The Guettler Lab

Divisions of Structural Biology and Cancer Biology

The Institute of Cancer Research

  • It all starts with protein purification.

    It all starts with protein purification.

  • Science and large rodents ...

    Science and large rodents ...

  • We study the architecture of protein complexes using cryo-electron microscopy.

    We study the architecture of protein complexes using cryo-electron microscopy.

  • We use X-ray crystallography to study protein function in signal transduction.

    We use X-ray crystallography to study protein function in signal transduction.

  • TNKS2 SAM domain filaments: some signalling proteins polymerise to switch functional states.

    TNKS2 SAM domain filaments: some signalling proteins polymerise to switch functional states.

  • We aim to reconstitute signalling complexes from purified proteins to recapitulate their activities in the cell.

    We aim to reconstitute signalling complexes from purified proteins to recapitulate their activities in the cell.

  • Punctate subcellular localisation reflects polymerisation of this signalling protein.

    Punctate subcellular localisation reflects polymerisation of this signalling protein.

  • We use structural and biochemical information to interrogate protein function in cells.

    We use structural and biochemical information to interrogate protein function in cells.

  • Happy pipetting!

    Happy pipetting!

  • We have used X-ray crystallography to reveal the mechanism of tankyrase polymerisation.

    We have used X-ray crystallography to reveal the mechanism of tankyrase polymerisation.

  • X-ray crystallography provides detailed insights into protein mechanisms.

    X-ray crystallography provides detailed insights into protein mechanisms.

  • Our lab is located at the Chelsea site of ICR in central London. This is the view from the top floor.

    Our lab is located at the Chelsea site of ICR in central London. This is the view from the top floor.

  • A GPU system for our cryo-EM work: of course the coolant had to be green.

    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

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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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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

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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

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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

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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

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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

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AXIN Shapes Tankyrase ARChitecture.

Guettler S

Structure (London, England : 1993), 2016, 24 (10), 1625-1627

View on PubMed »

Latest News

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07/03/2019

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!

19/02/2019

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!

22/12/2018

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!

05/11/2018

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!

01/10/2018

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.

Affiliations

Support

Cancer Research UK
The Lister Institute of Preventive Medicine
The Institute of Cancer Research
Wellcome Trust