Mechanics of retrovirus entry with single molecule microscopy

Sergi Padilla-Parra (primary)
Infectious Diseases
King's College London
Sabrina Simoncelli (secondary)
Chemistry and London Centre for Nanotechnology


Cell entry of retroviruses are mediated by the different subunits of the retroviral envelope glycoprotein (Env) when engaged with cellular receptors. Membrane fusion occurs when the coordinated action of these molecules induces membrane pore formation and opening culminating in capsid release. The molecular determinants regulating murine leukemia virus (MLV) are still elusive. For membrane fusion to occur, the organization of both Env and receptors into micro- and nano-sized protein clusters is crucial. In this project we will employ and further develop state-of-the-art fluorescence microscopy approaches, including fluorescence lifetime imaging microscopy (FLIM) and single-molecule localisation microscopy (SMLM) to address this question.


Coomer CA, Carlon-Andres I, Iliopoulou M, Dustin ML, Compeer EB, Compton AA, Padilla-Parra S.PLoS Pathog. 2020 Single-cell glycolytic activity regulates membrane tension and HIV-1 fusion.
Feb 21;16(2):e1008359. doi: 10.1371/journal.ppat.1008359. eCollection 2020 Feb.PMID: 32084246

A dynamic three-step mechanism drives the HIV-1 pre-fusion reaction.
Iliopoulou M, Nolan R, Alvarez L, Watanabe Y, Coomer CA, Jakobsdottir GM, Bowden TA, Padilla-Parra S.Nat Struct Mol Biol. 2018 Sep;25(9):814-822. doi: 10.1038/s41594-018-0113-x. Epub 2018 Aug 27.PMID: 30150645

Szalai AM, Siarry B, Lukin J, Williamson DJ, Unsain N, Refojo D, Cáceres A, Pilo-Pais M, Acuna G, Owen DM, Simoncelli S, Stefani FD. Three-dimensional total internal reflection fluorescence nanoscopy with sub-10 nm resolution. Nature Communications, 12, 517, 2021.

Simoncelli S, Griffié J, Williamson DJ, Bibby J, Bray C, Zamoyska R, Cope AP, Owen DM. Multi-colour DNA qPAINT reveals how Csk nano-clusters regulate T-cell receptor signalling. Cell Reports, 33, 108523, 2020.

Simoncelli S, Makarova M., Wardley W. and Owen DM. Towards an axial nano-scale ruler for fluorescence microscopy. ACS Nano, 11, 11762-11767, 2017.

Animal disease, health and welfareMolecules, cells and industrial biotechnology
Area of Biology
BiotechnologyCell BiologyChemical BiologyImmunologyMicrobiologyStructural Biology
Techniques & Approaches
BiochemistryBiophysicsImage ProcessingMathematics / StatisticsMicroscopy / ElectrophysiologyMolecular Biology