Novel nanoplasmonic sensors for non-invasive detection of senescence

这项为期3.5年的学习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发性疾病(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、更健康和更独立。健康寿命研究所的学生是该研究所宝贵和积极的成员，对促进我们的目标和帮助实现真正的变化至关重要。你将成为更广泛的多学科博士生网络的一部分(见这里)，并将有机会影响和领导研究所的活动、研讨会和活动，并会见该领域的领导人。研究项目：背景世界卫生组织(WHO)最近发布的一份关于健康老龄化的报告开头写道：世界正面临着一种前所未有的局面：我们很快就会有比儿童更多的老年人，比以往任何时候都更多的极老年人口。这鲜明地说明了研究健康老龄化的重要性。一个受到特别关注的研究领域是，使用专门杀死衰老细胞或改变其分泌的“衰老”药物，消除随年龄积累的“僵尸”细胞(称为衰老细胞)的潜力，这些细胞会导致慢性炎症和许多老年性疾病。在动物身上进行的几项使用衰老疗法的研究显示了惊人的结果，延长了寿命，减少了与年龄相关的疾病。然而，由于缺乏衰老细胞负荷的非侵入性、特异性和生物标记物，这种基因在人体内的翻译受到严重阻碍。确定可靠的药效学生物标志物很重要，因为它可以用于对潜在临床终点的治疗效果的早期评估，包括患者的安全性。细胞外小泡(EV)是细胞释放到周围环境中的小的、膜结合的结构，在所有体液中都有丰富的存在。它们含有各种核酸、脂类和蛋白质，它们提供了它们来源细胞的特征。鉴于对衰老细胞与增殖细胞相比，衰老细胞分子格局变化的了解越来越多，这提出了诱人的前景，即存在于体液中的EVS可能有望作为衰老的生物标记物，这可能被利用来开发非侵入性的、低成本的衰老细胞负荷分析。项目目标：我们提出一种简单、敏感的分析方法，该方法基于对衰老细胞来源的细胞外小泡的纳米等离子分析，可以确定衰老细胞负荷并改变老年治疗药物的临床翻译。在这个项目中，我们提出了两种新的检测衰老生物标志物的方法，这两种方法基于对衰老细胞来源的电动汽车中生物标志物的纳米等离子检测，有望满足这一需求。该项目将提供横跨生物、化学和工程的一些先进技术方面的培训，所有这些都是在转化性医疗保健的背景下进行的。您将在细胞生物学技术、细胞外囊泡分离和表征、质谱学和生物信息学分析以及纳米等离子检测技术方面发展技能，以及与患者、公众和我们的工业合作伙伴接触的机会，后者将作为该项目的外部导师。你将与化学系的一名博士生合作，作为GB 730万EPSRC资助项目的一部分，他将与你合作开发用于生物标志物检测的血浆平台。你将加入谢菲尔德大学一个由三个学院组成的多学科团队，在博士指导和职业发展方面有着长期和成功的记录。

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.