#elife

Camelids Against Coronavirus

Camelids – the camel family – are fascinating, not just because some have humps but because of their antibodies which are about half the size of human antibodies. Scientists have chopped up these little antibodies further to make tiny ‘nanobodies’ which are as effective at binding to proteins as their full-sized equivalent. Here, investigators identified a subset of nanobodies that bind the coronavirus spike protein. In the image, each blue disc is a cell culture and the grey splodges are where the coronavirus has entered, and killed, the cells. The top left culture has no nanobodies and in each subsequent disc the concentration of nanobody increases. At the bottom right there is almost no grey meaning that the nanobody concentration was sufficient to effectively neutralise the virus. Nanobodies are robust and can be cultured in large quantities cheaply making them an exciting prospect for Covid-19 therapy.

Written by Julie Webb

Image from work by Gang Ye, Joseph Gallant, Jian Zheng, and colleagues

Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN, USA

image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, August 2021

Lightness of Being

These colourful structures (fluorescently tagged) are the precursors of the light-sensitive nerve cells found at the back of the eye, called the retina. Light coming into the eye hits these cells, triggering nerve impulses that go to the brain where they’re interpreted to build a picture of the world around us. These particular cells are in the eye of a developing zebrafish embryo, which researchers are using as a stand-in for humans to understand more about how these cells divide and specialise during the earliest stages of life. Each of these nerve cells divides unequally, creating different ‘daughters’. This process builds up layers of cells in the retina with distinct properties, which is essential for it to function properly. Researchers have discovered that a gene called Notch plays an important role in controlling these unequal divisions, although in a different way than previously thought, revealing new insights into how eyes are made.

Written by Kat Arney

Image from work by Elisa Nerli, Mauricio Rocha-Martins and Caren Norden

Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany and Instituto Gulbenkian de Ciência, Oeiras, Portugal

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, November 2020

Reining-in Cancer

The sun bombards our skin with UV radiation, causing pro-cancer mutations to accumulate in the DNA of our skin cells. However, adult human skin cells are surprisingly tolerant of potent carcinogenic mutations without visible consequences. Research has shown that although these clusters of mutated cells persist, they remain limited in size. Researchers investigate why in mouse skin by introducing a pro-cancer mutation in the HRAS gene. Although some mutant cells divided to expand their numbers, acting as progenitor cells, others matured and were unable to proliferate. Looking more closely at the other genes involved, they focused on Rassf5, which is activated by HRAS. Among cells where Rassf5 protein levels were reduced (pictured in green in two slices of skin), progenitor cell numbers increased and the number of maturing cells reduced. Rassf5 is therefore vital in reining in the expansion of potentially dangerous mutated skin cells.

Written by Lux Fatimathas

Image from work by Madeline Sandoval, Zhe Ying and Slobodan Beronja

Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

Image originally published under a Creative Commons Licence (BY 4.0)

Published in eLife, January 2021

Disrupted Delivery

Inside each cell, a fleet of delivery vehicles ferry packages from A to B, ensuring proteins and nutrients are efficiently deposited where they are needed most. Any malfunction of these transporters, called endosomes, can cause traffic jams and protein pileups. WASHC4 (green in the mouse brain section pictured) is a protein involved in endosome trafficking, and previous research has shown that children with a genetic mutation affecting this protein have trouble learning. To investigate, researchers replicated this mutation in mice. The mice developed fewer WASHC4 proteins, oversized endosomes, and an excess of proteins that break down material, causing a build up of debris. The mice with this disrupted delivery system showed learning difficulties and developed movement problems that worsened with age, also found in patients with the mutation. Understanding the molecular basis for the physical symptoms could lead to new approaches to treatment or, even better, prevention.

Written by Anthony Lewis

Image from work by Jamie L Courtland and Tyler WA Bradshaw, and colleagues

Duke University School of Medicine, Durham, NC, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, March 2021

On the Clock

Insects like beetles have a body made up of different segments. Although you may not realise, human bodies – and those of other mammals – are also segmented, although in a less obvious way. During development in the womb, our spinal column is built from repeated segments known as somites, which are laid down in strict order from top to bottom. Using mouse embryos as a model for humans, researchers have been exploring how this clockwork somite pattern is created. The image on the left is a normal mouse embryo around 8 days after fertilisation. The activity levels of a gene called Hes7 highlighted in different colours from blue (low) through green and yellow (medium) to red (high), with the resulting stripes determining where the somites will grow. The embryo on the right has an alteration in a gene called Fgf4, disrupting the developmental clock and causing serious defects within the body.

Written by Kat Arney

Image from work by Matthew J Anderson and colleagues

Genetics of Vertebrate Development Section, Cancer and Developmental Biology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, MD,USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, November 2020

Flaming Brains

Every day, tiny immune cells called microglia and macrophages are hard at work in your brain keeping everything neat and tidy. They’re responsible for cleaning up biological waste, removing dead or unwanted cells and getting rid of invading bacteria and viruses. Because these cells are very similar, yet have slightly different specific roles, it’s hard to tease out exactly what each cell type is up to as the brain develops in the womb or during situations where there is a lot of immune activity (inflammation) such as injury or infection. In search of clarity, researchers have created genetically engineered mice carrying markers that make it easy to distinguish microglia from macrophages. These images show how the technique can be used to highlight macrophages using two different markers (rows) in three different parts of the brain (columns), enabling researchers to spy on what these cells are doing during development or inflammation.

Written by Kat Arney

Image from work by Gabriel L McKinsey and colleagues

Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, June 2020

Tiny Tubes

Inside every cell of your body there’s a complex biological ‘scaffold’ made of tiny tubes, known as the cytoskeleton. These tubes are made up of billions of actin molecules, which come together in a similar way that Lego bricks click together to make large, stable structures. However, actin doesn’t act alone. Other molecules help the actin tubes to assemble, giving them different structural properties depending on the job they need to do inside the cell. One of these, called vinculin, plays a particularly important role in building strong yet flexible actin bundles at the sites where cells join together. Researchers have been growing actin tubes in the lab, altering the proportions of actin (top row) and vinculin (bottom row) in the mixture to see what happens to the resulting structures. Their findings help to explain how cells reorganise their internal scaffolding to stick to each other and build a body.

Written by Kat Arney

Image from work by Rajaa Boujemaa-Paterski and colleagues

Department of Biochemistry, University of Zurich, Zurich, Switzerland

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, November 2020

Fishing for Teeth

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Life on Earth is the result of millions of years of fine-tuning – an evolution which often hides details of how things gradually became the way they are in extinct species, for curious scientists to discover. Here they use high-resolution x-ray microtomography to picture the jawbone of a fossilised bony fish Lophosteus, revealing its 422-million-year-old teeth (highlighted in gold) and virtually 'removing'the bone to peek at the blood vessels and pulp cavities (blue and green) underneath. This fish was picked for a reason – it’s an early window into the evolution of teeth, showing that structures called dermal odontodes (purple pink and red) developed from similar cells to teeth, becoming nearby 'skin teeth' – the scales in fish like sharks. The co-development of these structures reveals more about the chemical signals driving how teeth develop and grow, and may provide insights into the signals shaping human gnashers too.

Written by John Ankers

Image from work by Donglei Chen and colleagues

Department of Organismal Biology, Uppsala University, Uppsala, Sweden

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, December 2020