Why do children experience milder COVID?
For most of 2020, there wasn’t even 1 paediatric case of COVID that was admitted to an ICU in Hong Kong. However, nobody really knows why children have a milder immune response to the coronavirus. In this study, the authors measure the serum level of antibodies targeted at Coronavirus Spike and Nucleocapsid proteins of adults and children from New York, and observe that the levels and types of antibodies in children are much less than adults. To perform an analysis like this, biologists use linear regression in order to correct for various factors that may confound the results (eg time post-symptom onset, and ironically: age), and thus correct for other factors that may influence the measurements aside from being an adult or a kid. Interestingly, the results show that the paediatric response to the coronavirus is not associated with the development of widespread inflammation-associated immunogenic disease, which seems to hint at the possibility of a different mechanism that underlies the paediatric response. However, it should be noticed that the sample size of 79 individuals is not sufficient for a definitive study, and the use of pseudovirus assays adds layers of uncertainty to the results. (Weisberg et al., 2020)
Modern anatomical research
Understanding anatomy forms the basis of medicine – the structures and categorisations of cells allow us to form coherent molecular theories on the processes that underly disease. Moving on from microscopes, the authors utilised single-cell RNA sequencing to categorise cells in lungs. Due to the complicated protein folding, it is difficult to identify the sequences of all cellular proteins accurately. Therefore, scientists choose to sequence the RNA in a cell in order to predict which proteins are effectively expressed. Here, the authors are able to identify 58 types of lung cells with unprecedented accuracy and efficacy, and provides further detail into the varying levels of expression of different chemicals in different cells to aid further research and theory development. (Travaglini et al., 2019)
Elucidating cellular structures
In contrast to the well-laid out structures that High-School presents, research in cellular biology often follows a more treacherous path. Biologists often first notice a correlation between a certain protein and a certain emergent property, in this case the suppression of MFSD12 and the darker pigmentation in cells. Then, biologists can apply laboratory techniques, first by isolating the organelle in question with centrifugation or targeted labelling, then running tests either with recognisable isotyped molecules or tagged antibodies. In this case, the melanosome was isolated and cystine transport rate was quantified with incubation of 14C cystine. Lastly, biologists may verify their findings by applying the same hypothesis to diseases known-to involve said protein, which in this case is the reduction of pathogenic accumulation of cystine in cystinosis patients with mutated MFSD12. As biologists delve further into the specific functioning of different organelles, we begin to understand how much we still do not understand about how our body functions on a cellular level. (Adelmann et al., 2020)
Nature’s electrical engineering
Our brain functions by connecting neurons and creating electrical circuits, so that the variations in combinations of the 86 billion neurons can create human thought. To construct these electrical circuits, a multitude of proteins are needed to transport ions, signal chemicals (neurotransmitters) and enzymes (helping to construct/ degrade neurotransmitters). In this paper, the authors explore how 2 proteins (SYD-2 and ELKS-1) are first phase-separated (like oil and water), and then formed into a solid at the right moment, which supports the scaffold shape of neurons.
The authors found that protein motifs and other mutually-intelligible sections of protein structures could be substituted for some parts of these proteins, which demonstrates how protein language is like human language – with words and phrases that have evolved to be recognised by others.
The growing field of biophysics also offers molecular biology a new way to view the cell, with the interaction between liquids, solutions, colloids and solids paving the way to a compartmentalised cell that may not be organised simply by morphological features. Processes of phase separation and liquid-liquid interfaces allow the cytoplasm to organise itself without the need of organelles. (McDonald et al., 2020)
Working out how enzymes work
Researching the functioning of enzymes in diseases provides more practical applications and also makes it much easier to find funding; in this article, the authors investigate the functioning of 2 enzymes that have been observed to destroy the harmful amyloid fibrils that cause Parkinson’s disease. To elucidate the mechanism of action of enzymes, biologists can alter the functionality of different parts of different proteins, and then observe the resulting products to work out what happened. Here, the authors introduced a version of the proteins that were unable to dimerise, and observed the inability of the mixture to dissolve the amyloid fibrils, and thus could prove that dimerisation was essential for the enzymes to work. With more laboratory measurements on the emission of fluorescent light as substrates are gradually added to the setups, biologists figured out that these enzymes were co-chaperones – enzymes that work to move amyloid fibrils to the enzyme that actually does the degradation, and once again demonstrates how synergistic chaperones are real-life examples of how 1+1>2. (Wentink et al., 2020)
References:
Adelmann, C. H., Traunbauer, A. K., Chen, B., Condon, K. J., Chan, S. H., Kunchok, T., Lewis, C. A., & Sabatini, D. M. (2020). MFSD12 mediates the import of cysteine into melanosomes and lysosomes. Nature, December 2019. https://doi.org/10.1038/s41586-020-2937-x
McDonald, N. A., Fetter, R. D., & Shen, K. (2020). Assembly of synaptic active zones requires phase separation of scaffold molecules. Nature, April. https://doi.org/10.1038/s41586-020-2942-0
Travaglini, K., Nabhan, A., Penland, L., Sinha, R., Gillich, A., Sit, R., Chang, S., Conley, S., Mori, Y., Seita, J., Berry, G., Shrager, J., Metzger, R., Kuo, C., Neff, N., Weissman, I., Quake, S., & Krasnow, M. (2019). A molecular cell atlas of the human lung from single cell RNA sequencing. 587(August 2019). https://doi.org/10.1101/742320
Weisberg, S. P., Connors, T. J., Zhu, Y., Baldwin, M. R., Lin, W.-H., Wontakal, S., Szabo, P. A., Wells, S. B., Dogra, P., Gray, J., Idzikowski, E., Stelitano, D., Bovier, F. T., Davis-Porada, J., Matsumoto, R., Poon, M. M. L., Chait, M., Mathieu, C., Horvat, B., … Farber, D. L. (2020). Distinct antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum. Nature Immunology 2020, 1–7. https://doi.org/10.1038/s41590-020-00826-9
Wentink, A. S., Nillegoda, N. B., Feufel, J., Ubartaitė, G., Schneider, C. P., De Los Rios, P., Hennig, J., Barducci, A., & Bukau, B. (2020). Molecular dissection of amyloid disaggregation by human HSP70. Nature, January. https://doi.org/10.1038/s41586-020-2904-6
Comments