MRC TS Award: Regulation of neutrophil functions by cell cycle proteins

MRC TS 奖：细胞周期蛋白调节中性粒细胞功能

• 批准号: MR/X023087/1
• 负责人: Borko Amulic
• 金额: $ 61.89万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX023087%2F1
• 关键词: MRC; TS; Award; Regulation; neutrophil

Neutrophils are the most abundant immune cells in the blood and they are essential for defending us against disease-causing microbes. They are considered the 'first line of defence' in response to infection or wounding. Neutrophils have several ways of destroying microbes to prevent the infection from spreading. They can engulf microbes or produce antimicrobial chemicals. Neutrophils can also release "NETs" - Neutrophil Extracellular Traps. NETs consist of webs of DNA that are adhesive and also contain toxic antimicrobial proteins; NETs trap microbes and prevent them from spreading away from the site of infection. They also help to amplify inflammation and to recruit additional immune cells.NET release must be carefully controlled because excessive NET formation can also damage our own cells and tissues. In fact, neutrophils are often hyperactivated in many non-infectious inflammatory diseases. Excessive NET formation is thought to contribute to autoimmune diseases such as lupus, rheumatoid arthritis and asthma, as well as cancer and atherosclerosis (which can cause stroke and heart attack).If we could understand how NETs formation is regulated, we could potentially develop therapies to boost NET formation when the body needs to prevent infections or, conversely, to block their release when they are causing pathological inflammation. The aim of this proposal is to complete undergoing studies that aim to understand which proteins control NET release. We discovered that some proteins that normally control cell division are also involved in regulating NET formation. We now propose to undertake detailed studies to understand exactly how these proteins function in NET formation. We will do this by analysing which additional proteins the regulators interact with, and what aspects of cellular biology they affect.Completing these aims will give us a better understanding of the molecular mechanism of NETs. It would also help to establish my group as international experts in the field of neutrophil biology, allowing us to tackle important global health issues.

嗜中性粒细胞是血液中最丰富的免疫细胞，它们对于捍卫我们免受引起疾病的微生物至关重要。它们被认为是对感染或伤害的“第一道防线”。中性粒细胞有几种破坏微生物以防止感染扩散的方法。它们可以吞噬微生物或产生抗菌化学物质。中性粒细胞还可以释放“网” - 中性粒细胞外陷阱。网络由粘合剂的DNA网组成，还包含有毒的抗菌蛋白；净捕获微生物，并防止它们从感染部位散开。它们还有助于扩大炎症并募集其他免疫细胞。必须仔细控制NET释放，因为净形成过多也会损害我们自己的细胞和组织。实际上，在许多非感染性炎症性疾病中，中性粒细胞通常会过度激活。人们认为过度的网络形成会导致狼疮，类风湿关节炎和哮喘等自身免疫性疾病，以及癌症和动脉粥样硬化（这可能引起中风和心脏病发作）。如果我们可以了解网络形成如何受到调节，那么我们可以在身体上逐渐释放出来，以阻止他们释放出来的疗程，以促进他们的释放，以阻止他们的释放，从而阻止了他们的疾病，因此可以促进他们的疾病，从而阻碍了他们的交流。该提案的目的是完成旨在了解哪些蛋白质控制净释放的研究。我们发现一些通常控制细胞分裂的蛋白质也参与调节净形成。现在，我们建议进行详细的研究，以准确了解这些蛋白质如何在净形成中起作用。我们将通过分析调节剂与哪些其他蛋白质相互作用以及细胞生物学的哪些方面来做到这一点。这也将有助于建立我的小组成为中性粒细胞生物学领域的国际专家，从而使我们能够解决重要的全球健康问题。