The Next Dimension in Proteomics

蛋白质组学的新维度

• 批准号: BB/P021875/1
• 负责人: Peter O'Connor
• 金额: $ 82.34万
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FP021875%2F1
• 关键词: Next; Dimension; Proteomics

Cells, tissues, and organisms, including humans, are made of a variety of molecules, including proteins. Proteins are the 'molecular machines' responsible for everything a cell does, from replication to processing nutrients. A typical cell might have 10's of thousands of proteins doing myriad particular chemical 'jobs', including synthesizing or recycling other proteins, so the complement of proteins is constantly changing. The field of proteomics involves detecting as many of these proteins as possible, understanding how they change with time and in reaction to stress or chemical treatment. Knowing this information will allow bioscientists, from basic researchers to clinicians, to better understand what is occurring in the cell under conditions of malnutrition, disease, healthy aging, drought, or even pharmaceutical treatment. Developing better methods to measure the 'proteome' accurately and with sufficient detail is a key underpinning research goal which results in better science, better technology, and ultimately better health and healthier food. We have recently developed a new technology, called 2-dimensional mass spectrometry, which offers the capability to sequence all peptide/protein components in a sample, rather than a select few. We have demonstrated the technology works in several publications and in preliminary data on a whole proteomic analysis of yeast herein, but there are some particular challenges which we must address before the vision can be attained. This proposal aims to solve those challenges.Firstly, we will optimise our detection and fragmentation methods to increase protein sequence coverage. Secondly, we will fully characterise the technique to determine the sensitivity, resolution, accuracy, dynamic range, and capacity for quantitation and detection of protein modifications. Thirdly, we will develop a set of algorithms which will convert raw 2-dimensional MS data into protein sequence information and integrate those algorithms into a web-based data processing pipeline for automated proteomic data analysis. Finally, we will compare our newly developed 2-dimensional MS proteomic data sets with existing proteomic methodologies on the exact same set of samples, to clearly show the improvements (both delivered and potential) provided by doing proteomics with an extra dimension. The overall result of this project will be the development of protocols and methods for optimal proteomic analysis using this exciting new technology and a web-based data analysis pipeline which can process the raw 2-dimensional mass spectrometry data into protein sequence information for whole cells and tissues.

细胞，组织和生物体，包括人类，是由各种分子组成的，包括蛋白质。蛋白质是“分子机器”，负责细胞所做的一切，从复制到处理营养物质。一个典型的细胞可能有成千上万的蛋白质做无数特定的化学“工作”，包括合成或回收其他蛋白质，所以蛋白质的补充是不断变化的。蛋白质组学领域涉及检测尽可能多的这些蛋白质，了解它们如何随时间变化以及对压力或化学处理的反应。了解这些信息将使从基础研究人员到临床医生的生物科学家能够更好地了解在营养不良，疾病，健康衰老，干旱甚至药物治疗的条件下细胞中发生的事情。开发更好的方法来准确和足够详细地测量“蛋白质组”是一个关键的基础研究目标，这将导致更好的科学，更好的技术，最终更好的健康和更健康的食品。我们最近开发了一种称为二维质谱的新技术，它提供了对样品中所有肽/蛋白质组分进行测序的能力，而不是选择少数几种。我们已经在几个出版物和本文酵母的整个蛋白质组学分析的初步数据中证明了该技术的工作，但在实现愿景之前，我们必须解决一些特殊的挑战。该提案旨在解决这些挑战。首先，我们将优化我们的检测和片段化方法，以增加蛋白质序列覆盖率。其次，我们将充分验证该技术，以确定灵敏度、分辨率、准确度、动态范围以及定量和检测蛋白质修饰的能力。第三，我们将开发一套算法，将原始二维MS数据转换为蛋白质序列信息，并将这些算法集成到基于Web的数据处理管道中，用于自动化蛋白质组数据分析。最后，我们将比较我们新开发的二维MS蛋白质组数据集与现有的蛋白质组学方法在完全相同的样本集，以清楚地显示改进（交付和潜力）通过做蛋白质组学与额外的维度。该项目的总体结果将是使用这种令人兴奋的新技术和基于网络的数据分析管道开发最佳蛋白质组学分析的协议和方法，该数据分析管道可以将原始二维质谱数据处理为整个细胞和组织的蛋白质序列信息。

项目成果

Investigating the Influence of n-Heptane versus n-Nonane upon the Extraction of Asphaltenes.

• DOI: 10.1021/acs.energyfuels.2c01168
• 发表时间: 2022-08-18
• 期刊: ENERGY & FUELS
• 影响因子: 5.3
• 作者: Alostad, Latifa K.;Lozano, Diana Catalina Palacio;Gannon, Benedict;Downham, Rory P.;Jones, Hugh E.;Barrow, Mark P.
• 通讯作者: Barrow, Mark P.

Generation of maghemite nanocrystals from iron-sulfur centres.

从铁硫中心生成磁赤铁矿纳米晶体。

• DOI: 10.1039/c9dt00514e
• 发表时间: 2019
• 期刊: 2003)
• 作者: Banerjee S

New activation mechanism for half-sandwich organometallic anticancer complexes.

• DOI: 10.1039/c7sc05058e
• 发表时间: 2018-03-28
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Banerjee S;Soldevila-Barreda JJ;Wolny JA;Wootton CA;Habtemariam A;Romero-Canelón I;Chen F;Clarkson GJ;Prokes I;Song L;O'Connor PB;Schünemann V;Sadler PJ
• 通讯作者: Sadler PJ

Label-Free Nanoimaging of Neuromelanin in the Brain by Soft X-ray Spectromicroscopy

通过软 X 射线光谱显微镜对大脑中的神经黑色素进行无标记纳米成像

• DOI: 10.1002/ange.202000239
• 发表时间: 2020
• 期刊: Angewandte Chemie
• 作者: Brooks J

Multiple Protective Roles of Nanoliposome-Incorporated Baicalein against Alpha-Synuclein Aggregates

• DOI: 10.1002/adfm.202007765
• 发表时间: 2020-11-18
• 期刊: ADVANCED FUNCTIONAL MATERIALS
• 影响因子: 19
• 作者: Aliakbari, Farhang;Mohammad-Beigi, Hossein;Otzen, Daniel E.
• 通讯作者: Otzen, Daniel E.