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Alternative DNA repair pathway for MDC1

Salguero and colleagues in the Jackson lab have found an alternative pathway to elicit the DNA-damage response that does not depend on the protein H2AX. They show that MDC1, which was previously believed to work only when interacting with phosphorylated H2AX, in fact retains its capacity to recruit repair factors to the site of DNA damage even when H2AX is absent. This may enable DNA repair in areas of the genome known to be depleted of H2AX.

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Inhibiting the Fanconi anemia pathway

Galanty and colleagues in the Jackson lab identify two small-molecule inhibitors of the Fanconi anemia pathway, necessary for cancer cells that are - or become - resistant to DNA cross-linking therapeutics. These provide leads for development of drugs to re-sensitise tumours to cross-linking agents such as cisplatin.

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Don't get your DNA in twist

New paper by the Zegerman lab shows that limiting the rate of DNA duplication - by limiting the number of DNA replication initiation events - is important to prevent intertwining between the newly replicated chromosomes. This work may be relevant for the treatment of cancer cells, which are characterised by high rates of DNA duplication.

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How to boost adult liver regeneration

A new paper in Nature Cell Biology from the Huch lab - with collaborators in the Gurdon Institute, UK and Germany - describes the molecular mechanism triggered by TET1 that allows damaged adult liver cells to regenerate. This paves the way for design of drugs to boost regeneration in conditions such as cirrhosis or other chronic liver diseases where regeneration is impaired.

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Mitochondrial metabolism important for stem cell diversity

Research from the Brand lab shows that blocking the energy supply from mitochondria reduces brain tumour growth and limits cell diversity. This is relevant for anti-cancer therapies aimed at blocking mitochondrial metabolism, because they may have wider effects on cancer cell behaviour than just preventing tumour cell proliferation.

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New DNA stability genes uncovered in systematic study of Yeast Knockout Collection

The Jackson lab applied next-generation DNA sequencing to over 4500 yeast strains in the Gene Knockout Collection. The resulting comprehensive resource identifies new genes responsible for maintaining the stability of DNA in cells, and whose absence or mutation leads to a variety of effects, from changes in short sequence repeats to the loss of whole chromosomes. These 'mutational signatures' can now also be studied in human cells.

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Spinouts from the Gurdon

Our final video in the series 'A Year in Institute Life' looks at two current examples of the many spinout companies and enterprises to come from the Gurdon Institute. In the clip shown, Kathryn Chapman, Deputy Director of the Milner Therapeutics Institute, describes their mission and shows us their new premises.

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Next Gurdon Institute Seminar

On Tuesday 26th November at 11.30am we will hear from Lori Passmore, from MRC Laboratory of Molecular Biology, Cambridge, on 'Mechanistic insights into the mRNA poly(A) tail machinery and DNA repair'. All welcome.

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We're hiring

Several great opportunities to join the Gurdon Institute are on offer right now, from Group Leader in the area of radiation biology in cancer to a PhD studentship with our newest GL.

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Steve Jackson awarded ERC Synergy Grant

Recipients of the ERC Synergy Grants have just been announced and Steve Jackson at the Wellcome Trust/ Cancer Research UK Gurdon Institute is among them, awarded funding for a project on the DNA damage response in collaboration with partners in Switzerland and Austria. This is the first of the new Horizon 2020 grants to come to Cambridge.

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An artist's view of the Rawlins lab

Artist Caroline Walker was commissioned by Cambridge University Library to capture images of women working in the lab at the Gurdon Institute. After shadowing researchers in the Rawlins lab and taking photographs, Caroline created this large oil painting now on view at the UL's exhibition, 'The Rising Tide: Women at Cambridge'.

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We are recruiting GLx1

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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MDC1 PST-repeat region promotes histone H2AX-independent chromatin association and DNA damage tolerance

Checkpoint inhibition of origin firing prevents DNA topological stress

Small Molecule Inhibition of UBE2T/FANCL-mediated Ubiquitylation in the Fanconi Anemia Pathway

Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration

Neurogenin3 phosphorylation controls reprogramming efficiency of pancreatic ductal organoids into endocrine cells

Mutations in thyroid hormone receptor α1 cause premature neurogenesis and progenitor cell depletion in human cortical development

Neural stem cell temporal patterning and brain tumour growth rely on oxidative phosphorylation

Testing the role of SOX15 in human primordial germ cell fate

Genome architecture and stability in the Saccharomyces cerevisiae knockout collection

Long noncoding RNAs are involved in multiple immunological pathways in response to vaccination

Defining the Identity and Dynamics of Adult Gastric Isthmus Stem Cells

Interaction of Sox2 with RNA binding proteins in mouse embryonic stem cells

Disease modelling in human organoids

The role of integrins in Drosophila egg chamber morphogenesis

Tracing the cellular dynamics of sebaceous gland development in normal and perturbed states

Neural stem cell dynamics: the development of brain tumours

Liver organoids: from basic research to therapeutic applications

NSUN2 introduces 5-methylcytosines in mammalian mitochondrial tRNAs

 

Link to full list on PubMed