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Multiscale Simulations of Droplet-Membrane Mutual Remodelling

  • Full or part time
  • Application Deadline
    Friday, March 06, 2020
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Applications are invited for a fully funded PhD studentship as part of the MoSMed CDT which is run jointly with Newcastle University. The supervisory team comprises Dr Halim Kusumaatmaja (Durham), Dr Agnieszka Bronowska (Newcastle), Dr Roland Knorr, (MPI Colloids and Interfaces), and Prof Wolfram Antonin (RWTH Aachen).

Phase separation is a familiar concept in the physical sciences, ranging from the common observation of water and oil demixing, to its use to create advanced materials for food, energy and photonic applications. In cellular biology, intracellular phase separation has garnered much attention recently as a means to organise intracellular solutions through the formation of droplet-like sub-compartments [1]. Examples of such droplet compartments include the stress granules and P-bodies.

Key to this project is that these droplets interact with membranes, and as a result, the droplets and the membranes can mutually remodel their shapes and morphologies [2]. For example, during autophagy, membrane sheets remodel into double-membrane organelles called autophagosomes. Autophagosomes can selectively isolate cargoes for elimination, including harmful cytosolic droplets [3]. In fact, numerous physiological processes have been identified with similar membrane morphologies, suggesting that these droplet-membrane interactions are a general cellular mechanism.

The aim of this interdisciplinary project is to develop the much-needed understanding of these droplet-membrane interactions, and their mutual remodelling during droplet isolation. Here, we will use a multiscale modelling approach. At the molecular level, we will employ molecular dynamics simulations to study the formation of the droplets via a liquid-liquid phase separation mechanism and the affinity between the droplet and membrane. These results will inform a continuum modelling approach based on elasticity theory for studying the droplet and membrane shapes. The theoretical/computational work by the student will also provide an important framework to rationalise and guide ongoing in vitro and in vivo experiments. Our long-term goal is to provide new insights into processes inside cells exploiting this novel physical mechanism based on droplet-membrane interactions.

Applying for the Position
The closing date for applications is Friday 6th March 2020. Interviews will take place week commencing 16th March 2020. The start date is October 2020 as part of Cohort 2 of EPSRC Centre for Doctoral Training (CDT) in Molecular Sciences for Medicine (MoSMed). Applicants should have a good first degree in physics or related subjects, e.g. biophysics, computational chemistry, computational biology, etc. Informal enquiries are welcome and should be addressed to Dr. Halim Kusumaatmaja ().

To apply for this project please visit the Durham University application portal to be found at: https://www.dur.ac.uk/study/pg/apply/. Please select the course code F1A201 for a PhD in Molecular Sciences for Medicine and indicate the reference MoSMed20-13 in the ‘Field of Study’ section of the application form. Should you have any queries regarding the application process at Durham University please contact the Durham MoSMed CDT Manager, Emma Worden at: .

Further details about MoSMed CDT can be found at https://research.ncl.ac.uk/mosmed/, and about Dr Kusumaatmaja’s group at https://sites.google.com/site/kusumaatmaja.





Funding Notes

Full funding is available to UK/EU students for 4 years.

References

References
[1] Y. Shin and C. P. Brangwynne, Science 357, eaaf4382 (2017).
[2] H. Kusumaatmaja and R. Lipowsky, Soft Matter 7, 6914 (2011).
[3] Y. Fujioka et al., Nature 578, 301-305 (2020).

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