Fragment-based screening identifies molecules targeting the substrate-binding ankyrin repeat domains of tankyrase.
Pollock K, Liu M, Zaleska M, Meniconi M, Pfuhl M, Collins I, Guettler S
Scientific Reports, 2019, 9 (1), 19130
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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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A foggy day in London Town.
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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.
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Our neighbours: the Natural History and Victoria & Albert Museums.
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Weiter forschen - keep researching!
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 »Welcome Saira, Ben and Giacomo!
In October, we welcomed three new PhD students to the lab: Saira, Ben and Giacomo! Exciting times!
Kick-starting the ICR: an interview with PhD student Iona Black
Iona Black, PhD student in the lab, has been interviewed as part of the #KickstartICR appeal. You can read the interview here. To learn more about how you can help ICR to kick-start research after lockdown, please visit the Kick-Start Appeal website.
Back to the lab …
We are back to the lab since June, with a rotation system to limit occupancy, but our research can go on. Our recent (socially distanced) lab picnic in the nearby Hyde Park was a nice summer treat.
Welcome Lucie, Paul and Matthew!
We recently welcomed three new team members: Lucie Vyletova and Paul Hopkins join us for some time as Higher Scientific Officers. Matthew Jessop started his postdoctoral research. Welcome Lucie, Paul and Matthew!
The team is growing.
Today we welcome our new Postdoctoral Fellow Nisha Pillay to the group. Nisha joins us from the University of Manchester, having studied the molecular determinants of PARG inhibitor sensitivity for her PhD. Welcome Nisha!
Our latest paper is out!
Our latest paper is out: Fragment-based screening identifies molecules targeting the substrate-binding ankyrin repeat domains of tankyrase. Thank you to our collaborators Ian Collins (ICR) and Mark Pfuhl (King’s College London)! Many congratulations to the whole team, in particular first author Katie Pollock on her PhD work! You can read about the work in this ICR press release.
Team member Yexin Xie attends EMBO Course in Practical Integrative Structural Biology
PhD student Yexin Xie has been awarded a place at the EMBO Course “Practical Integrative Structural Biology”. The course takes place at EMBL Hamburg and the Centre for Structural Systems Biology. Congratulations Yexin!
Pathways to Independence and Dean’s Award to Postdoctoral Fellow Michael Ranes
Postdoctoral Fellow Michael Ranes has been awarded a place at the prestigious Pathways to Independence training programme, a joint initiative by the ICR, Sanger, MRC, and Cancer Research UK institutes and the Babraham Institute. The programme provides training for future scientific leaders. Michael has also received a £5,000 Dean’s Award to develop his independent research programme. Congratulations Michael!
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.
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