TRICSS - a multi-user high-throughput platform to quantify biological interactions in solution

细胞之间和细胞内的交流是通过产生配体(蛋白质、多肽、脂肪酸、类固醇和其他低分子化合物)来实现的，这些配体以特定和选择性的方式与受体分子结合。当配体与其相应的受体结合时，它会启动几种不同类型的反应，这些反应对细胞的增殖、迁移、生存和分化都是至关重要的。这一原理在医疗和工业部门得到了利用，在这些领域，药物或感兴趣的化学物质被设计成结合靶点，产生期望的生物反应(例如，抗雄激素是一类用于治疗前列腺癌的药物，其作用方式是靶向和阻断雄激素受体和/或抑制激素产生)。配体与其受体的相互作用可以用结合亲和力来表征，结合亲和力是相互作用强度的量度。了解结合亲和力是定义、建模并最终精确操纵生物过程的关键。然而，检测结合事件和精确测量相互作用的强度可能在技术上具有挑战性且耗时。与我们的学术和工业合作伙伴一起，我们想购买和使用一种新型的平板阅读器，目前在英国还没有，名为Dianses。Diansights是有史以来第一个多用户、高通量的筛选平台，使用两种生物物理模式以高灵敏度检测和量化各种配体和受体之间的真实结合事件。由石竹产生的数据的可靠性和重复性使这项技术对学术界和工业界的用户都具有极大的吸引力。事实上，结合亲和力的知识是每个药物发现过程的核心，以帮助设计有选择地和特定地结合其靶标的药物。因此，石榴花将在支持和推动许多英国生物科学计划的边界方面发挥至关重要的作用，最终以我们可能想象不到的方式让我们对生物系统有新的见解。

Communication between and within cells occurs by the production of ligands (proteins, peptides, fatty acids, steroids and other low-molecular-weight compounds) that binds in a specific and selective way to a receiving molecule, otherwise known as a receptor. When a ligand binds to its respective receptor, it initiates several different types of responses which are vital for cellular proliferation, migration, survival, and differentiation in every living organism. This principle has been exploited in the medical and industrial sectors, where a drug or a chemical substance of interest is designed to bind a target, causing a desired biological response (e.g., antiandrogens are a class of drugs used in the treatment of prostate cancer that act by targeting and blocking the androgen receptor and/or suppressing hormone production). The interaction of ligands with their receptors can be characterized in terms of a binding affinity, which is the measure of the strength of the interaction. Understanding binding affinity is key to define, model, and ultimately precisely manipulate biological processes. However, detecting binding events and precisely measuring strength of interactions can be technically challenging and time consuming. Together with our academic and industrial collaborators, we want to purchase and use a novel plate reader, currently not available in the UK, called the Dianthus. The Dianthus is the first ever multi-user, high-throughput screening platform to use two biophysical modalities to detect and quantify with high sensitivity true binding events among a diverse range of ligands and receptors. The reliability and reproducibility of data generated by the Dianthus makes this technology highly attractive to users from academia and industry alike. In fact, knowledge of binding affinities is central to every drug discovery process to help design drugs that bind their targets selectively and specifically. Thus, the Dianthus will be vital in supporting and pushing the boundaries of many UK bioscience programmes, ultimately giving us new insights into biological systems in ways we may not have thought possible.