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

TRICSS - 一个多用户高通量平台，用于量化溶液中的生物相互作用

• 批准号: BB/X018997/1
• 负责人: Filippo Prischi
• 金额: $ 48.84万
• 依托单位: University of Essex
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX018997%2F1
• 关键词: TRICSS; multi; user; throughput; platform

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.

细胞之间和细胞内的通讯是通过产生配体（蛋白质、肽、脂肪酸、类固醇和其他低分子量化合物）来进行的，这些配体以特异性和选择性的方式与接收分子（也称为受体）结合。当配体与其各自的受体结合时，它会引发几种不同类型的反应，这些反应对于每个生物体中的细胞增殖，迁移，存活和分化至关重要。这一原理已经在医学和工业领域得到利用，其中感兴趣的药物或化学物质被设计为结合靶标，引起期望的生物反应（例如，抗雄激素是一类用于治疗前列腺癌的药物，其通过靶向和阻断雄激素受体和/或抑制激素产生而起作用）。配体与其受体的相互作用可以根据结合亲和力来表征，其是相互作用强度的量度。理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者一起，我们想购买和使用一种新的读板器，目前在英国还没有，称为石竹。Dianthus是第一个多用户高通量筛选平台，使用两种生物物理模式来检测和定量各种配体和受体之间的高灵敏度真实结合事件。石竹产生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极具吸引力。事实上，结合亲和力的知识是每一个药物发现过程的核心，有助于设计选择性和特异性结合靶点的药物。因此，石竹将在支持和推动许多英国生物科学计划的界限方面至关重要，最终以我们可能想不到的方式为我们提供对生物系统的新见解。