Structural Fundamentals of Gliding Motility
Structural Fundamentals of Gliding Motility
批准号:
BB/X006298/1
负责人:
Andrew Lovering
金额:
$55.52万
依托单位:
依托单位国家:
英国
项目类别:
Research Grant
财政年份:
2023
资助国家:
英国
项目状态:
未结题
起止时间:
2023 至 --
中文摘要
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英文摘要
Movement has a huge role to play in all aspects of cellular life: escape from harm, colonizing hosts in disease, moving towards a food source - anything where an advantage can be gained by changing environment. Currently there is a bias in what we know about the different modes of cellular motility, for example we have an excellent molecular understanding of swimming (via a rotary "tail"-like apparatus called the flagellum) and slingshot crawling (via a grappling hook like apparatus called the type 4 pilus). Conversely, we know very little about how bacterial gliding works, a means of motility where the cell slides on a surface with no visible clues as to how propulsion is achieved.We do however know the genes involved, and these are often present in predatory bacteria, specialized organisms that use gliding to hunt and kill their fellow bacteria. One of these predators, Bdellovibrio (our organism of choice for this study) may even prove useful in killing the antibiotic resistant bacteria that are an emerging problem in healthcare. An improved understanding of gliding would lead us to understand predators better, particularly in terms of how they navigate prey-rich surfaces known as biofilms. Besides healthcare, there may be applications for Bdellovibrio and related predators in crop pestilence, food safety, biofouling and water treatment.Our investigation here aims to validate a model in which we have pieced together several identified gliding components (proteins) around a common hub that aims to organize these in conveying energy from inside the cell to a means of propulsion outside the cell. Excitingly, our preliminary studies provide intuitive roles for each of the pieces, and suggest that the adhesive part is related to a known system from human cells - hence there may be an evolutionary link where bacterial movement was the progenitor for other systems. This will be driven by structural and biochemical understanding of how the gliding proteins fit together and interact with one another, which should also involve several states/poses that ultimately tell us how the machinery works.Results from our study will be "first-in-class", as nothing is currently known about the molecular details of the gliding machinery. The work will have broad impact - there will be key similarities and differences to other modes of movement that will enrich our understanding (as well as stimulating the direct field of predatory bacteria).
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