Nucleotides Briefing 29/09/23
Read on to learn about advances in CAR-T cell therapy, climate impacts on French viticulture, jelly-fish learning, and virus directed evolution of biomolecules
Your Weekly Briefing
This week’s picture is a snap of a coral reef near Mayotte Island in the Indian Ocean. See Nature for the rest!
Dynamic fine-tuning of CAR-T cell therapy
CAR-T cells are T Lymphocytes (immune cells) that have been genetically modified to express CARs (chimeric antigen receptors) on their surface, allowing them to recognize tumour proteins. This has been used to treat acute lymphoblastic leukaemia and non-Hodgkin’s lymphoma. However, significant safety concerns remain due to the difficulty of controlling the activity of the engineered cells. This can lead to cytokine release syndrome (CRS), neurotoxicity, and organ damage. To achieve dynamic control of the cells, Lainšček et al. selected the nuclear factor of activated T cell 2 (NFAT) and attached it to a heterodimerization system (HDs are two proteins that can bind to each other in the presence of a small molecule). The corresponding protein partner was fused to a transcription activator or repressor domain. Thus, the addition of one of two different molecules can externally control an activator or a repressor which increase or down-tunes CAR-T cell activity, respectively. This may increase the safety and effectiveness of CAR-T cell treatment.
Changing old viticulture for all the right rieslings
Among the 1,298 French respondents of a 2019 survey, 80% said they are noticing the impacts of climate change on vine performance and wine quality. Solutions will need to incorporate both science and centuries of wine-growing knowledge. Biotechnological solutions such as using chemical analysis to detect the molecules that influence aroma are being used. The findings of these experiments could help wine-makers to more closely control the style and quality of their final product by basing decisions about harvest time on their grapes’ chemical profiles. In other regions, wine-growers are exploring solutions such as innovative soil management, changing their pruning regimes, or agroforestry, to reduce the burden of climate change.
How to train your jellyfish: brainless box jellies learn from experience
A tiny jellyfish has, for the first time, demonstrated the ability to learn by association, a type of learning made famous by neurologist Ivan Pavlov’s experiments with dogs in the late-nineteenth century. Although it has no central brain the box jellyfish (Tripedalia cystophora) can be trained to associate the sensation of bumping into something with a visual cue, and to use the information to avoid future collisions. “Associative learning is now considered solid evidence of cognitive capacity,” says Ken Cheng, an animal behaviour researcher at Macquarie University in Sydney, Australia. The jellyfish now join many other species from humans, to birds, to octopuses, and even insects, which all have the ability to learn by association.
Virus-assisted directed evolution of biomolecules
A desired biomolecule, such as a protein with specific binding properties, can be generated via diversification of a gene to generate a library of mutants, followed by the identification via either ‘screening’ or ‘selection’. ‘Screening’ is where mutants are individually assessed using a high-throughput assay. However, this restricts the sequence space that can be explored. Conversely, ‘selection’ is where desired variants are isolated using an engineered selection scheme. This works by connecting the desired function to a selectable phenotype. However, the pace of natural evolution is slow making this difficult to do in typical cells. Viruses are an interesting exception, and have the ability to evolve much more rapidly. This review discusses the recent advances on leveraging these viruses for performing novel directed evolution experiments to generate various biomolecules.
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