糖心视频

Personal statement

Ion transport, membrane proteins and bacterial physiology

Life depends on the controlled movement of ions across membranes. In bacteria, this is not simple housekeeping. Ion transport controls nutrient acquisition, pH balance, stress survival, signalling, bioenergetics and adaptation to changing environments. My lab asks how membrane proteins convert a chemical event at the membrane into cellular physiology.

We focus on bacterial membrane transporters, with a major emphasis on the Amt/Mep/Rh superfamily of ammonium transporters. These proteins are ancient, ubiquitous and structurally conserved, yet they support strikingly different biological functions across bacteria, archaea, fungi, plants and animals. In bacteria and plants, they contribute to nitrogen acquisition; in fungi, related Mep proteins can act as nutrient sensors; in animals, Rhesus proteins are linked to ammonium handling, pH homeostasis and physiology. This raises the central biological question in the lab: how can one conserved transporter fold generate such diverse physiological outputs?鹿,鲁,鈦�,鈦�

Our work has helped reshape the mechanistic view of this family. We showed that biological ammonium transport can operate through a two-lane mechanism, in which NH₄⁺ deprotonation is coupled to the separate movement of H⁺ and NH₃ across the membrane.鹿 We then showed that changes in the conserved twin-His motif inside the hydrophobic pazre can switch Amt/Mep/Rh proteins between transporter-like and channel-like behaviour, with consequences for fungal Mep2 transceptor signalling and filamentation.虏 Together, these studies argue that selectivity is not simply encoded by a static filter. Instead, specificity emerges from the chemistry, energetics and dynamics of the transport mechanism itself.鹿,虏,鈦�

We now ask how this molecular mechanism scales up to physiology. How is ammonium transport constrained by thermodynamics and cellular metabolism? How does membrane transport interact with nitrogen assimilation, pH regulation and growth? How do kinetic parameters at the level of a single transporter shape behaviour at the level of the cell? This question is now being extended through systems biology and kinetic modelling, integrating ammonium transport biochemistry with quantitative models of cellular physiology.鈦�

Our experimental approach combines microbial physiology, molecular microbiology, protein biochemistry, membrane-protein functional assays, electrophysiology, phylogenetics, structural biology and computational modelling. Bacteria provide experimentally tractable systems in which we can connect atomic-scale events, pore hydration, proton transfer, substrate binding, conserved residues, lipid interactions and conformational dynamics, to measurable cellular phenotypes.

Recent work in the lab has expanded this programme from mechanism to evolution. We ask how Amt/Mep/Rh proteins diversified from a common ancestral architecture, why different lineages evolved distinct transport or signalling properties, and how changes in pore chemistry, energetic coupling and cellular context produced different biological roles.鲁,鈦�,鈦� This evolutionary perspective allows us to use bacteria not only as model organisms, but also as windows into conserved principles of membrane transport across the tree of life.

More broadly, the lab uses bacterial systems to uncover how membrane proteins transform chemistry into physiology. This work is relevant to microbial nitrogen metabolism, environmental nitrogen cycling, fungal development, biotechnology, membrane-protein engineering and human biology.

Our central question is simple: how do membrane proteins turn ion transport into biological function?

Selected references

1. Williamson, G. et al. A two-lane mechanism for selective biological ammonium transport. eLife 9, e57183 (2020). doi: 10.7554/eLife.57183.
2. Williamson, G. et al. Coexistence of ammonium transporter and channel mechanisms in Amt-Mep-Rh twin-His variants impairs the filamentation signaling capacity of fungal Mep2 transceptors. mBio 13, e02913-21 (2022). doi: 10.1128/mbio.02913-21.
3. Bizior, A., Williamson, G., Harris, T., Hoskisson, P. A. & Javelle, A. Prokaryotic ammonium transporters: what has three decades of research revealed? Microbiology 169, 001360 (2023). doi: 10.1099/mic.0.001360.
4. Williamson, G., Bizior, A., Harris, T., Pritchard, L., Hoskisson, P. A. & Javelle, A. Biological ammonium transporters from the Amt/Mep/Rh superfamily: mechanism, energetics, and technical limitations. Bioscience Reports 44, BSR20211209 (2024). doi: 10.1042/BSR20211209
5. Williamson, G., Harris, T., Bizior, A., Hoskisson, P. A., Pritchard, L. & Javelle, A. Biological ammonium transporters: evolution and diversification. FEBS Journal 291, 3786鈥�3810 (2024). doi: 10.1111/febs.17059.
6. Maeda, K., Kurata, H., Javelle, A., Westerhoff, H. V. & Boogerd, F. C. Computer experimentation on coli ammonium transport and assimilation reveals mechanisms for energy coupling, balanced futile cycling, and robust growth. Preprint at doi: 10.64898/2026.05.09.723968 (2026).

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Key collaborations

Systems biology and kinetic modelling of ammonium transport, Professor Hans V. Westerhoff, Amsterdam, Dr Fred Boogerd, VU Amsterdam, and Professor Toshinari Maeda, Kyushu Institute of Technology. This collaboration combines my expertise in ammonium transport and membrane-protein mechanism with systems biology and kinetic modelling, allowing us to connect transporter biochemistry to cellular physiology. A manuscript from this collaboration is under revision in npj Systems Biology and Applications.

Molecular dynamics of Amt/Mep/Rh transport mechanisms, Professor Ulrich Zachariae, University of Dundee (UK) and Prof Syma Khalid, Universality of Oxford (UK). This collaboration provides atomistic molecular dynamics expertise to model proton transfer, pore hydration, substrate movement and conformational dynamics in ammonium transporters.

Structural biology of bacterial ammonium transporters, Dr Georgia Isom, University of Oxford (UK). This collaboration uses Cryo-EM to obtain structural insight into bacterial Amt/Rh proteins and to link transporter architecture to molecular mechanism.

Native mass spectrometry and lipid-protein interactions, Professor Dame Carol Robinson, University of Oxford (UK). This collaboration investigates how native membrane-protein complexes and lipid interactions influence transporter activity and stability.

Evolution and functional diversification of Amt/Mep/Rh proteins, Dr Leighton Pritchard and Professor Paul A. Hoskisson, 糖心视频 (UK). This collaboration combines comparative genomics, phylogenetics and microbiology to understand how conserved ammonium transporter architectures diversified across evolution.

Evolution of ammonium transport, LUCA and early nitrogen metabolism, Dr Rika Anderson, Carleton College (USA), Dr Joanne Boden, University of Bristol (UK), and Dr Eva St眉eken, University of 听St Andrews (UK). We combine membrane transport, microbial evolution, phylogenomics and early Earth geochemistry. We are developing a synthesis on LUCA relying on environmental ammonium assimilation rather than N₂.

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