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 »Two Postdoc positions available …
We have two fully funded Postdoc positions available (more details under the links):
(1) Postdoctoral Training Fellow: Cryo-Electron Microscopy and Biophysics/Biochemistry (funded by Cancer Research UK);
(2) Postdoctoral Training Fellow: Cell Biology and Biochemistry of Telomere Function (funded by the Wellcome Trust).
Please get in touch if you would like learn more! Closing date for both is the 25th of August 2019.
Welcome William and Oviya!
Our lab is growing. We welcome Oviya Inian and William (Billy) Fisher into the lab. Oviya is a Postdoctoral Fellow who joins our telomere team. Billy joins us for a two-month summer project funded by a Lister Institute Summer Studentship.
New Postdoc positions coming soon …
Exciting news: our Cancer Research UK Programme Foundation Award application has been successful. New Postdoc positions are coming soon – please stay tuned!
Farewell Pete!
Today we said farewell to Pete. We tried keeping him by narrowly succeeding in the escape room challenge while getting him locked in. With just over two minutes to spare in the end, we did not manage. All the best to Pete in his new adventures!
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!
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!
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