Olds, J. L. | Search bioRxiv

bioRxiv2021

Mechanisms of Coupling between Angiotensin Converting Enzyme 2 and Nicotinic Acetylcholine Receptors

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus encapsulated by a spike (S) glycoprotein envelope, binds with high affinity to angiotensin converting enzyme 2 (ACE2) during cell entry of a susceptible host. Recent studies suggest nicotinic acetylcholine receptors (nAChRs) play a role in functional ACE2 regulation and nicotine may contribute to the progression of coronavirus disease 2019 (COVID-19). Here, we present evidence for coupling between ACE2 and nAChR through bioinformatic analysis and cell culture experiments. Following molecular and structural protein comparison of over 250 ACE2 vertebrate orthologues, a region of human ACE2 at positions C542-L554 was identified to have sequence similarity to nAChR-binding neurotoxin and rabies virus glycoproteins (RBVG). Furthermore, experiments conducted in PC12 cells indicate a potential for physical interaction between ACE2 and 7 nAChR proteins. Our findings support a model of nAChR involvement in in COVID-19.

neuroscience↗

bioRxiv2019

Establishing BARA: Biological Nitrogen Fixation for Future Agriculture

The extensive use of nitrogen (N) fertilizers implicates a paradox. While fertilizers ensure the supply of a large amount of food, they cause negative environmental externalities including reduced biodiversity, eutrophic streams, and lakes. Moreover, such fertilizers may also result in a major public health hazard: increased antibiotic resistance. This Perspective discusses a critical role of perturbations in N cycle caused by excessive use of fertilizers and resulting implications as they relate to resistance genes and biodiversity in the biosphere. While there are solutions such as cover crops, these solutions are expensive and inconvenient for farmers. We advocate the use of biological fixation for staple crops--microbiome mediated natural supply of fixed N. This would involve engineering a microbiome that can be grown cheaply and at scale (less expensive than Haber-Bosch fertilizers). We also propose a practical framework of where and how research investments should be directed to make such a solution practical. We make three recommendations for decision makers to facilitate a successful trajectory for this solution. First, that future agricultural science seek to understand how biological fixation might be employed as a practical and efficient strategy. This effort would require that industries and government partner to establish a pre-competitive research laboratory equipped with the latest state-of-the-art technologies that conduct metagenomic experiments to reveal signature microbiomes. Second, the Department of Agriculture and state governments provide research and development (R & D) tax credits to biotech companies specifically geared towards R&D investments aimed at increasing the viability of biological fixation and microbiome engineering. Third, governments and the UN Food and Agriculture Organization (FAO) coordinate Biological Advanced Research in Agriculture (BARA)--a global agricultural innovation initiative for investments and research in biological fixation and ethical, legal, and social implications of such innovation.

microbiology↗