Bicyclic peptides: targeting toxins and pathogens to accelerate anti-infective discovery

项目概述：这个mrc资助的博士培训合作伙伴关系（DTP）将尖端的分子和分析科学与数据分析中的创新计算方法结合起来，使学生能够在与行业一致的优先领域解决重要的应用生物医学研究问题。这是一个为期4年的课程，第一年包括一系列教学模块和两个基于实验室的研究项目，最终获得跨学科生物医学研究硕士学位。前两个学期包括一系列教学模块，让学生在多学科科学方面打下坚实的基础。学生还将参加一系列由分子、细胞和组织动力学、微生物学和感染、应用生物医学技术、人工智能和数据科学等领域的学术和行业专家主持的大师班。在第三学期和夏季学期，学生在他们选择的实验室进行两个为期11周的研究项目。项目概述：传染病仍然是一个全球性问题，由于广泛存在的抗生素耐药性的幽灵越来越大，情况变得更加严重。这减少了我们的治疗选择，意味着我们需要新的创新药物来治疗感染。这包括需要治疗产生毒素导致疾病的呼吸道和皮肤细菌感染。人们经常认为，制药公司的化合物集中在哺乳动物靶点上，缺乏具有成功抗生素典型结构特征的化合物。在这里，我们正在寻找一种新的方法来靶向和中和这些毒素和细菌，这些毒素和细菌会导致包括肺炎和败血症在内的重要疾病。这些化合物被称为自行车，它们的结构与许多常用的高效天然产品环肽抗生素相似。化学的可变性和识别那些潜在有效的药物的便捷性使它们成为设计下一代抗菌药物的理想模板。随着抗菌素耐药性威胁的迅速增长，迫切需要这种新的抗感染产品。这将由华威大学的学者和我们在剑桥的行业合作伙伴共同完成。这种合作关系使学生能够在广泛的学科中接受培训，涉及生物化学、化学、微生物学、药理学和物理学等一系列定量实验方法。

Programme overview:This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address important applied biomedical research questions in priority areas aligned with industry. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice. Project overview:Infectious diseases are still a global problem, made worse by the growing spectre of widespread antibiotic resistance. This has reduced our options for treatment and means that we need new innovative drugs to treat infections. This includes the need to treat bacterial respiratory and skin infections which produce toxins to cause disease. It is often argued that the compound collections of pharmaceutical companies are focussed around mammalian targets and lack compounds with structural features typical of successful antibiotics. Here we are looking at a new approach to target and neutralize these toxins and bacteria that cause important diseases including pneumonia and sepsis. These compounds are called Bicycles, and are compounds that are structurally similar to many of the commonly prescribed and highly effective natural product cyclic peptide antibiotics. The chemical variability and ease of identifying those that are potentially effective makes them ideal templates for the design of next generation antibacterial drugs. With the rapidly growing threat of antimicrobial resistance, such new anti-infective products are urgently needed. This will be done collaboratively between academics at Warwick and our industry partner in Cambridge. The partnership enables student training in a wide range of disciplines involving a range of quantitative experimental approaches across biochemistry, chemistry, microbiology, pharmacology and physics.