Fragment-based screening identifies molecules targeting the substrate-binding ankyrin repeat domains of tankyrase.
Pollock K, Liu M, Zaleska M, Pfuhl M, Collins I*, Guettler S*
BioRxiv, 2019, doi: https://doi.org/10.1101/567446
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It all starts with protein purification.
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Science and large rodents ...
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We study the architecture of protein complexes using cryo-electron microscopy.
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We use X-ray crystallography to study protein function in signal transduction.
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TNKS2 SAM domain filaments: some signalling proteins polymerise to switch functional states.
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We aim to reconstitute signalling complexes from purified proteins to recapitulate their activities in the cell.
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Punctate subcellular localisation reflects polymerisation of this signalling protein.
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We use structural and biochemical information to interrogate protein function in cells.
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Happy pipetting!
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We have used X-ray crystallography to reveal the mechanism of tankyrase polymerisation.
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X-ray crystallography provides detailed insights into protein mechanisms.
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Our lab is located at the Chelsea site of ICR in central London. This is the view from the top floor.
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A GPU system for our cryo-EM work: of course the coolant had to be green.
Using Structural Biology to Understand Cell Signalling
Welcome to the Guettler Lab! We employ biochemistry, structural biology and cell biology to study the molecular mechanisms of Wnt/beta-catenin signalling and telomere homeostasis, with a particular focus on how poly(ADP-ribosyl)ation (PARylation) controls both processes. Besides understanding fundamental mechanisms of cell function, we aim to uncover novel potential therapeutic avenues in cancer.Selected Publications
View all »Solution NMR assignment of the ARC4 domain of human tankyrase 2.
Zaleska M, Pollock K, Collins I, Guettler S, Pfuhl M
Biomolecular NMR Assignments, 2019
View on PubMed »Structural Basis for Auto-Inhibition of the NDR1 Kinase Domain by an Atypically Long Activation Segment.
Xiong S, Lorenzen K, Couzens AL, Templeton CM, Rajendran D, Mao DYL, Juang YC, Chiovitti D, Kurinov I, Guettler S, Gingras AC, Sicheri F
Structure (London, England : 1993), 2018, 26 (8), 1101-1115.e6
View on PubMed »Regulation of Wnt/β-catenin signalling by tankyrase-dependent poly(ADP-ribosyl)ation and scaffolding.
Mariotti L, Pollock K, Guettler S
British Journal of Pharmacology, 2017, 174 (24), 4611-4636
View on PubMed »Identifying and Validating Tankyrase Binders and Substrates: A Candidate Approach.
Pollock K, Ranes M, Collins I, Guettler S
Methods in Molecular Biology (Clifton, N.J.), 2017, 1608, 445-473
View on PubMed »Tankyrase Requires SAM Domain-Dependent Polymerization to Support Wnt-β-Catenin Signaling.
Mariotti L, Templeton CM, Ranes M, Paracuellos P, Cronin N, Beuron F, Morris E, Guettler S
Molecular Cell, 2016, 63 (3), 498-513
View on PubMed »AXIN Shapes Tankyrase ARChitecture.
Guettler S
Structure (London, England : 1993), 2016, 24 (10), 1625-1627
View on PubMed »Latest News
View all »Mariola’s paper is published!
Mariola’s paper is published in Biomolecular NMR Assignments: Solution NMR assignment of the ARC4 domain of human tankyrase 2. Congratulations to Mariola and Katie! This has been the first step in an exciting collaboration with Mark Pfuhl and Ian Collins.
New manuscript: first steps in targeting substrate binding of tankyrase
Katie’s manuscript entitled “Fragment-based screening identifies molecules targeting the substrate-binding ankyrin repeat domains of tankyrase” is now available on bioRxiv. A very enjoyable collaboration with Professor Ian Collins at ICR and Dr Mark Pfuhl at King’s College! Thank you and congratulations to the team!
Postdoctoral Position in Cryo-EM and Biochemistry Available
Would you like to join our team? A Wellcome-Trust-funded postdoc position in cryo-EM and Biochemistry is available from April on. For more information and to apply, please visit the ICR Recruitment Portal. Please get in touch if you are interested!
Wellcome Trust Investigator Award to the Lab
Great news just before Christmas: we are delighted to have been awarded a 5-year Wellcome Trust Investigator Award to study molecular mechanisms of telomere maintenance. Watch this space for new postdoc positions in Structural Biology and Telomere Biology!
PhD student Yexin Xie receives Boehringer Ingelheim Fonds Travel Grant
PhD student Yexin has been awarded a Boehringer Ingelheim Fonds Travel Grant to attend the 8th Brazil School for Single-Particle Cryo-EM. Many congratulations to Yexin, and many thanks to the Boehringer Ingelheim Fonds!
Welcome Iona and Sam!
Today we welcome two new PhD students to our team: Iona Black and Sam Hibbs. Two highly collaborative projects with the Collins and Lord teams at ICR are waiting for them.
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