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

课程概述：这个由MRC资助的博士培训伙伴关系(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在一起，使学生能够在与行业保持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，第一年包括一系列的教学模块和两个基于实验室的研究项目，这些项目导致了跨学科生物医学研究的硕士学位。前两个学期包括精选的教学模块，使学生能够在多学科的科学中获得坚实的基础。学生们还参加了由学术和行业专家主持的一系列大师课程，这些专家涉及分子、细胞和组织动力学、微生物学和传染病、应用生物医学技术以及人工智能和数据科学等领域。在第三学期和暑期，学生们在他们选择的实验室里进行两个为期十一周的研究项目。项目概述：传染病仍然是一个全球性的问题，由于普遍存在抗生素耐药性的日益严重的幽灵，这一问题变得更加严重。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。这包括需要治疗细菌、呼吸道和皮肤感染，这些感染会产生毒素导致疾病。人们经常认为，制药公司的化合物收藏集中在哺乳动物的靶标上，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，是结构上类似于许多常用的处方和高效的天然产物环肽抗生素的化合物。化学的可变性和识别潜在有效药物的简便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。这一合作伙伴关系使学生能够在涉及生物化学、化学、微生物学、药理学和物理学的一系列定量实验方法的广泛学科中进行培训。

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.