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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30/08/2019

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!

18/06/2019

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.

29/03/2019

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!

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!

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!

Affiliations

Support

Cancer Research UK
The Lister Institute of Preventive Medicine
The Institute of Cancer Research
Wellcome Trust
The Masonic Charitable Foundation