Research highlights October - December 2019

In our research highlights series, representatives of our faculty select their most significant publications from the Crick each quarter.

Briscoe lab

The influence of neuronal differentiation 

Neuronal differentiation influences progenitor arrangement in the vertebrate neuroepithelium

Guerrero et al., Development, 146, decv176297 (2019)

A study from James Briscoe has used simulations of the developing neural tube that model the cellular mechanics and dynamics to provide insight into how proliferation and differentiation affect tissue growth.

Cherepanov lab

How HIV develops drug resistance

Structural basis of second-generation HIV integrase inhibitor action and viral resistance

Cook et al., Nature, 367, 806-810 (2020)

The mechanism behind how HIV develops resistance to a widely-prescribed group of drugs has been uncovered by new research from the Crick and Dana-Farber Cancer Institute, with the findings opening the door to the development of more effective treatments.

Read the full news story.

Costa lab.

Cryo-EM explains how cells prepare for DNA replication

Mechanism of head-to-head MCM double-hexamer formation revealed by cryo-EM

Miller et al. Nature, 575, 704-710 (2019)

A team from Alessandro Costa's group, with John Diffley, used high-resolution 3D cryo-electron microscopy to observe the cascade of molecular events that prepare the DNA double helix for replication.

Hayday lab.

3i Project - a genetic resource for immunology

High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation

Abeler-Dörner et al., Nature Immunology21, 26-100 (2020)

A large collaborative project, led by Adrian Hayday, has developed an immunophenotyping platform with high-throughput genetic screening. This community resource provides an improved understanding of immune variation in health and disease, and proposed better ways to monitor it. It also identified scores of immunoregulatory genes that were never previously implicated in immunology.

Li lab.

Two genes slow down the development of intestinal tumours

NEDD4 and NEDD4L regulate Wnt signalling and intestinal stem cell priming by degrading LGR5 receptor

Novellasdemunt et al., The EMBO Journal, 39, e102771 (2020)

Benign intestinal tumours with mutations that delete or inactivate two particular tumour-suppressing genes develop more quickly towards cancerous forms, according to new research from Vivian Li's group.

Read the full news story.

Oliferenko lab

Comparing the membrane lipidome

Delineating the rules for structural adaptation of membrane-associated proteins to evolutionary changes in membrane lipidome

Makarova et al., Current Biology, 30, 367-380.e8

New research from Snezhka Oliferenko's group has found that different membrane lipid compositions in two sister yeast species may be at the root of remarkable differences in fundamental membrane-centered processes. 

Ralser lab

New software suite accelerates proteomics: DIA-NN

DIA-NN: neural networks and interference correction enable deep proteome coverage in high throughput

Demichev et al., Nature Methods, 17, 41-44 (2020)

A paper from Markus Ralser's group describes a new, easy-to-use suite of software algorithms they have developed, which exploits deep neural networks for faster and more precise proteomic experiments.

Rittinger lab

New insights into ubiquitin transfer inhibitors 

Single-domain antibodies as crystallization chaperones to enable structure-based inhibitor development for RBR E3 ubiquitin ligases

Tsai et al., Cell Chemical Biology, 27, 83-93.e9 (2020)

Research from Katrin Rittinger's lab in collaboration with GlaxoSmithKline, identifies new tools that provide insight into the mechanism of ubiquitin transfer by an E3 ligase and facilitate its crystallization and thus helps to develop structure-based inhibitors.

Tolar lab

How immune cells extract antigens

B cells extract antigens at Arp2/3-generated actin foci interspersed with linear filaments

Roper et al., eLife, 48093 (2019)

A paper from Pavel Tolar's lab with Michael Way has used super-resolution microscopy to study the mechanics behind how the cytoskeleton supports B cells forming immune synapses to extract antigens.

Vousden lab

Tumour-associated loss of p53

Cancer-specific loss of p53 leads to a modulation of myeloid and T cell responses

Blaigh et al., Cell Reports, 30, 481-496.e6 (2020)

Research led by Karen Vousden's group has shown that cancer-specific loss of p53, a tumour suppressor, promotes immune tolerance through the recruitment of myeloid and Treg populations within the tumour microenvironment.