ComeInCell Doctoral Network PhD Studentship: Sculpting synthetic cell membranes with co-transcriptional RNA condensates

This PhD position is offered through the ComeInCell European MSCA Doctoral Network. More details about PhD projects offered through the ComeInCell Program can be found here: https://www.comeincell.org/projects

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

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)

General Application Information
Funding information:
Funding agency: H2020-MSCA-ITN-2023 (Project Nr: 101168939)

Doctoral Candidate (DC) Allowances:
MSCA Doctoral Networks provide attractive salary terms and benefits, including a living allowance of around €3,400 (country correction coefficient applies), a mobility allowance of €600 and, a family allowance (€660 if applicable). Note that these are gross values and employer costs or other deductions depend on the recruiting host.

Mobility Conditions:
MSCA networks require that applicants must not have resided or carried out their main activity (work, studies, etc.) in the country of the recruiting organisation for more than 12 months in the 36 months immediately before their recruitment date.

The individual scientific projects are planned within one of the partner Host Institution and every doctoral candidate will spend a part of their doctoral studies in another partner laboratory (a maximum of 12 months of their 36 months PhDs).

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.

Starting Date:
All projects will commence preferably within the first half of 2025, depending on the host institution. Contact the corresponding PIs for more details.

Candidate Specification

Qualifications
Essential: 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

Desirable: Practical experience with model membranes and/or nucleic acid nanotechnology

Knowledge and Experience
Essential: Research project carried out in at least one of the above disciplines, programming Skills (Python or Matlab), a demonstrated knowledge of at least one of the following: nucleic acid nanotechnology, membrane biophysics, biophysics of biomolecular condensates

Desirable: Microscopy experience (optical, confocal)

Skills and Competencies
Essential: Scientific writing (LaTex)

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