Dr Paola Vergani
Cystic fibrosis is the most common life-threatening inherited disease in the UK. We study the protein whose dysfunction causes cystic fibrosis, CFTR. This same protein is responsible for the excessive salt/water loss occurring during secretory diarrhoeas (e.g. cholera). CFTR belongs to the superfamily of ABC proteins, which couple hydrolytic cycles at conserved nucleotide-binding domains (NBDs) to diverse cellular functions. CFTR is unique among ABC proteins in that its transmembrane domains comprise an ion channel. Opening and closing (gating) of the ion-permeation pathway is "remotely" controlled by ATP binding and hydrolysis at its NBDs . With our experiments we aim at deepening our understanding of how CFTR works, setting foundations for pharmacological alteration of its activity. In addition, by allowing us to uniquely track conformational changes affecting the ion-permeation pathway, our CFTR studies may help better understand conserved ABC mechanisms.
Quantitative approaches to investigate Cystic Fibrosis
Quantitative approaches to probe CFTR channel opening and closing
Since 2006, I have contributed to undergraduate teaching for BSc students on several physiology and pharmacology modules, and since 2010 I have been tutoring to first year Medical School students.
Since 2009, I am programme tutor for BSc and IBSc in Physiology and Pharmacology.
Prof Stephen Hart; Dr Vivek Dua; Prof David Selwood; Dr Guy Moss
Dr László Csanády
- Vergani P, Gadsby D, Csanády L (2013). CFTR, an Ion Channel Evolved from an ABC Transporter. In Roberts GK (Ed.), Encyclopedia of Biophysics (pp. 254 - 265). : Springer Berlin Heidelberg. doi:10.1007/978-3-642-16712-6_364
- O'Donoghue DL, Dua V, Moss GW, Vergani P (2013). Increased apical Na+ permeability in cystic fibrosis is supported by a quantitative model of epithelial ion transport.. J Physiol, , - . doi:10.1113/jphysiol.2013.253955
- Csanády L, Mihályi C, Szollosi A, Töröcsik B, Vergani P (2013). Conformational changes in the catalytically inactive nucleotide-binding site of CFTR.. J Gen Physiol, , - . doi:10.1085/jgp.201210954
- Corradi V, Vergani P, Tieleman DP (2013). Molecular Models of the Closed State of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).
- Csanády L, Vergani P, Gulyás-Kovács A, Gadsby DC (2011). Electrophysiological, biochemical, and bioinformatic methods for studying CFTR channel gating and its regulation.. In (Ed.), (pp. 443 - 469). : . doi:10.1007/978-1-61779-117-8_28
- Szollosi A, Muallem DR, Csanády L, Vergani P (2011). Mutant cycles at CFTR's non-canonical ATP-binding site support little interface separation during gating.. J Gen Physiol, 137(6), 549 - 562. doi:10.1085/jgp.201110608
- Csanády L, Vergani P, Gadsby DC (2010). Strict coupling between CFTR's catalytic cycle and gating of its Cl- ion pore revealed by distributions of open channel burst durations. Proceedings of the National Academy of Sciences of the United States of America, 107(3), 1241 - 1246.
- Szollosi A, Vergani P, Csanády L (2010). Involvement of F1296 and N1303 of CFTR in induced-fit conformational change in response to ATP binding at NBD2.. J Gen Physiol, 136(4), 407 - 423. doi:10.1085/jgp.201010434
- Gadsby DC, Vergani P, Mense M, Chavez LA, Nairn A (2010). CONTROL OF CFTR'S GATES BY ATP BINDING AND HYDROLYSIS. PEDIATR PULM, , 114 - 115.
- Muallem D, Vergani P (2009). ATP hydrolysis-driven gating in cystic fibrosis transmembrane conductance regulator.. Philos Trans R Soc Lond B Biol Sci., 364(1514), 247 - 255.
- Gadsby DC, Vergani P, Csánady L (2006). The ABC protein turned chloride channel whose failure causes cystic fibrosis.. Nature, 440(7083), 477 - 483. doi:10.1038/nature04712
- Mense M, Vergani P, White DM, Altberg G, Nairn AC, Gadsby DC (2006). In vivo phosphorylation of CFTR promotes formation of a nucleotide-binding domain heterodimer. EMBO J, 25(20), 4728 - 4739. doi:10.1038/sj.emboj.7301373
- Liu WR, Vergani P, Gadsby DC (2005). Investigation of the molecular identity of CFTR channels in cardiac myocytes.
- Vergani P, Lockless SW, Nairn AC, Gadsby DC (2005). CFTR channel opening by ATP-driven tight dimerization of its nucleotide-binding domains.. Nature, 433(7028), 876 - 880. doi:10.1038/nature03313
- Vergani P, Basso C, Mense M, Nairn AC, Gadsby DC (2005). Control of the CFTR channel's gates.. Biochemical Society Transactions, 33(Pt 5), 1003 - 1007.
- Vergani P, Lockless SW, Nairn AC, Gadsby DC (2005). Opening/closing of the CFTR Cl- channel is linked to dynamic dimerization/dissociation of its two nucleotide binding domains.
- Mense M, Vergani P, White DM, Altberg G, Nairn AC, Gadsby DC (2004). Sulfhydryl-specific crosslinking establishes Rad50-like interactions between NBD1 and NBD2 in CFTR chloride channels.
- Vergani P, Naim AC, Gadsby DC (2004). Mutant cycle analyses in CFTR establish role of NBD1/NBD2 dimer in Cl- channel gating.
- Vergani P, Nairn AC, Gadsby DC (2003). On the mechanism of MgATP-dependent gating of CFTR Cl- channels.. Journal of General Physiology, 121(1), 17 - 36. doi:10.1085/jgp.20028673
- Vergani P, Nairn AC, Gadsby DC (2003). Role of electrostatic forces at putative NBD dimer interface in CFTR Cl- channel gating..
- Basso C, Vergani P, Nairn AC, Gadsby DC (2003). Prolonged nonhydrolytic interaction of nucleotide with CFTR's NH2-terminal nucleotide binding domain and its role in channel gating.. Journal of General Physiology, 122(3), 333 - 348. doi:10.1085/jgp.200308798
- Vergani P, Basso C, Nairn AC, Gadsby DC (2002). Effects on CFTR Cl- channel gating of Walker A lysine mutation K464A imply allosteric interaction between NBDS. BIOPHYS J, 82(1), 240A - 240A.
- Basso C, Vergani P, Nairn AC, Gadsby DC (2002). NBD1 might remain nucleotide-bound throughout CFTR channel gating. BIOPHYS J, 82(1), 12A - 12A.
- Mense M, White DM, Vergani P, Nairn AC, Gadsby DC (2002). Generation, expression, and function of cysteine-less CFTR. J GEN PHYSIOL, 120(1), 25A - 25A.
- Vergani P, Basso C, Csanady L, Kopsco D, Sanchez R, Sali A, Nairn AC, Gadsby DC (2001). Roles of ATP binding and hydrolysis in CFTR Cl- channel gating. BIOPHYS J, 80(1), 354A - 354A.
- Csanady L, Chan KW, Seto-Young D, Vergani P, Nairn AC, Gadsby DC (2000). Single-channel and biochemical characterization of severed CFTR channels. BIOPHYS J, 78(1), 467A - 467A.
- Vergani P, Basso C, Csanady L, Kopsco D, Sanchez R, Sali A, Nairn AC, Gadsby DC (2000). Mutations near the predicted catalytic site of NBD1 in CFTR subtly affect Cl- channel function. J GEN PHYSIOL, 116(1), 13A - 13A.
- Vergani P, Csanady L, Basso C, Sanchez R, Naim AC, Gadsby DC (2000). Mutations near the predicted catalytic site of NBD1 affect CFTR CF channel function surprisingly little. BIOPHYS J, 78(1), 264A - 264A.
- Blatt MR, Vergani P, Geelen D, Leyman B (2000). Regulation of K+ channels in higher-plant models. J PHYSIOL-LONDON, 525, 28S - 28S.
- Vergani P, Blatt MR (1999). Mutations in the yeast two pore K+ channel YKC1 identify functional differences between the pore domains.. FEBS Lett, 458(3), 285 - 291.
- Vergani P, Hamilton D, Jarvis S, Blatt MR (1998). Mutations in the pore regions of the yeast K+ channel YKC1 affect gating by extracellular K+.. EMBO J, 17(24), 7190 - 7198. doi:10.1093/emboj/17.24.7190
- Vergani P, Miosga T, Jarvis SM, Blatt MR (1997). Extracellular K+ and Ba2+ mediate voltage-dependent inactivation of the outward-rectifying K+ channel encoded by the yeast gene TOK1.. FEBS Lett, 405(3), 337 - 344.
- Vergani P, Morandini P, Soave C (1997). Complementation of a yeast delta pkc1 mutant by the Arabidopsis proteinANT.. FEBS Lett, 400(2), 243 - 246.
- MARRE MT, VERGANI P, ALBERGONI FG (1993). RELATIONSHIP BETWEEN FUSARIC ACID UPTAKE AND ITS BINDING TO CELL STRUCTURES BY LEAVES OF EGERIA-DENSA AND ITS TOXIC EFFECTS ON MEMBRANE-PERMEABILITY AND RESPIRATION. PHYSIOL MOL PLANT P, 42(2), 141 - 157.