Andrew Wood

cell.comOncogene activation mechanism determines the limits of targeted protein degradationGudauskaitė et al. show that the mechanism driving oncogenic protein overexpression influences the effectiveness of targeted protein degradation. While stabilizing mutations do not limit protein deple...

1 Sept

Our latest, out today: “Oncogene activation mechanism determines the limits of targeted protein degradation” www.cell.com/cell-chemica... Work from Evelina's MScR project showing how tumour genetics can impact PROTAC activity

Andrew Wood reposted

🔬 New preprint: How does the mode of oncogene activation shape PROTAC efficacy? Led by Evelina Gudauskaite, we ask whether stabilising mutations vs transcriptional upregulation have distinct consequences for targeted protein degradation. www.biorxiv.org/content/10.6....

This reveals a synthesis dependent ceiling on degradation, with implications for: • interpreting preclinical degrader data • resistance mechanisms • genotype guided therapy design

Most of the experiments were done during Evelina’s Masters project in the lab, and she was brilliantly supervised and supported by Brianda Hernandez Moran and Gillian Taylor.

Our recently published saturation genome editing study characterised mutations which stabilise ß-catenin in cancer: www.nature.com/articles/s41... Less frequently, ß-catenin gets upregulated transcriptionally. Both mechanisms raise protein levels—but do degraders “see” them the same way?

@cp-cellchembiol.bsky.social

Using a controlled cellular system (dTAG + TetOn3G), we found: ✅ Stabilising mutations don’t limit PROTAC action—degradation resets protein levels to the same baseline. ❌ Increased transcription raises target protein levels both pre and post treatment.

Andrew Wood reposted

Biochemical Society

@biochemsoc.bsky.social

14 Apr

Congratulations to Tom Deegan who receives the Colworth Medal in 2027! Pioneering work from the Deegan Lab has redefined our understanding of eukaryotic DNA replication and provided conceptual and technical frameworks that continue to drive new discoveries across molecular biology.

Andrew Wood reposted

Cell Chemical Biology

7 Apr

Online now! Online now! Assessing the suitability of deubiquitylases as substrates for targeted protein degradation #chembiol

dlvr.itAssessing the suitability of deubiquitylases as substrates for targeted protein degradationTong et al. describe a chemical genetic system to evaluate the degradability of deubiquitylase (DUBs) enzymes by PROTACs that do not inhibit their catalytic activity. They find that some Dubs are readily degradable, others resist degradation through auto-deubiquitylation, and some are inherently poor proteasome substrates because they are difficult to unfold.

Today in @natgenet.nature.com, we report a saturation genome editing study that systematically dissects the degron of β-Catenin, which contains 5 of the 25 most frequently mutated regions of the human cancer genome, and >70 recurrent missense mutations. rdcu.be/e1Tvk

...and perhaps most excitingly: - HCC tumours with high effect CTNNB1 mutations tend to be immune excluded, whereas those with low effect mutations do not.

This was a team effort involving effort from many including IGC colleagues @jmarshlab.bsky.social @csemple.bsky.social @ailithewing.bsky.social, @bioggrimes.bsky.social, plus others not on bluesky. Important contributions from Agavni Mesropian and others in the group of Josep M Llovet in Bacelona

Andrew Wood reposted

dbogani.bsky.social

@dbogani.bsky.social

nmgn.mrc.ukri.orgFresh insights reveal how cancer gene mutations drive tumour growth | National Mouse Genetics NetworkScientists have created a comprehensive map showing how hundreds of possible mutations in a key cancer gene influence tumour growth, offering a new insight that could guide the development of […]

An elegant approach using a mix of technologies and making the most of resources generated over many years of research into the canonical Wnt pathway. And results which have the potential to andvance personalised treatment for some forms of cancer. Congrats @andrewwood.bsky.social and collaborators!

MRC National Mouse Genetics Network@mrcmousenetwork.bsky.social

Fresh insights reveal how cancer gene mutations drive tumour growth: Andrew Wood (lead of our Degron Cluster) has co-led a team that created a comprehensive map that shows how hundreds of possible mutations in a key cancer gene influence tumour growth nmgn.mrc.ukri.org/news/fresh-i...

Andrew Wood reposted

Institute of Genetics and Cancer

@uoe-igc.bsky.social

edin.acNew map reveals cancer mutation effects | Institute of Genetics and Cancer | Institute of Genetics and CancerScientists have created a complete map showing how hundreds of possible mutations in a key cancer gene influence tumour growth.

Read more about a new map showing how hundreds of possible mutations in a key cancer gene influence tumour growth 👉 edin.ac/3NTaToX @andrewwood.bsky.social @roslininstitute.bsky.social @unileiden.bsky.social @koc-university.bsky.social @cmvm-edinburghuni.bsky.social

To cut a long story short: - Structure/Function analysis helps to understand why some CTNNB1 mutations disrupt degron function while others do not. - Common driver mutations show diverse levels of Wnt pathway activation.

- Cancers originating in different human tissues favour CTNNB1 mutations occupying distinct ranges of activation. - Hepatocellular carcinoma (HCC) patients with CTNNB1 mutations can be stratified into groups with low or high Wnt pathway activation

MRC National Mouse Genetics Network

This is the product of a long-running collaboration between my lab @uoe-igc.bsky.social, and Peter Hohenstein’s group @roslininstitute.bsky.social @unileiden.bsky.social, with wet-lab work led by Anagha Krishna and Derya Ozdemir, dry-lab work led by Alison Meynert and Martijn Kelder.

Andrew Wood reposted

@mrcmousenetwork.bsky.social

30 Jan

Our Best Models Working Group can offer advice on the use of a range of model systems. The next in our series highlighting our diverse expertise features Dr Andrew Wood, whose lab uses genome editing and targeted protein degradation to study genetic disease using cell lines, organoids, and mice.

nature.comCell-type-specific functionality encoded within the intrinsically disordered regions of OCT4 - Nature CommunicationsHere they perform a systematic dissection of OCT4 and reveal how intrinsically disordered regions can be used to serve specific functions during reprogramming and embryonic development. This can be exploited to engineer more efficient and specific reprogramming factors.

3 Oct 2025

With storm Amy approaching, it’s an ideal time to get your SLiPERs on!

Sally Lowell@cellysally.bsky.social

Hot off the press! Cell-type-specific functionality encoded within the intrinsically disordered regions of OCT4 www.nature.com/articles/s41...

Andrew Wood reposted

MRC National Mouse Genetics Network

@mrcmousenetwork.bsky.social

16 Sept 2025

On 14th November, we are once again holding our Network Science Day in York, which is an exciting opportunity for Network members and non-members to engage and develop new collaborations! The meeting is free to attend. Find out more and register by emailing us at Genetics_Network@har.mrc.ac.uk.

Andrew Wood reposted

Craig Kaplan

@triggerloop.bsky.social

3 Sept 2025

Look at this crazy thing! www.nature.com/articles/s41...

nature.comOne mother for two species via obligate cross-species cloning in ants - NatureIn a case of obligate cross-species cloning, female ants of Messor ibericus need to clone males of Messor structor to obtain sperm for producing the worker caste, resulting in males from the same moth...

journals.plos.orgTissue-specific consequences of tag fusions on protein expression in transgenic miceAuthor summary To better understand the function of specific proteins, researchers need ways to quantify their abundance, to visualise their movements, to understand what other molecules they interact...

26 Aug 2025

Our manuscript characterising tissue-specific consequences of tagged protein fusions in CRISPR-engineered mice is now online @PLOSGenetics. journals.plos.org/plosgenetics.... Thanks again to all coauthors, reviewers and editors for a smooth publication process. Brief summary below.

Andrew Wood@andrewwood.bsky.social

Pleased to share our latest work and the first manuscript from the Degron Tagging Cluster in the MRC National Mouse Genetics Network. If you work with protein tags, particularly in tissue biology models, this should be of interest: www.biorxiv.org/content/10.1...

nmgn.mrc.ukri.orgUnderstanding the Protein Tagging Problem: A New Study from the NMGN Degron Tagging Cluster | National Mouse Genetics NetworkCelebrating Research Specialists: Driving Innovation in Mouse Genetics Research specialists are often the unsung heroes in biomedical research groups, providing continuity in long-term research progra...

26 Aug 2025

Nice write up on the @mrcmousenetwork.bsky.social website, highlighting the awesome work of first author Gillian Taylor, is available here: nmgn.mrc.ukri.org/news/underst...

Andrew Wood reposted

Stephanie Borgland

@borglandlab.bsky.social

15 July 2025

www.genengnews.com/topics/trans...

genengnews.comWhy We Still Need Animal Research in a World of AI and OrganoidsThe portrayal of uncaring scientists without any thought for the animals being used in their research is far from the truth.

Andrew Wood reposted

Bruce Hamilton

@bahome.bsky.social

23 June 2025

Oliver Smithies was born 100 years ago today. Best known for gene targeting in mice, for which he shared the 2007 Nobel, he also developed starch gel electrophoresis in the 1950s. I met him once and remember him being very gracious and thoughtful. #genetics #OTD www.nobelprize.org/prizes/medic...

nobelprize.orgOliver Smithies – Facts - NobelPrize.orgOpen the search menuClose the search menuOpen the search menuClose the search menuSubmit a search termBack To Top

We characterise two underlying mechanisms with opposing effects on protein stability and explain their tissue-specificity, providing a rational basis for improved experimental design. Congrats to 1st author Gillian Taylor and all who contributed. Feedback welcome!

@cilialab.bsky.social @wpokrzywa.bsky.social @lumirare.com @cribdealmeida.bsky.social

Genetic tagging is a cornerstone of modern molecular biology, but it’s no secret that tag fusion often causes unwanted changes in protein expression and function. Understanding how this happens could help us to design more refined and effective models for preclinical research.