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.

  • A foggy day in London Town.

    A foggy day in London Town.

  • 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.

  • Our neighbours: the Natural History and Victoria & Albert Museums.

    Our neighbours: the Natural History and Victoria & Albert Museums.

  • Weiter forschen - keep researching!

    Weiter forschen - keep researching!

  • Cryo-EM map of a tankyrase filament.

    Cryo-EM map of a tankyrase filament.

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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Structural basis of tankyrase activation by polymerization.

Pillay N, Mariotti L, Zaleska M, Inian O, Jessop M, Hibbs S, Desfosses A, Hopkins PCR, Templeton CM, Beuron F, Morris EP, Guettler S

Nature, 2022

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Reconstitution of the destruction complex defines roles of AXIN polymers and APC in β-catenin capture, phosphorylation, and ubiquitylation.

Ranes M, Zaleska M, Sakalas S, Knight R, Guettler S

Molecular Cell, 2021

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ADP-ribosyltransferases, an update on function and nomenclature.

Lüscher B, Ahel I, Altmeyer M, Ashworth A, Bai P, Chang P, Cohen M, Corda D, Dantzer F, Daugherty MD, Dawson TM, Dawson VL, Deindl S, Fehr AR, Feijs KLH, Filippov DV, Gagné JP, Grimaldi G, Guettler S, Hoch NC, Hottiger MO, Korn P, Kraus WL, Ladurner A, Lehtiö L, Leung AKL, Lord CJ, Mangerich A, Matic I, Matthews J, Moldovan GL, Moss J, Natoli G, Nielsen ML, Niepel M, Nolte F, Pascal J, Paschal BM, Pawłowski K, Poirier GG, Smith S, Timinszky G, Wang ZQ, Yélamos J, Yu X, Zaja R, Ziegler M

The FEBS Journal, 2021

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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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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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01/12/2023

Lab day out in the Surrey Hills

This year’s lab trip took us to the Surrey Hills, where we enjoyed autumn colours, beautiful views, friendly bovines and glorious mud. The best scientific ideas are not born at the desk.

01/12/2023

Welcome Nafis and Katy!

This summer and autumn, we welcomed two new lab members: Nafiseh Chalabi Hagkarim joins us as a Postdoctoral Fellow, and Katy Miller is embarking on her PhD. Welcome Nafis and Katy!

27/11/2023

Sebastian delivers inaugural lecture

On the 24th of November, Sebastian delivered his inaugural lecture at the ICR, titled “Encoding the Language of Signalling Proteins” – a great occasion for colleagues, team members, mentors, friends and family to convene and celebrate! Thank you to everyone who came!

01/09/2023

Summer Science

This summer, we welcomed two students to our lab. Dylan Clements learned about the daily lives of biochemists and structural biologists during his week-long stay. Sofia Savastano spent a seven-week Lister-Institute funded Summer Studentship with us, joining forces with Matt to have fun with tankyrase.

16/08/2023

Barcelona!

Ben, Saira and Sebastian presented the latest of the lab’s Wnt signalling work at this year’s Gordon Research Seminar and Conference in Barcelona. Ben spoke at the Gordon Research Seminar, and both Ben and Saira presented a poster at the Conference. A fantastic week of science and connecting with old and new friends in the field!

15/06/2023

Welcome Raj!

Keerthiraju Ravichandran joins us as a Postdoctoral Fellow after completing his PhD in the Max Planck Research Group at the Malopolska Centre of Biotechnology in Krakow, Poland. Welcome Raj!

15/06/2023

Congratulations, Muhammed!

Congratulations to Muhammed Kocak, who has successfully defended his PhD thesis!

03/02/2023

Michael launches his research lab

Last December, we said farewell to Michael Ranes, Postdoctoral Fellow in our team. Funded by Wellcome, Michael has now launched his own research lab at the University of Oxford, where he will study Wnt/beta-catenin signalling mechanisms. Congratulations Michael!

24/11/2022

Cryo-EM reveals structural basis of tankyrase activation by polymerisation

In our latest paper, we report structure-function studies that reveal how tankyrase is turned from a sluggish to an active protein by filamentous polymerisation. You can read the open-access paper here. The paper comes with a press release by ICR. Congratulations to the team!

17/10/2022

Welcome Shafayat!

We welcome Shafayat Azad to our team. Shaf joins us as a PhD Student and will investigate the mechanisms of telomere maintenance.

10/10/2022

Michael speaks at “Black in Cancer”

Michael Ranes speaks at the inaugural “Black in Cancer” conference – an international collaboration between Black in Cancer and Cancer Research UK, one of our major funders.

10/10/2022

Team Member Yexin Xie receives her PhD

Last month, we celebrated Yexin’s PhD graduation. Many congratulations Yexin on your well-deserved PhD, and all the best for your next steps!

26/09/2022

Thank you and goodbye to Nisha!

After almost three years in the lab, Nisha is moving on. We say thank you and goodbye – all the best for the future! Stay tuned for exciting publication news coming soon.

26/09/2022

Farewell Euan!

We say thank you and farewell to Euan Colaco Osorio, who joined us for almost two months as a Summer Student funded by the Lister Institute. All the best for your next adventure!

26/09/2022

Iona awarded poster prize at American Chemical Society Medicinal Chemistry Symposium

PhD Student Iona Black has has been awarded the Best Poster prize at the 37th American Chemical Society Medicinal Chemistry Symposium held in New York City in June 2022. To attend the conference, Iona received a Royal Society of Chemistry researcher development grant of £500. Many congratulations Iona!

16/06/2022

2022 Lab Retreat in Hastings

Our first lab retreat in a long time: two days of science and sunshine … and lots of food.

30/12/2021

Destruction complex reconstitution among ten featured ICR achievements of 2021

Our reconstitution of the beta-catenin destruction complex made it to ICR’s ten featured scientific achievements of 2021. What a nice way to end the lab year and a real testament to the team’s work! You can find all research highlights on the ICR website.

29/10/2021

#BlackinCancer: Reaching communities most affected by prostate cancer

For Black in Cancer Week, ICR’s Science Communications Officer Juanita Bawagan spoke to our team member Dr Michael Ranes about the importance of diversity in cancer research for science and society. You can read the article here.

22/09/2021

Michael speaks at the UNC Cancer Network

Our Postdoc Michael Ranes will present his work at the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center. Here are the seminar details:

“Molecular mechanisms of Wnt signaling: reducing complexity”.
https://unccn.zoom.us/webinar/register/WN_2oM9nhM8Sz-xBL9QgGuXCg/
Sep 22, 2021 11:00 AM in Eastern Time (US and Canada)

01/09/2021

Our latest paper hits the ICR news.

The ICR has featured our latest paper in its news stream on the ICR website.

04/08/2021

New paper: biochemical reconstitution of the beta-catenin destruction complex

Our latest paper, reporting the biochemical reconstitution of the beta-catenin destruction complex, is now published online. Congratulations to Michael, Mariola, Saira and Ruth! You can find the open access article here.

04/12/2020

ICR survey gives insight into the impact of the COVID-19 pandemic on cancer research

The Institute of Cancer Research surveyed 239 of its researchers to gain insights into the impact of the COVID-19 pandemic on their research, and to point to possible solutions. Read the results here.

02/12/2020

New electron microscopy infrastructure

Exciting news: our new Glacios cryo-electron microscope has arrived and is being installed. The photo pictures Basil Greber, a new Team Leader in the Division of Structural Biology, with the microscope in its new home. A new era of Structural Biology at the ICR!

Affiliations

Support

Cancer Research UK
The Lister Institute of Preventive Medicine
The Institute of Cancer Research
Wellcome Trust
The Masonic Charitable Foundation
UKRI MRC
iNEXT Discovery