Geometry as a key to the virosphere: Unmasking the fundamental roles of geometry in virus structure, evolution and pathology

社会面临着来自病毒性疾病的重大挑战。最近的寨卡和埃博拉疫情只是病毒性疾病对人类健康造成破坏性影响的两个例子，感染农业重要牲畜和植物的病毒病原体同时减少粮食产量，并在全球范围内造成巨大的年度经济损失。然而，病毒也对健康和生态产生积极影响。它们平衡和稳定我们的肠道微生物组，预防某些自身免疫性疾病等严重疾病，并由于它们在海洋碳循环中的作用而影响我们的气候。因此，为了在医学和生物技术中控制甚至利用病毒，更好地了解整个病毒圈的病毒结构和功能至关重要。我以前已经证明，与实验学家一起开发的数学方法是发现功能关键的结构病毒特征的驱动力，揭示了它们在病毒生命周期中的新功能作用，并使它们能够在治疗和生物技术中利用。以前开发的数学方法是面向一个特定的主要亚组的病毒层。在这项研究计划中，我将扩大和深化新的数学技术的发展。与领先的实验组密切合作，在更大的规模上，我将在一些主要的病毒组中识别功能重要的病毒几何特征。这将包括：多体病毒中的几何链分类，如主要农业病原体蓝舌病毒;逆转录病毒如HIV的组装，应用于从病毒组分构建病毒样颗粒作为基因编辑和治疗的载体;以及对肠道微生物组和海洋生态重要的病毒的结构和进化。通过将结构特征与它们的功能联系起来，我将解决关于生物实体中最简单但最重要的群体之一的进化驱动力的开放问题。这种方法将揭示进化上保守的功能特征，这些功能特征可用作抗病毒治疗的新靶点，用于开发新的更安全的疫苗或在生物纳米技术中重新利用。

Society faces major challenges from viral diseases. The recent Zika and Ebola outbreaks are only two examples of the devastating impact of viral illnesses on human health, and viral pathogens infecting agriculturally important livestock and plants simultaneously reduce food production and inflict great annual financial losses worldwide. Viruses, however, also have positive impacts on health and ecology. They balance and stabilise our gut microbiome, preventing serious illnesses such as certain autoimmune diseases, and influence our climate owing to their roles in carbon cycling in the oceans. It is therefore paramount to better understand virus structure and function across the entire virosphere in order to control, and even take advantage of, viruses in medicine and biotechnology. I have demonstrated previously that mathematical approaches developed in tandem with experimentalists are drivers of discovery of functionally crucial structural viral features, revealing their novel functional roles in viral life cycles, and enabling their exploitation in therapy and biotechnology. Previously developed mathematical approaches were geared towards a specific major sub-group of the virosphere. In this research programme, I will both broaden and deepen the development of novel mathematical techniques. Working in close collaboration with leading experimental groups, at a larger scale, I will identify functionally important geometric viral features in a number of major groups of viruses. This will include: geometric strand assortment in multipartite viruses, such as the major agricultural pathogen Bluetongue virus; the assembly of retroviruses like HIV, with applications to the construction of virus-like particles from viral components as vectors for gene editing and therapy; and the structure and evolution of viruses important for the gut microbiome and marine ecology. By linking structural features with their functions, I will address open problems regarding drivers of evolution in one of the simplest yet most important groups of biological entities. This approach will unmask evolutionarily conserved functional features that can be used as novel targets in anti-viral therapy, for the development of novel safer vaccines or repurposed in bionanotechnology.