Research and use of high-throughput robotic screens to identify fucoidanases and sulfatases from marine environments

研究和使用高通量机器人屏幕识别海洋环境中的岩藻聚糖酶和硫酸酯酶

• 批准号: 486082-2015
• 负责人: Withers, Stephen
• 金额: $ 1.82万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=585386
• 关键词: Research; use; throughput; robotic; screens

Fucoidan is a polysaccharide found in seaweed that has been found, by ARC Medical Devices Inc., to be very effective in reducing adhesion developments in the abdominal cavities of animals after surgery. The success of this product in veterinary use has prompted a desire to develop the product for use in humans. Currently ARC purchases the fucoidan, but the material obtained is of heterogeneous composition. In order to move the product into the human market, they need to develop means to improve homogeneity and purity, and to lower the average molecular weight. Two routes are possible: modifying and purifying the commercial fucoidan, or enzymatically synthesising custom fucoidan from pure simple starting materials. The most practical way towards both ends is to first find enzymes that can degrade fucoidan, and use these to generate material of the desired size, then purify this lower molecular weight material. The other would be to engineer these degradative enzymes into synthetic enzymes and use these to assemble fucoidan of the desired properties. This is however challenging as no fucoidanases have ever been isolated and cloned to our knowledge, but such enzymes must exist. Several approaches to this are possible. Our approach is to screen both libraries of marine bacteria and fragments of genes from marine sources, some of which may well use seaweed as a food source, to look for fucoidanase activity. We shall then identify the responsible genes and from them produce the enzymes to test whether they can carry out the desired task. Successful completion of the project will lead to a process to produce a novel, first in class medical device for the reduction of post-surgical adhesions in humans, which in turn will reduce pain, suffering, infertility and mortality in Canadian patients following common surgical procedures; reduce Canadian hospital stays, hospital re-admissions, and re-operations, which in turn will reduce healthcare costs for Canadian governments and taxpayers; and create scientific, manufacturing and sales jobs within Canada, and export of a high margin product.

岩藻依聚糖是一种在海藻中发现的多糖，ARC医疗器械公司已经发现，非常 有效减少手术后动物腹腔内粘连的发展。的成功 该产品在兽医中的应用促使人们希望开发该产品用于人类。目前ARC 购买岩藻依聚糖，但获得的材料具有异质组成。 为了将产品推向人类市场，他们需要开发改善同质性的手段， 纯度和降低平均分子量。两种途径是可能的：修饰和纯化 商业岩藻依聚糖，或从纯的简单起始材料酶促合成定制岩藻依聚糖。的 最实用的方法是首先找到可以降解岩藻依聚糖的酶，并使用这些酶来 生成所需尺寸的材料，然后纯化该较低分子量的材料。另一个是 将这些降解酶改造成合成酶并使用它们来组装所需的岩藻依聚糖 特性.然而，这是具有挑战性的，因为还没有岩藻聚糖酶被分离和克隆到我们的细胞中。 知识，但这种酶必须存在。对此有几种可能的方法。我们的方法是筛选 海洋细菌文库和海洋来源的基因片段，其中一些可能很好地利用了 海藻作为食物来源，以寻找岩藻聚糖酶活性。然后，我们将确定负责的基因， 从它们中产生酶来测试它们是否能完成所需的任务。成功完成 该项目将导致一个过程，以生产一种新型的，一流的医疗设备，以减少 手术后粘连，这反过来将减少疼痛，痛苦，不孕症和死亡率， 接受普通外科手术的加拿大患者;减少加拿大住院时间， 再次入院和再次手术，这反过来将降低加拿大政府的医疗保健成本， 纳税人;并在加拿大境内创造科学，制造和销售工作，以及高利润率的出口 产品