Illustration of a diverse primary tumour whose genome has been sequenced.

Research highlights July - September 2019

In our research highlights series, representatives of our faculty select their most significant publications from the Crick each quarter. This time, the picks include cancer superhighways, t-loops and a new step towards understanding motor neurone disease.

Boulton lab

Unravelling the protective properties of t-loops

CDK phosphorylation of TRF2 controls t-loop dynamics during the cell cycle

Sarek et al., Nature, 575, 523-527 (2019)

The winding and unwinding of ‘t-loops’ at the end of telomeres protects chromosomes from being recognised as DNA damage, finds research led by Simon Boulton's group. The study also uncovered how this process is regulated.

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Goehring lab

How size affects a cell's fate

A cell-size threshold limits cell polarity and asymmetric division potential

Hubatsch et al., Nature Physics, 15, 1078-1085 (2019)

A new study from Nate Goehring's group investigates how cell polarity networks respond to changes in cell size. Their work suggests that cells may be able to read out their size in order to decide whether to divide symmetrically or asymmetrically, all based on a Turing-like reaction-diffusion system.

Kassiotis lab.

A ‘jumping gene’ creates an immune checkpoint

Soluble PD-L1 generated by endogenous retroelement exaptation is a receptor antagonist

Ng et al., eLife, 8, e50256 (2019)

A new study led by George Kassiotis's group investigates endogenous retroelements (EREs), which provide genetic diversity for our evolution. They found that one particular ERE has generated a form of the immune checkpoint PD-L1 with countering activity.

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Malanchi lab.

Cancer cells ‘corrupt’ their healthy neighbours

Metastatic-niche labelling reveals parenchymal cells with stem features

Ombrato et al., Nature, 572, 603-608 (2019)

A new study, which uses a state-of-the-art technique developed by Ilaria Malanchi's group, has found that the healthy cells immediately surrounding a tumour become more stem cell-like and support cancer growth.

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Patani & Luscombe labs.

New molecular link discovered in motor neurone disease

Widespread FUS mislocalization is a molecular hallmark of amyotrophic lateral sclerosis

Tyzack et al., Brain, 142, 2572-2580 (2019)

A study led by Rickie Patani and Nick Luscombe has found that a protein implicated in a minority of motor neurone disease (MND) cases - the FUS protein - is likely to contribute to pathology of the disease in all patients.

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Ralser lab.

Uncovering an antioxidant mechanism

Lysine harvesting is an antioxidant strategy and triggers underground polyamine metabolism

Olin-Sandoval et al., Nature, 572, 249-253 (2019)

A new study from Markus Ralser's group describes a powerful but overlooked antioxidant mechanism, known as lysine harvesting – a metabolic adaption that protects microbial cells in stress situations.

Ratcliffe lab.

Oxygen sensing across kingdoms

Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants

Masson et al., Science, 365, 65-69 (2019)

Research led by Peter Ratcliffe has discovered an enzymatic oxygen sensor in humans that is functionally identical to plant cysteine oxidases, enzymes that control responses to hypoxia in plants. Further study of this enzyme in humans could lead to new therapeutics targeting diseases related to impaired oxygen sensing.

Sahai and Bates lab

New insights could help block the path of cancer ‘super-highways’

Extracellular matrix anisotropy is determined by TFAP2C-dependent regulation of cell collisions

Park et al., Nature Materials (2019)

Matrix feedback enables diverse higher-order patterning of the extracellular matrix

Wershof et al., PLOS Computational Biology, 15, e1007251 (2019)

A key mechanism controlling tissue structure, which could help identify drugs that make it harder for cancer cells to spread, has been identified by two new studies led by Paul Bates and Erik Sahai's groups at the Crick.

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Swanton lab

New genetic test could predict cancer survival

A clonal expression biomarker associates with lung cancer mortality

Biswas et al., Nature Medicine, 25, 1540-1548 (2019)

A new genetic test to distinguish between high- and low-risk tumours, which could help doctors and patients to make crucial treatment decisions, has been developed by a London-led international consortium including the Charlie Swanton's group at the Crick, the Bioinformatics and Biostatistics team and the Genomics Equipment Park.

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Treeck lab.

Unlocking the genetic secrets of the malaria parasite

A novel tool for the generation of conditional knockouts to study gene function across the Plasmodium falciparum life cycle

Tibúrcio et al., mBio, 10, e01170-19

A study led by Moritz Treeck's group provides a new way for researchers to delete genes from the malaria parasite at late stages in its life cycle. This new method paves the way for developing a greater understanding of the disease, which could lead to new vaccines and treatments.

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