Project Reference: TRG27-BIO-CB1

Project title: Primitive cytoskeletons that drive primitive cell morphogenesis and division

Project outline

Understanding how primitive molecular systems could organise themselves into functional, dividing cells is a central question in origins-of-life research. Membranes provide the boundary that defines cells, but without internal or cortical structures to remodel them, simple vesicles cannot robustly change shape or divide. This project will investigate how minimal, prebiotically plausible “cytoskeleton-like” assemblies could control membrane morphology and drive division-like events.

The project combines Dr. Claudia Bonfio’s expertise in prebiotic chemistry, membrane biophysics and protocell engineering with Prof. Laura Machesky’s expertise in actin cytoskeleton dynamics, membrane remodelling and cell division in cancer cells. In the first stage, the student will design and characterise primitive cytoskeletal candidates, including short self-assembling peptides, peptide-RNA condensates and interfacial hydrogels. Using fluorescence microscopy, rheology and biophysical assays, they will identify systems that form filamentous or networked structures at membrane interfaces and generate measurable mechanical forces.

Promising candidates will be reconstituted in short-chain phospholipid-based liposomes as prebiotically relevant protocell models. Time-lapse confocal and super-resolution microscopy will be used to quantify membrane shape changes, including tubulation, invagination, budding and constriction. Fluorescence-based tension sensors, anisotropy measurements and zeta potential analyses will link internal scaffold organisation to changes in membrane packing, curvature and surface charge, defining the physical parameters that enable division-like fission.

Finally, iterative design of peptide/RNA systems, guided by quantitative imaging and simple physical models, will establish minimal design rules for primitive cytoskeletal function.

Principal Supervisor

Dr Claudia Bonfio

Email address: cb2036@cam.ac.uk

Department / Partner Institute: Biochemistry

Website: https://bonfiolab.eu/

BBSRC strategic theme

Understanding the rules of life