.; von Klitzing, R.; Campbell, R. A. Adv. Colloid Interface Sci., 2017, 247, 130–148.
Parra, E.; Perez-Gil, J. Chemistry and Physics of Lipids, 2015, 185, 153–175.
Krafft, M. P. Soft Matter, 2015, 11, 5982–5994.

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