Articles of the Month 2022
Archive of previous entries
Some of the most severe insect pests are invasive species such as Drosophila suzukii. Their invasive success is achieved in part due to their extremely robust immune system, which makes them difficult to control. In December's article of the month, Carrau et al. investigate the innate immunity of D. suzukii and reveal some of the underlying mechanisms. In the human immune system, one of the first lines of defense against invading bacteria is the activation of neutrophils, which catch bacteria in so-called neutrophil extracellular traps (NETs) formed from the cells' own DNA as they die. Carrau et al. found that the equivalent immune cells in D. suzukii (plasmatocytes) also produce extracellular traps, in addition to deploying other strategies such as engulfing the invading bacteria (phagocytosis) and trapping them on cellular extensions (filopodia). The more we learn about the defense mechanisms of insect pests, the easier it becomes to develop strategies that overcome or circumvent those mechanisms as a means of pest control.
Article details: Carrau T et al. (2021) The cellular innate immune response of the invasive pest insect Drosophila suzukii against Pseudomonas entomophila involves the release of extracellular traps. Cells 10 (12) 3320.
Image shows a neutrophil (yellow) that has ejected a NET (green) to capture bacteria (purple), with the collateral effect of also trapping a red blood cell (orange).
Image credit: CHDENK (CC BY-SA 4.0)
Insect pests cause immense damage to crops, but traditional control methods based on chemical pesticides are becoming less effective because insect populations are evolving resistance. One way to counter this is the release of volatile compounds (odorants) that direct insect behavior, including their ability to identify food, mates, and predators, but the underlying molecular mechanisms are often unclear. In November's article of the month, Chen et al. show how the volatile compound methyl eugenol is detected by the oriental fruit fly (Bactrocera dorsalis). They provide direct physical evidence that methyl eugenol binds to the receptor BdorOBP56f-2, and then confirm its biological role by knocking out the corresponding gene and showing that flies no longer respond to this chemical. Uncovering the molecular basis of odorant perception in pest insects will facilitate the development of new control strategies to protect crops.
Article details: Chen X et al. (2021) CRISPR/Cas9 mutagenesis abolishes odorant-binding protein BdorOBP56f-2 and impairs the perception of methyl eugenol in Bactrocera dorsalis (Hendel). Insect Biochem Mol Biol 139, 103656.
Image shows a female oriental fruit fly (Bactrocera dorsalis) laying eggs under the skin of a papaya fruit.
Image credit: Scott Bauer/USDA (public domain).
Ancient DNA can provide fascinating insights into the lives of historical figures to fill gaps in written archives or support findings based on other contemporaneous sources. As DNA sequencing technology becomes more powerful, so it becomes possible to find information even when the source material is hundreds or even thousands of years old. In October's article of the month, Iadarola et al. apply a technique known as exome sequencing to home in on the coding regions of DNA extracted from the mummified remains of Cangrande della Scala. This Italian nobleman (1291–1321) was the ruler of Verona and surrounding cities until his death, and he was interred in a marble tomb that helped to preserve his body. The reconstructed DNA sequence suggests that Cangrande della Scala represents the earliest known case of the lysosomal storage disorder now known as Pompe disease, which fits well with historical accounts of his poor health. Even small amounts of preserved tissue are sufficient for this approach, which could therefore provide new information about genetic heritage to support historical research.
Article details: Iadarola B et al. (2021) Whole-exome sequencing of the mummified remains of Cangrande della Scala (1291–1329 CE) indicates the first known case of late-onset Pompe disease. Sci Rep 11 (1) 21070.
Image shows an equestrian Statue of Cangrande della Scala at the Museo di Castelvecchio, Verona, Italy.
Image credit: this image in the public domain
Chicory is used as a salad leaf and also as an industrial source of the food additive inulin. However, the waste biomass left after inulin extraction is full of bioactive molecules that can be extracted to gain additional value. In September's article of the month, Häkkinen et al. show that chicory extracts prepared using a variety of solvents and techniques possess a remarkable range of biological activities, including the ability to suppress the growth of antibiotic-resistant bacteria and to prevent biofilm formation by the yeast Candida albicans. Plants such as chicory could therefore be used in the future as a source of natural antimicrobial compounds to address the shortage of new antibiotics in the development pipeline. Furthermore, the use of waste fractions from an existing industrial process provides a way to valorize plant material that is usually discarded or incinerated.
Article details: Häkkinen ST et al. (2021) Chicory extracts and sesquiterpene lactones show potent activity against bacterial and fungal pathogens. Pharmaceuticals 14 (9) 941.
Image shows a chicory flower.
Image credit: Jim/Code Poet (CC BY-NC-SA 2.0).
The production of recombinant proteins in plants rather than microbes or mammalian cells can be be advantageous in terms of speed, safety and scalability, but downstream processing and purification can be more challenging because the product is mixed with a large number of host cell proteins. In August's article of the month, Bernau et al. show how the mathematical modeling of chromatography can predict the most suitable conditions for protein purification, reducing the costs of process optimization. They identified the main sources of variation resulting from the selection of different chromatography settings, but also found that cultivation conditions such as the greenhouse temperature can have a profound impact on the behavior of host cell proteins and the corresponding chromatography binding parameters. The application of such models can help to improve the purification process for pharmaceutical proteins such as therapeutic antibodies.
Article details: Bernau CR et al. (2021) Precision analysis for the determination of steric mass action parameters using eight tobacco host cell proteins. J Chromatogr A 1652, 462379.
Image shows a space-filling model of the most abundant plant host cell protein, the enzyme RuBisCO.
Image credit: wwPDB, created with NGL Viewer.
The common clothes moth (Tineola bisselliella) is one of the few insect species that can digest keratin, the major protein component of wool and some other natural fabrics (as well as natural structures such as hair, nails and feathers). Although the adults do not feed, the larvae are notorious pests that destroy clothing and other textiles. In July's article of the month, Schwabe et al. provide insight into the mechanism of keratin digestion by comparing transcriptome datasets from larvae reared exclusively on keratin-rich diet of feathers and those raised on a keratin-free diet. The feather diet induced the expression of more than 30 enzymes, including collagenases and other proteases as well as enzymes that help to reduce disulfide bonds. The identification of specific enzymes that allow larvae to feed on keratin could facilitate the development of targeted control strategies based on enzyme inhibition.
Article details: Schwabe M et al. (2021) Next-generation sequencing analysis of the Tineola bisselliella larval gut transcriptome reveals candidate enzymes for keratin digestion. Genes 12 (8) 1113.
Image shows a clothes moth larva.
Image credit: Lamiot (CC BY-SA 3.0)
Biopharmaceutical proteins such as antibodies are typically produced in mammalian cells, including the human cell line HEK-293T. The yield of such proteins can be improved by cell line engineering, which aims to balance cell growth, viability and productivity. In June's article of the month, Kronenberg et al. show that a plant regulatory protein known as NtFT4, which controls flowering in response to day length in tobacco, can improve the proliferation of several human cell lines without compromising viability or productivity. The transfection of HEK-293T cells usually reduces the density of viable cells, but the expression of NtFT4 overcomes this hurdle and allows the dense cultivation of transfected cells and thereby increases the yield of a recombinant antibody by more than 30%. This engineering strategy could be combined with other forms of process optimization to boost the yield of recombinant proteins even further.
Article details: Kronenberg J et al. (2021) The tobacco phosphatidylethanolamine-binding protein NtFT4 simultaneously improves vitality, growth and protein yield in human cells. Biotechnol Bioeng 118 (10) 3770–3786.
Image shows fluorescence microscopy of HEK-293 cells loaded with the dye Flou-4.
Image credit: Borys Olifirov (CC BY 4.0)
The modification of staple cereals to increase nutrient levels in the seeds is a common approach to develop new varieties that prevent diseases of malnutrition. However, it is often unclear how such interventions affect the metabolism of the vegetative tissues of the same plants, particularly the leaves and roots. In May’s article of the month, Girón-Calva et al. carried out a comprehensive metabolic comparison of normal maize plants and a variety engineered to accumulate carotenoids in the seeds, focusing on the metabolic profiles of the leaves and roots. Not only did they find differences in vegetative metabolism between the two plant lines, but also different responses to high or low levels of nitrogen in the fertilizer. These different vegetative responses arose even before seed development and thus cannot be a direct response to metabolic engineering in the seed, suggesting that the differences are somehow already primed at the embryonic stage. This model of transgenerational metabolic priming could help to predict the outcome of metabolic engineering.
Article details: Girón-Calva PS et al. (2021) Nitrogen inputs influence vegetative metabolism in maize engineered with a seed-specific carotenoid pathway. Plant Cell Rep 40 (5) 899–911.
Image shows a collection of maize cobs.
Image credit: Parmveer Singh (CC BY-SA 3.0).
Plant viruses can be developed as vaccines by engineering them to display proteins or peptides from other viruses responsible for diseases in humans, including epitopes of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19. Although vaccines based on plant viruses are advantageous because they do not replicate in humans, they induce a strong immune response, and they are easy to produce in large quantities using plants, one drawback is they are rapidly broken down once injected, so multiple doses are required. In April's article of the month, Nkanga et al. show how plant viruses can be formulated as hydrogels that slowly dissolve and release the virus particles continuously, maintaining a strong immune response. Such injectable hydrogels offer a promising single-dose replacement for multiple doses of conventional vaccines.
Article details: Nkanga CI et al. (2022) Injectable slow-release hydrogel formulation of a plant virus-based COVID-19 vaccine candidate. Biomacromolecules 23 (4) 1812–1825.
Image shows a computer model of Cowpea mosaic virus, which was used to display the SARS-CoV-2 epitopes in this study.
Image credit: Thomas Splettstoesser (CC BY-SA 3.0)
Melt electrospinning is a manufacturing process in which fibres are formed from molten polymers. The liquid polymer is pushed through a nozzle into an electric field, which causes the formation of elongated jets. The cooling polymer fibres are then deposited onto a collector. The properties of the fibres depend on the temperature, take-up speed and various other parameters, and also on the presence of additives. In our article of the month for March, Siebert et al. tested two different additives as nucleation agents for their effect on fibre crystallinity and the corresponding mechanical properties. They found that the type and concentration of nucleating agents interacted with the spinning parameters to create a design space within which fibres of different mechanical characteristics could be produced. The simultaneous testing of different parameters will allow process improvements and optimization on a larger scale.
Article details: Siebert S et al. (2022) Nucleating agents to enhance poly(L-lactide) fiber crystallization during industrial-scale melt spinning. Polymers 14 (7) 1395.
Image shows melt-electrospun fibres.
Image credit: Daltster (CC BY-SA 3.0)
Aureolysin is an enzyme and virulence factor secreted by the bacterium Staphylococcus aureus. More precisely, it is a metalloprotease, an enzyme that breaks down proteins and requires one or more metal ions as part of the catalytic mechanism. The biological role of aureolysin is to break down proteins from the host immune system, helping the bacterium to evade the immune response. Drugs that specifically inhibit aureolysin would therefore be ideal for the treatment of S. aureus infections. In February's article of the month, Mendes et al. engineered an insect metalloprotease inhibitor (IMPI) to increase its efficacy against aureolysin. They solved the crystal structure of aureolysin-IMPI complexes to determine the precise mechanism of action, allowing the design of IMPI mutants to bind and cleave aureolysin more efficiently. One of the mutants achieved a better inhibition constant than wild-type IMPI and is therefore suitable as a lead for the development of drugs against antibiotic resistant S. aureus strains,
Article details: Mendes SR et al. (2022) An engineered protein-based submicromolar competitive inhibitor of the Staphylococcus aureus virulence factor aureolysin. Comp Struct Biotechnol J 20, 534–544.
Image shows S. aureus cells.
Image credit: NIAID (CC BY-SA 2.0).
Plants synthesize a diverse range of complex molecules known as secondary metabolites. These natural products can be exploited by humans as drugs, dyes, nutrients, flavors, perfumes and even poisons. In nature, secondary metabolites tend to be produced in very small quantities and many are toxic if they accumulate beyond a certain concentration. In January's article of the month, Buntru et al. show how cell-free expression systems based on plant cell lysates can overcome this barrier. Cell-free lysates are the internal contents of cells, but they are no longer alive and are therefore unaffected by toxins and inhibitors that kill plant cells or prevent them from growing and dividing. Lysates derived from tobacco cells were shown to produce four diverse metabolites when provided with the appropriate genetic constructs: lycopene (the red pigment from tomatoes, pictured), indigoidine (a blue pigment from bacteria) and two betalains (yellow/orange and red/violet pigments from plants such as beetroot). Cell lysates can now be developed to produce other metabolites, including valuable pharmaceutical structures.
Article details: Buntru M et al. (2022) Plant-derived cell-free biofactories for the production of secondary metabolites. Front Plant Sci 12, 794999.