Research highlights

IMAGE: EMBL/Mayya Sundukovna, Laura Batti & Giulia Bolasco

print

The first edition of our new quarterly summary of some recent research papers from across EMBL

Cells

In organoid cultures, mouse residual breast cancer cells have elevated lipid metabolism (green). CREDIT: Jechlinger/EMBL

In organoid cultures, mouse residual breast cancer cells have elevated lipid metabolism (green). IMAGE: Jechlinger/EMBL

How chromosomes form
In collaboration with scientists at Columbia University and TU Delft, the Haering group have revealed a possible mechanism by which a protein complex called condensin packs DNA into chromosomes. The study has shown that condensin acts like a molecular motor, moving with much larger steps than any other known motor protein.
Terakawa et al., Science, doi: 10.1126/science.aan6516

Condensin safety belt
The Haering group have published a study that reveals how the condensin complex interacts with DNA. Part of the complex encircles the DNA molecule and acts like a safety belt to hold the DNA in place. This novel way of DNA binding provides key insights into the molecular mechanism of condensin-mediated chromosome organisation.
Kschonsak et al., Cell, doi: 10.1016/j.cell.2017.09.008

Cell changes drive breast cancer relapse
Researchers in the Jechlinger group have identified features of residual breast cancer cells that suggest new approaches for preventing relapse.
Havas et al., J Clin Invest, doi: 10.1172/JCI89914

Shaping contraction waves in egg cells
The Lenart group have identified molecular activities that drive shape changes in oocytes crucial in the coordination of cell division and the subsequent development of an embryo. The team has shown how spatial gradients formed by these activities pattern surface contraction waves – shape changes typical to all animal egg cells.
Bischof et al., Nat Commun, doi: 10.1038/s41467-017-00979-6

Predicting the behaviour of the cytoskeleton
The Leptin and Nédélec groups have developed a theoretical framework to predict whether a network of protein filaments – like that which makes up the cytoskeleton, giving a cell its shape – will contract, expand, or retain its size. This provides a foundation for studying a broad range of processes involving cytoskeletal networks.
Belmonte et al., Mol Syst Biol, doi: 10.15252/msb.20177796

New insights into blood cell mechanics
The Nédélec group have published work detailing how, in red blood cells, a delicate balance between a peripheral ring of microtubules and the tension in the cell’s cortical actin layer impacts the cell’s overall size and shape.
Dmitrieff et al., Proc Natl Acad Sci USA, doi: 10.1073/pnas.1618041114

How wine-making yeast can feed wine-spoiling bacteria
A study by scientists in the Patil group details how the microbes involved in making wine, yoghurt and other fermented foods can feed each other. The work also shows that a small change in the environment can shift the interaction from a one-way relationship into a mutual dependency.
Ponomarova et al., Cell Syst, doi: 10.1016/j.cels.2017.09.002

HipSci: The human stem cell bank
Stem-cell researchers have produced one of the largest collections of high-quality human induced pluripotent stem cell lines (iPSCs) from healthy individuals. This resource is a result of a close collaboration between the Stegle group and their partners in a major international collaboration. The datasets are freely available via EMBL-EBI.
Kilpinen et al., Nature, doi:10.1038/nature22403

Development

Combined images from light microscopy and electron microscopy reveal what a speck formed in vivo (in blue) looks like. IMAGE: EMBL/Schwab Team

Combined images from light microscopy and electron microscopy reveal what a speck formed in vivo (in blue) looks like in a study published by Kuri et al. IMAGE: EMBL/Schwab Team

Mapping gene expression cell by cell
The Arendt group have completed a molecular atlas showing gene expression in all cells in a whole organism, studying the expression patterns of more than 100 important genes in each cell of the marine worm Platynereis dumerilii.
Vergara et al., Proc Natl Acad Sci USA, doi: 10.1073/pnas.1610602114

Newly found regulator of important developmental protein
Scientists in the Ephrussi and Müller groups have discovered that some important proteins, including one known as Oskar, contain a specific variant of the LOTUS domain that regulates Vasa, a conserved protein involved in development of the germline in animals. The team have discovered how the proteins interact, by determining the structure of the Oskar LOTUS domain bound to Vasa.
Jeske et al., Genes Dev, doi: 10.1101/gad.297051.117

The dynamics of inflammatory response
Researchers in the Leptin group have explored the dynamics of the formation of ASC specks, protein clusters that are responsible for a key step in triggering the cell’s inflammatory response. The process has been visualised in vivo in zebrafish.
Kuri et al., J Cell Biol, doi: 10.1083/jcb.201703103

Genomes 

Mouse disease models

The International Mouse Phenotyping Consortium published hundreds of new mouse disease models and reveals previously unknown gene functions in a study published by Meehan et al. IMAGE: Spencer Phillips, EMBL-EBI

Bowel cancer study reveals impact of mutations on protein networks
Scientists used a computational analysis method developed by EMBL-EBI researchers and their colleagues to explore how common mutations affect proteins in bowel cancer cells, and whether identifying these proteins can help predict the cancer’s response to treatment.
Roumeliotis et al., Cell Rep, doi: 10.1016/j.celrep.2017.08.010

Novel hearing loss genes identified
Researchers from the Flicek and Parkinson groups and their collaborators have found 52 previously unidentified genes that are critical for hearing. The study shows how these newly discovered genes could provide insights into the causes of hearing loss in humans.
Bowl et al., Nat Commun, doi: 10.1038/s41467-017-00595-4

Using distant relatives to understand the effects of sequence variation
The Furlong group have studied the occupancy of key regulatory factors in two distinct strains of Drosophila to better understand the effects of natural sequence variation. The paper analyses the relationship between DNA sequence and function during evolution.
Khoueiry et al., Elife, doi: 10.7554/eLife.28440

Mouse genes could help decipher human disease
Researchers in the Parkinson group and their collaborators have fully characterised thousands of mouse genes for the first time. The results offer hundreds of new disease models and reveal previously unknown gene functions.
Meehan et al., Nat Genet, doi: 10.1038/ng.3901

Structures

 Exit route for virulence factors involved in tuberculosis. IMAGE: Tobias Wüstefeld

Exit route for virulence factors involved in tuberculosis. IMAGE: Tobias Wüstefeld

Automated identification of crystallographic ligands
Scientists in the Lamzin group have presented a new approach for the automated identification of crystallographic ligands, developed along the themes of the world-leading ARP/wARP software. The method is based on the estimation of different energy terms involved in protein–ligand interaction and will help increase the reliability of protein-ligand models in the Protein Data Bank.
Beshnova et al., Acta Crystallogr, doi: 10.1107/S2059798317003400

New validation tool for protein backbone geometry
Researchers in the Lamzin group have unveiled DipCheck, a new method that uses a novel 3D parameter space to validate the geometry of the backbones that build up the hugely diverse conformations of the structures of proteins. DipCheck is now available to researchers across the globe through a new web service. The Lamzin group has used the tool to detect geometrically strained structural regions that have an impact on the function of proteins.
Pereira & Lamzin., IUCrJ, doi: 10.1107/S2052252517008466

A new version of ATSAS to elucidate macromolecular structures in solution
The Svergun group presented numerous recent improvements and new developments to ATSAS, a program suite for small-angle scattering data analysis from macromolecular solutions. The software has over 13,000 users worldwide.
Franke et al., J Appl Crystallogr, doi: 10.1107/S1600576717007786

Reconciliation of discrepancies between SAXS and FRET results
The Svergun and Lemke groups have collaborated to publish a paper reconciling a long-standing controversy between small-angle X-ray scattering (SAXS) and Förster Resonance Energy Transfer (FRET) results in measurements of intrinsically disordered proteins.
Fuertes et al., Proc Natl Acad Sci USA, doi: 10.1073/pnas.1704692114

Uncovering the biology of tuberculosis
The Wilmanns group have revealed the molecular structure of important bacterial secretion systems – essential for the full growth and virulence of Mycobacterium tuberculosis.
Beckham et al., Nat Microbiol, doi: 10.1038/nmicrobiol.2017.47

Detailing the structure of a key multi-protein co-activator
Using EMBL’s macromolecular crystallography beamline P14 at the PETRA III synchrotron radiation source in Hamburg, a group of researchers led by Patrick Cramer of the Max Planck Institute for Biophysical Chemistry, have determined the crystal structure of the Core Mediator, a key regulator of RNA polymerase, at unprecedented resolution.
Nozawa et al., Nature, doi: 10.1038/nature22328

Models

Artist's representation of the sexual dimorphism dilemma. IMAGE: Spencer Phillips, EMBL-EBI

Artist’s representation of the sexual dimorphism dilemma. IMAGE: Spencer Phillips, EMBL-EBI

Revealing a sexual dimorphism dilemma
Scientists in the Parkinson group and their collaborators have quantified differences between 50,000 male and female mice, showing that gender is a very important consideration when designing studies.
Karp et al., Nat Commun, doi: 10.1038/ncomms15475