Enzymatic tools for biotechnology and medicine

用于生物技术和医学的酶工具

• 批准号: EP/N020901/1
• 负责人: Robert Neely
• 金额: $ 127.52万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FN020901%2F1
• 关键词: Enzymatic; tools; biotechnology; medicine

The early detection and subsequent informed treatment of disease is both a significant challenge and a significant opportunity for us to improve healthcare. Sadly, diseases like cancer put a tremendous strain on the sufferer and their families and a significant burden on our laden healthcare system. Indeed, as our population continues to age the prevalence of diseases such as cancer and the need for improved diagnostics and therapies will only increase. On the other hand, there is cause for optimism as the early detection of cancer dramatically improves the outlook for sufferers. This has been clearly demonstrated by successful screening programs for breast and ovarian cancers that have had a dramatic impact on the survival rates for sufferers.One of the most promising tools in our battle to understand and identify cancer at an early stage comes in the form of small chemical modifications of our DNA, referred to as our epigenome. There is increasing evidence that the epigenome is both a critical indicator and influencer of the progression of cancer. These chemical modifications to genetic material change throughout our lives in response to many factors including ageing, the environment and disease. Our expanding knowledge in this area of research is driving the development of diagnostics that allow an individual's epigenome to be monitored as a predictive, prognostic and diagnostic marker of disease. However, epigenomic information is typically difficult and expensive to read-out and as a result there is a pressing need for the development of methodology that streamlines this process.This project will develop biochemistry, analytical and state-of-the-art imaging solutions that underpin the realization of this goal. My group will prepare combinations of small molecules (cofactors) and specially selected enzymes that can be used to track and test epigenomic modifications in our cells. Our ultimate aim is to work with medical and clinical scientists to develop and apply simple tests that will improve our ability to make informed decisions about the treatment of individual patients.

疾病的早期发现和随后的知情治疗对我们来说既是一个重大挑战，也是一个改善医疗保健的重要机会。不幸的是，像癌症这样的疾病给患者及其家人带来了巨大的压力，也给我们负担沉重的医疗保健系统带来了沉重的负担。事实上，随着我国人口继续老龄化，癌症等疾病的流行率以及对改进诊断和治疗的需求只会增加。另一方面，有理由乐观，因为癌症的早期发现大大改善了患者的前景。成功的乳腺癌和卵巢癌筛查项目已经清楚地证明了这一点，这些项目对患者的生存率产生了巨大的影响。在我们了解和识别早期癌症的斗争中，最有希望的工具之一是对我们的DNA进行小的化学修饰，称为我们的表观基因组。越来越多的证据表明，表观基因组是癌症进展的关键指标和影响因素。这些对遗传物质的化学修饰在我们的一生中会随着包括衰老、环境和疾病在内的许多因素而发生变化。我们在这一研究领域不断扩大的知识正在推动诊断学的发展，这些诊断学允许将个体的表观基因组作为疾病的预测、预后和诊断标志物进行监测。然而，表观基因组信息的读取通常是困难和昂贵的，因此迫切需要开发简化这一过程的方法。该项目将开发生物化学，分析和最先进的成像解决方案，以支持这一目标的实现。我的团队将准备小分子（辅因子）和特殊选择的酶的组合，这些酶可用于跟踪和测试我们细胞中的表观基因组修饰。我们的最终目标是与医学和临床科学家合作，开发和应用简单的测试，以提高我们对个体患者的治疗做出明智决定的能力。

项目成果

Imaging nanoscale nuclear structures with expansion microscopy.

• DOI: 10.1242/jcs.259009
• 发表时间: 2022-07-15
• 期刊: Journal of cell science
• 影响因子: 4

FRET-Based Method for Direct, Real-Time Measurement of DNA Methyltransferase Activity.

• DOI: 10.1021/acs.bioconjchem.0c00612
• 发表时间: 2020-12
• 期刊: Bioconjugate chemistry
• 影响因子: 4.7
• 作者: Yi Long;K. Ubych;E. Jagu;R. Neely

A general strategy for direct, enzyme-catalyzed conjugation of functional compounds to DNA.

• DOI: 10.1093/nar/gky184
• 发表时间: 2018-06-20
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Deen J;Wang S;Van Snick S;Leen V;Janssen K;Hofkens J;Neely RK
• 通讯作者: Neely RK

Methyltransferase-Directed Labeling of Biomolecules and its Applications.

• DOI: 10.1002/anie.201608625
• 发表时间: 2017-05-02
• 期刊: Angewandte Chemie (International ed. in English)
• 作者: Deen J;Vranken C;Leen V;Neely RK;Janssen KPF;Hofkens J
• 通讯作者: Hofkens J

Human BRCA1-BARD1 ubiquitin ligase activity counteracts chromatin barriers to DNA resection.

• DOI: 10.1038/nsmb.3236
• 发表时间: 2016-07
• 期刊: Nature structural & molecular biology
• 影响因子: 16.8
• 作者: Densham RM;Garvin AJ;Stone HR;Strachan J;Baldock RA;Daza-Martin M;Fletcher A;Blair-Reid S;Beesley J;Johal B;Pearl LH;Neely R;Keep NH;Watts FZ;Morris JR
• 通讯作者: Morris JR