I want to join the Hong Kong Laureate Forum to interact with Shaw Laureates and understand their approach to science such that I can hone my skills as an independent scientist. I am particularly looking forward to discussing with Prof. Nogales. Being a structural biologist myself, I am very intrigued by how different PIs approach this field and the implications of the rapid development of bioAI tools such as AlphaFold. Furthermore, I am also very interested in engaging in scientific conversations with different participants. Having studied abroad for most of my scientific career, I would love to have a better understanding of the scientific research ongoing in Hong Kong and the thoughts of local postgraduate students.

The matrix protein 1 (M1) is the most abundant and highly conserved protein found in influenza A viruses. This multifunctional protein mediates nuclear export of the viral ribonucleoprotein complex in its soluble monomeric form, while acting as a scaffolding for viral assembly and budding in its membrane-bound homopolymeric form. Mis-timed conversion from the water-soluble form of M1 to the membrane-bound polymeric form would be detrimental to the virus and must therefore be tightly regulated. Previous work from our laboratory (Mohd-Kipli F. et al. (2021) J Biol. Chem. 296, 100316) hypothesised that conformational changes in loops at the oligomer interface regulate assembly of M1 into the membrane-bound 'stacked' oligomer.

In this study, we confirmed that the M1 N-terminal domain loops exhibit extensive dynamics and conformational exchange in solution across a range of timescales by NMR spectroscopy. Extensive NMR dynamics experiments such as CPMG-RD and CEST reveal complex three-state concentration-dependent dynamics modulated by loop motions. Combined with data from light scattering-based in vitro assay and in vivo single cycle virus data, we propose that M1 loop residues form part of a membrane-binding 'sensor' used by M1 to ensure appropriate polymerisation at the membrane surface.