Development of the Gastrobody platform to combat Clostridium perfringens toxins

开发 Gastrobody 平台来对抗产气荚膜梭菌毒素

基本信息

批准号：
BB/W014297/1
负责人：
Mark Howarth
金额：
$ 73.11万
依托单位：
University of Cambridge
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
起止时间：
2023 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FW014297%2F1
关键词：
Development Gastrobody platform combat Clostridium

项目摘要

Antibodies are proteins that can bind specific targets such as bacteria, viruses or toxins to stop them causing disease. Antibodies are not widely used in agriculture because, like nearly all proteins in the diet, they are quickly destroyed by the stomach and small intestine. We have generated "gastrobodies" by engineering a protein from soybeans to bind new targets. Unlike antibodies or other protein scaffolds, gastrobodies are highly resistant to the harsh digestive enzymes of the gut. Here we will test the ability of gastrobodies to protect against bacterial disease. Clostridium perfringens is a bacterium that causes a wide range of diseases affecting farmers, including in pigs, cows, sheep and chickens. These effects are caused by toxins released by the bacterium. We will establish gastrobodies that can stop these bacterial toxins in the gut from causing damage. We will focus on the toxins that cause necrotic enteritis in chickens, which has increased dramatically following the banning of antibiotics in animal feed and costs billions of pounds per year worldwide. We aim to establish the cost-effective production of gastrobodies, so that they can be simply added to animal feed and then recognise specific targets within the digestive system. These goals should set the stage for broad use of gastrobodies for gut health, with relevance to many agricultural and medical diseases.

抗体是可以结合特定靶标，例如细菌，病毒或毒素的蛋白质，以阻止它们引起疾病。抗体并未在农业中广泛使用，因为像饮食中几乎所有蛋白质一样，它们很快被胃和小肠破坏。我们通过从大豆上设计蛋白质来结合新靶标，从而产生了“胃药”。与抗体或其他蛋白质支架不同，胃药对肠道的苛刻消化酶具有高度抗性。在这里，我们将测试胃生物学预防细菌疾病的能力。灌注梭菌是一种细菌，可引起各种影响农民的疾病，包括猪，牛，绵羊和鸡。这些作用是由细菌释放的毒素引起的。我们将建立可以阻止肠道中这些细菌毒素造成损害的胃结构。我们将重点关注引起鸡坏死性肠炎的毒素，在动物饲料中禁止抗生素和全球每年数十亿英镑之后，鸡的毒素大大增加了。我们旨在建立胃药的具有成本效益的产生，以便可以简单地将它们添加到动物饲料中，然后识别消化系统中的特定靶标。这些目标应该为肠胃健康的广泛使用，与许多农业和医疗疾病有关。