Manchester Chemical Biology Network

化学生物学是介于化学和生物学之间的科学领域，它使用化学工具，包括结构，物理和分析方法，以及合成小分子，以更深入地了解生物分子和生物分子系统（细胞）的功能和特性。虽然这种跨学科研究可以带来巨大的好处，特别是在医疗保健领域，但传统学科之间存在的界限阻碍了英国化学生物学的进步。2006年，曼彻斯特大学率先解决了这一问题，建立了曼彻斯特跨学科生物中心（MIB），这是英国第一个将化学家和生物学家聚集在同一栋大楼里进行研究的主要大学研究所（总共约300人）。我们建议在这个坚实的基础上，利用MIB作为一个焦点和会议场所，开发一个更广泛的化学生物学网络，将整个大学的科学家包括医学科学研究人员联合起来，他们可以进一步发展化学生物学的研究，用于医学应用。重要的是，新的曼彻斯特化学生物学网络（MCBN）将包括来自制药和生物技术行业、知识转移网络、医疗保健提供者和医疗慈善机构的合作伙伴和合作者。这些化学生物学的最终用户将有助于指导网络中的研究方向，并使我们能够建立关键的跨学科合作。如果我们要从这项研究中获得最大的利益，就必须提高我们与最终用户合作的有效性。最终，这可能包括治疗从细菌感染到癌症等人类疾病的新方法。为了使我们的研究产生最大的影响，该网络将重点关注几个关键主题。第一个主题，小分子和化学工具，将涉及基于计算的药物设计和虚拟筛选方法的开发和应用。这些活动可以帮助确定潜在的候选药物，我们将合成这些候选药物。此外，许多具有药理活性的小分子来源于天然来源（植物、土壤细菌和海洋生物）。我们将使用合成和生物合成方法生产和修饰这些天然产品。在第二个主题中，靶标调制的新概念将被开发，包括用于筛选潜在药物靶标的基于阵列的技术，其中靶标（蛋白质或低聚糖等）附着在表面上，允许高通量成像它们与其他细胞分子（包括药物）的相互作用。曼彻斯特大学开发的晶体学和核磁共振方法将与其他物理方法一起应用于探测细胞靶标的结构和动力学，这可以进一步帮助设计和优化用于治疗应用的铅分子。我们将运用我们在酶学（酶是如何工作的）和细胞生物学（人类细胞的复杂成分是如何相互作用的）方面的知识来发现新的酶，其他生物分子靶点和治疗干预途径，我们将用我们的小分子武器库等进行研究。在第三个主题中，目标反卷积，我们将采用系统生物学方法，该方法模拟细胞中的所有成分，并允许解释细胞对非生物物质（例如药物）的更广泛反应。这对于预测药物可能的毒副作用尤其重要。最后一个主题是大分子和小分子的交叉，我们将开发新的方法来改善用作治疗剂（生物制药）的蛋白质和抗体的特性。我们还将开发新的药物输送系统，使用纳米颗粒和其他智能材料，将药物靶向并释放到特定的病变细胞中，而不是健康细胞中。

Chemical biology is the area of science at the interface between chemistry and biology, which uses chemical tools including structural, physical and analytical methodologies as well as synthetic small molecules to gain deeper insight into the function and properties of biomolecules and biomolecular systems (cells). Whilst great benefit can be derived from such interdisciplinary research, particularly in the area of healthcare, boundaries that exist between traditional disciplines have hindered the progress of chemical biology in the UK. In 2006, the University of Manchester took the lead in addressing this issue by establishing the Manchester Interdiscplinary Biocentre (MIB), which was the first major university institute in the UK to bring chemists and biologists together to do research in the same building (ca. 300 in total). We propose to build on this solid foundation, using MIB as a focal point and meeting place, to develop a much wider chemical biology network that unites scientists from across the university including researchers in medical science who can further develop research in chemical biology for medical applications. Importantly, the new Manchester Chemical Biology Network (MCBN) will include partners and collaborators from the pharmaceutical and biotechnology industry, knowledge transfer networks, healthcare providers and medical charities. These end users of chemical biology will help guide the direction of the research in the network and enable us to establish critical cross-discplinary collaborations. Increasing the effectiveness of our collaborations with the end users will be essential if we are to see maximum benefit derived from this research. Ultimately this could include new approaches for the treatment of human disease ranging from bacterial infections through to cancer. To enable maximum impact from our research to be realised, the network will focus on several key themes. The first theme, small molecules and chemical tools, will involve the development and application computational based approaches for drug design and virtual screening. Such activities can help identify potential drug candidates, which we will synthesise. Also many pharmacologically active small molecules are derived from natural sources (plants, soil bacteria and marine organisms). We will produce and modify these natural product leads using synthetic and biosynthetic methods. In the second theme, new concepts in target modulation will be developed including array based technologies for screening potential drug targets, where targets (proteins or oligosaccharides etc.) are attached to surfaces allowing high throughput imaging of their interactions with other cellular molecules including drugs. Crystallography and NMR methods, developed in Manchester, along with other physical methods will be applied to probe the structure and dynamics of cellular targets, which can further help in the design and optimisation of lead molecules for therapeutic applications. We will apply our knowledge of enzymology (how enzymes work) and cell biology (how the complex components of human cells interact) to uncover new enzymes, other biomolecular targets and pathways for therapeutic intervention, which we will interrogate with our arsenal of small molecules etc. In the third theme, target deconvolution, we will take a systems biology approach, which models all the components in the cell and allows the broader response of cells to abiotic substances (e.g. drugs) to be interpreted. This can be particularly important for predicting possible toxic (side) effects of drugs. In the final theme, intersection of large and small molecules, we will develop new methods for improving the properties of proteins and antibodies for use as therapeutic agents (biopharmaceuticals). We will also develop new drug delivery systems using nanoparticles and other smart materials programmed to target and release drugs in specific diseased cells, but not healthy cells.