Novel nanoplasmonic sensors for non-invasive detection of senescence

这个为期3.5年的学生是谢菲尔德大学健康寿命研究所（HELSI）的一部分。HELSI致力于了解和预防多重疾病（存在两种或两种以上造成残疾和降低生活质量的慢性健康状况）。我们正在采取一种独特的多学科方法来帮助人们活得更长，更健康，更独立的生活。健康寿命研究所的学生是研究所的重要和积极的成员，对我们的目标做出贡献并帮助实现真实的变化至关重要。您将成为博士生更广泛的多学科网络的一部分（见此处），并将有机会影响和领导研究所的活动，研讨会和活动，并在该领域会见领导人。世界卫生组织（WHO）最近发布的一份关于健康老龄化的报告开始说：“世界正面临着前所未有的局面：我们很快就会有更多的老年人超过儿童，而且比以往任何时候都有更多的极端老年人。“这充分说明了健康老龄化研究的重要性。其中一个备受关注的研究领域是，使用专门杀死衰老细胞或改变其分泌物的“衰老”药物，消除“僵尸”细胞（称为衰老细胞）的潜力，这些细胞随着年龄的增长而积累，并导致慢性炎症和许多衰老疾病。几项使用衰老治疗药物的动物研究显示出惊人的结果，寿命延长，与年龄相关的疾病减少。然而，由于缺乏衰老细胞负荷的非侵入性、特异性生物标志物，这一转化严重阻碍了人类。确定可靠的药效学生物标志物非常重要，因为它可用于对潜在临床终点（包括患者安全性）的治疗效果进行早期评估。细胞外囊泡（EV）是由细胞释放到周围环境中的小的膜结合结构，并且在所有体液中丰富。它们含有各种核酸、脂质和蛋白质，这些核酸、脂质和蛋白质提供了它们所来源的细胞的特征。鉴于人们对衰老细胞与增殖细胞相比分子结构变化的理解不断加深，这提出了一个诱人的前景，即体液中存在的EV可能有望作为衰老的生物标志物，并且可以利用这一点开发非侵入性、低成本的衰老细胞负荷测定方法。项目目标：我们提出了一种简单，灵敏的测定方法，其基于对衰老细胞衍生的细胞外囊泡的纳米等离子体分析，可以确定衰老细胞负荷并改变senotherapeutics的临床翻译。在这个项目中，我们提出了两种新的方法来检测衰老的生物标志物，基于衰老细胞衍生的EV中的生物标志物的纳米等离子体检测，这有望满足这一需求。该项目将提供一些先进技术的培训，涵盖生物学，化学和工程学，所有这些都在转化医疗保健方面。您将开发细胞生物学技术，细胞外囊泡分离和表征，质谱和生物信息学分析和纳米等离子体检测技术的技能，沿着与患者，公众和我们的工业合作伙伴，谁将作为该项目的外部导师参与的机会。您将与化学系的博士生合作，他们将与您一起开发用于检测生物标志物的等离子体平台，作为730万英镑EPSRC资助计划的一部分。您将加入一个跨谢菲尔德大学三个学院的多学科团队，拥有长期成功的博士监督和职业发展记录。

This 3.5 year studentship is part of the Healthy Lifespan Institute (HELSI) at The University of Sheffield. HELSI is dedicated to the understanding and prevention of multimorbidity (the presence of two or more chronic health conditions that create disability and reduce quality of life). We are taking a unique multidisciplinary approach to help people live longer, healthier and more independent lives.Students within the Healthy Lifespan Institute are valued and active members of the Institute and vital in contributing to our aims and helping to effect real change. You will be part of a wider multidisciplinary network of PhD students (see here) and will have the chance to influence and lead Institute activity, seminars and events, and meeting leaders in the field. Research Project:BackgroundA recent World Health Organisation (WHO) report on healthy ageing begins: 'The world is facing a situation without precedent: We soon will have more older people than children and more people at extreme old age than ever before.' This illustrates starkly the importance of research into healthy ageing. One area of research gaining particular attention is the potential of eliminating 'zombie' cells (termed senescent cells) which accumulate with age and contribute to chronic inflammation and many diseases of ageing, using 'senotherapeutic' drugs which specifically kill senescent cells or alter their secretions.Several studies in animals using senotherapeutics have shown startling results, with increased lifespan and reduction in age-associated disease. The translation of this into humans, however, is severely impeded by the lack of non-invasive, specific, biomarkers of senescent cell load. The identification of a reliable pharmacodynamic biomarker is important, as it can be used for early assessment of a treatment effect on a potential clinical end point, including patient safety. Extracellular vesicles (EV) are small, membrane-bound structures released by cells into the surrounding environment, and are abundant in all body fluids. They contain a variety of nucleic acids, lipids and proteins, which provide a signature of the cell from which they were derived. Given the increasing understanding of the altered molecular landscape of senescent cells compared to proliferating counterparts, this raises the tantalising prospect that EVs present in body fluids may hold promise as biomarkers of senescence and that this may be exploited to develop non-invasive, low-cost assays of senescent cell load.Project aim: We propose a simple, sensitive assay based on the nanoplasmonic analysis of senescent cell-derived extracellular vesicles that could determine senescent cell load and transform the clinical translation of senotherapeutics. In this project we propose two new approaches to the detection of biomarkers of senescence based on nanoplasmonic detection of biomarkers in senescent cell-derived EV that promise to meet this need. The project will provide training in a number of advanced techniques spanning biology, chemistry and engineering, all in a translational healthcare context. You will develop skills in cell biology techniques, extracellular vesicle isolation and characterisation, mass-spectrometry and bioinformatic analyses and nanoplasmonic detection technologies, along with opportunities for engagement with patients, the public and our industrial partner, who will act as an external mentor for the project. You will work in partnership with a PhD student based in the Department of Chemistry, who will work with you to develop plasmonic platforms for use in detection of biomarkers as part of a £7.3M EPSRC-funded programme. You will join a multidisciplinary team spanning three faculties at the University of Sheffield with a long and successful track record of PhD supervision and career development.