Rachael Walker

Streptococcal pneumonia is a worldwide health problem that kills ∼2 million people each year, particularly young children, the elderly, and immunosuppressed individuals. Alveolar macrophages and neutrophils provide the early innate immune response to clear pneumococcus from infected lungs. However, the level of neutrophil involvement is context dependent, both in humans and in mouse models of the disease, influenced by factors such as bacterial load, age, and coinfections. Here, we show that the G protein-coupled receptor (GPCR) adaptor protein norbin (neurochondrin, NCDN), which was hitherto known as a regulator of neuronal function, is a suppressor of neutrophil-mediated innate immunity. Myeloid norbin deficiency improved the immunity of mice to pneumococcal infection by increasing the involvement of neutrophils in clearing the bacteria, without affecting neutrophil recruitment or causing autoinflammation. It also improved immunity during Escherichia coli-induced septic peritonitis. It increased the responsiveness of neutrophils to a range of stimuli, promoting their ability to kill bacteria in a reactive oxygen species-dependent manner, enhancing degranulation, phagocytosis, and the production of reactive oxygen species and neutrophil extracellular traps, raising the cell surface levels of selected GPCRs, and increasing GPCR-dependent Rac and Erk signaling. The Rac guanine-nucleotide exchange factor Prex1, a known effector of norbin, was dispensable for most of these effects, which suggested that norbin controls additional downstream targets. We identified the Rac guanine-nucleotide exchange factor Vav as one of these effectors. In summary, our study presents the GPCR adaptor protein norbin as an immune suppressor that limits the ability of neutrophils to clear bacterial infections.

Undoubtedly, the global pandemic caused by the SARS-CoV-2 virus has had a significant impact on Shared Resource Laboratories (SRL) operations worldwide. Unlike other crises (e.g. natural disasters, acts of war, or terrorism) which often result in a sudden and sustained cessation of scientific research usually affecting one or two cities at a time, this impact is being seen simultaneously in every SRL worldwide albeit to a varying degree. The alterations to SRL operations caused by the COVID-19 pandemic can generally be divided into three categories: i) complete shutdown, ii) partial shutdown, and iii) uninterrupted operations. In many cases SRLs which remained partially or fully operational during the initial wave of global infections saw a concurrent increase in COVID-19-related research coming through their facilities. This forced SRLs to make rapid adjustments to core operations at the same time as infectious disease experts were still developing recommendations for the safety of frontline medical workers. Although many SRLs already had contingency plans in place, this pandemic has highlighted the importance of having such plans for continuity of service, if possible, during a crisis. Immediate changes have occurred in the way SRLs operate due to potential virus transmission and in line with this new "Best Practices" have been established i.e. social distancing, remote working and technology-based meetings and training. Many of these changes are likely to be in place for some time with the threat of further waves of infections toward the end of 2020 and into 2021. Some of these best practices, such as having many training resources recorded and available online, are likely to remain long term. Although many changes have been made in haste, these will alter the future operations of SRLs. In addition we have learnt how to deal with future crises that may be encountered in the workplace.

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