Sculpting synthetic cell membranes with co-transcriptional RNA condensates (DC17)

Hosted by:
Lorenzo Di Michele
University of Cambridge, UK
Department of Chemical Engineering and Biotechnology
dimichelelab.org


Project Specification

Project Summary

We have recently developed technologies to produce synthetic RNA condensates with prescribed number, size, shape, composition, material properties and the ability to selectively recruit protein clients. These condensates form co-transcriptionally in synthetic cells. With this project, we aim to engineer interactions between the synthetic RNA condensates and synthetic cell membranes to induce controlled membrane deformation, patterning and division-like behaviours. Condensate/membrane affinity can be programmed using electrostatics or specifically with either amphiphilic nucleic acid linkers or aptamers targeting membrane proteins. Specific objectives include: 1) Build synthetic cells that can express RNA condensates with controlled affinity for the membrane; 2) Exploit processes such as condensate growth, degradation and internal phase separation to deform and manipulate the membranes (e.g. stabilizing non-spherical morphologies; controlling lipid domain formation, size and distribution; inducing membrane rupture or membrane fission).

The project involves secondments at the Max Plank Institute of Biochemistry (Munich, Germany) in the group of Prof. Petra Schwille and at Imperial College London in the group of Dr Claudia Contini.

Selected References

  • Fabrini, G., Farag, N., Nuccio, S.P. et al. Co-transcriptional production of programmable RNA condensates and synthetic organelles. Nat. Nanotechnol. (2024). https://doi.org/10.1038/s41565-024-01726-x
  • Stewart, J.M., Li, S., Tang, A.A. et al. Modular RNA motifs for orthogonal phase separated compartments. Nat Commun 15, 6244 (2024). https://doi.org/10.1038/s41467-024-50003-x
  • Malouf, L., Tanase, D., Fabrini, G. et al. Sculpting DNA-based synthetic cells through phase separation and phase-targeted activity. Chem 9(11), 3347-3364 (2023)

Standard duties and responsibilities of the DC

For the 36 months of employment contract the doctoral candidate (DC) will be required to work exclusively on the MSCA programme. In all cases, all duties and responsibilities will be clearly outlined in the DC personal Career Development Plan, as determined in the early stages of the project between the DC and their supervisory committee.

Candidate Specification

Qualifications

EssentialDesirable
Applicants should hold or expect to attain, as a minimum MSc degree, or equivalent, with a grade at least equivalent to a UK 2.1 in Physics/Biophysics (preferred), Physical Chemistry, or related engineering disciplines
 
Practical experience with model membranes and/or nucleic acid nanotechnology 

Knowledge and Experience

EssentialDesirable
Experimental research project carried out in at least one of the above disciplinesMicroscopy experience (optical, confocal)
Programming Skills (Python or Matlab)
A demonstrated knowledge of at least one of the following: nucleic acid nanotechnology, membrane biophysics, biophysics of biomolecular condensates

Skills and Competencies

EssentialDesirable
Applicants whose first language is not English or have not completed degrees in English speaking countries must submit evidence of competency in English according to the requirements of the University
Scientific writing (LaTex)

Application

Application details will be published in November 2024!

Further information

For any informal queries, please contact Lorenzo Di Michele by sending an email to ld389 [at] cam.ac.uk

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