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

细胞之间和细胞内部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量化合物）来实现的，这些配体以一种特定的、选择性的方式与接收分子结合，也就是我们所说的受体。当配体与相应的受体结合时，它会启动几种不同类型的反应，这些反应对每个生物体的细胞增殖、迁移、存活和分化至关重要。这一原则已在医疗和工业部门得到利用，在这些部门中，感兴趣的药物或化学物质被设计成与目标结合，引起所需的生物反应（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/或抑制激素的产生）。配体与其受体的相互作用可以用结合亲和力来表征，这是相互作用强度的度量。理解结合亲和力是定义、建模和最终精确操纵生物过程的关键。然而，检测绑定事件和精确测量相互作用的强度在技术上具有挑战性，而且耗时。与我们的学术和工业合作者一起，我们想购买和使用一种新颖的车牌阅读器，目前在英国不可用，称为Dianthus。Dianthus是有史以来第一个多用户，高通量筛选平台，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正结合事件。Dianthus生成的数据的可靠性和可重复性使这项技术对学术界和工业界的用户都具有很高的吸引力。事实上，结合亲和力的知识是每个药物发现过程的核心，有助于设计有选择性和特异性结合靶标的药物。因此，石蜡将在支持和推动许多英国生物科学项目的边界方面发挥至关重要的作用，最终以我们可能认为不可能的方式为我们提供对生物系统的新见解。

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.