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BlueCryo Image Processing Computing Cluster

BlueCryo 图像处理计算集群

基本信息

批准号：
BB/R000484/1
负责人：
Christiane Berger-Schaffitzel
金额：
$ 38.23万
依托单位：
University of Bristol
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%2FR000484%2F1
关键词：
BlueCryo Image Processing Computing Cluster

项目摘要

Imaging biomolecules at the molecular level to visualize their atomic details is essential to understand how they function in health and disease. Among the techniques capable of imaging biomolecules, electron cryo-microscopy (cryo-EM) has emerged as exceptionally powerful. New direct electron detectors, better microscopes and powerful processing software for the images recorded with this new hardware has led to a genuine revolution in cryo-EM. With these advances it is now possible to determine macromolecular structures at near-atomic resolution by cryo-EM, revealing essential molecular detail. High-resolution structural insight into molecular complexes, and also entire cells and even tissues, provide vital understanding of the molecular mechanisms of life. Until recently, high-resolution cryo-EM was not possible in the South-West due to the lack of a suitable cryo-microscope. In 2017, we answer this unmet need by opening a South West Regional Facility for High-Resolution Cryo-EM at University of Bristol, equipped with state-of-the-art hardware. This will enable us to collect several terabytes of images or movies per day of successful data collection. To fully exploit the potential of this facility, and to maintain and increase our competitive posture, we must complement the state-of-the-art cryo-microscope with equally powerful high-performance computing (HPC) for image processing. Processing of the terabytes of images is so computation-intense that existing HPC infrastructure can by no means match the computation requirements of the new EM user community.Therefore, to resolve this bottleneck, we ask here for funding of a computing cluster dedicated to image processing of cryo-EM data sets (BlueCryo). BlueCryo will enable researchers at University of Bristol to determine important structures by single particle cryo-EM and tomography, to interpret these structures using cutting-edge molecular modelling and to analyse the functional dynamics of the biological systems by state-of-the-art simulation methods. The BlueCryo HPC cluster will support the work of many researchers to accelerate their ambitious research, many of them funded by the BBSRC. The new resource will be instrumental for the discovery of new mechanisms of gene expression, to study protein transport into and across membranes, to understand the mechanism of secretion systems which play a crucial role in bacterial infections, and to illuminate a wide range of other important molecular processes responsible for biological function (and malfunction) in our cells. Moreover, the HPC cluster will critically support rational design of entirely novel proteins and peptide assemblies with tailor-made function, in vaccinology, drug delivery and drug discovery. Importantly, the new BlueCryo computing resource, together with the cryo-microscope, will further entice researchers from diverse life-science areas to partake in the cryo-EM revolution and generate new and exciting research synergies all across the South-West and beyond.Our work has broad implications for multiple areas within the BBSRC remit including synthetic biology, basic bioscience underpinning normal human and animal health and infection. The projects cover areas of direct relevance to BBSRC remit and strategy. The proposal includes researchers with a strong track record of BBSRC funding. Early career researchers and a re-entry fellow are part of our team. Clearly, the computing cluster will not only decisively advance the research here proposed, and generate new programmes, synergies and collaborations. It will also enable us to engage in many other important scientific questions and to train new users and students. Thus, we expect to derive significant additional use in many areas of basic and applied research at University of Bristol, the South-West and beyond.

在分子水平上对生物分子进行成像以可视化其原子细节对于了解它们在健康和疾病中的功能是必不可少的。在能够对生物分子成像的技术中，电子冷冻显微镜(Cryo-EM)是一种特别强大的技术。新的直接电子探测器，更好的显微镜，以及用这种新硬件记录的强大的图像处理软件，导致了低温电子显微镜的一场真正的革命。有了这些进展，现在有可能通过低温电子显微镜在近原子分辨率下确定大分子结构，揭示基本的分子细节。对分子复合体、整个细胞甚至组织的高分辨率结构洞察，提供了对生命分子机制的至关重要的理解。直到最近，由于缺乏合适的冷冻显微镜，西南地区还不可能进行高分辨率的低温电磁扫描。2017年，我们将在布里斯托尔大学开设一家配备最先进硬件的西南地区高分辨率冷冻-EM设施，以满足这一未得到满足的需求。这将使我们能够在每天成功的数据收集中收集数TB的图像或电影。为了充分利用这一设施的潜力，并保持和提高我们的竞争地位，我们必须用同样强大的用于图像处理的高性能计算(HPC)来补充最先进的冷冻显微镜。兆兆字节图像的处理是计算密集型的，现有的高性能计算基础设施根本无法满足新的EM用户群体的计算要求。因此，为了解决这一瓶颈，我们在此请求资助一个专门用于低温EM数据集图像处理的计算集群(BlueCryo)。BlueCryo将使布里斯托尔大学的研究人员能够通过单粒子冷冻-EM和断层扫描来确定重要的结构，使用尖端的分子模型来解释这些结构，并通过最先进的模拟方法分析生物系统的功能动力学。BlueCryo HPC集群将支持许多研究人员加快他们雄心勃勃的研究工作，其中许多研究是由BBSRC资助的。这一新资源将有助于发现基因表达的新机制，研究蛋白质进入和跨膜的运输，了解在细菌感染中发挥关键作用的分泌系统的机制，并阐明导致我们细胞生物功能(和故障)的广泛其他重要分子过程。此外，HPC集群将关键地支持在疫苗学、药物输送和药物发现方面具有定制功能的全新蛋白质和多肽组件的合理设计。重要的是，新的BlueCryo计算资源与低温显微镜一起，将进一步吸引来自不同生命科学领域的研究人员参与低温电磁革命，并在整个西南部和其他地区产生新的令人兴奋的研究协同效应。我们的工作对BBSRC职权范围内的多个领域具有广泛的影响，包括合成生物学、支撑正常人类和动物健康和感染的基础生物科学。这些项目涉及与BBSRC职权范围和战略直接相关的领域。该提案包括在BBSRC资助方面有良好记录的研究人员。早期职业研究人员和一名重返大气层的研究员是我们团队的一部分。显然，计算集群不仅将决定性地推进这里提出的研究，并产生新的方案、协同作用和协作。它还将使我们能够参与许多其他重要的科学问题，并培训新的用户和学生。因此，我们预计在布里斯托尔大学、西南部和其他地区的许多基础和应用研究领域将有更多的重大用途。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

CryoEM structure of the outer membrane secretin channel pIV from the f1 filamentous bacteriophage.

DOI：
10.1038/s41467-021-26610-3
发表时间：
2021-11-02
期刊：
Nature communications
影响因子：
16.6
作者：
Conners R;McLaren M;Łapińska U;Sanders K;Stone MRL;Blaskovich MAT;Pagliara S;Daum B;Rakonjac J;Gold VAM
通讯作者：
Gold VAM

In vitro generated antibodies guide thermostable ADDomer nanoparticle design for nasal vaccination and passive immunization against SARS-CoV-2

DOI：
10.1093/abt/tbad024
发表时间：
2023-11-10
期刊：
ANTIBODY THERAPEUTICS
影响因子：
0
作者：
Buzas, Dora;Bunzel, Adrian H.;Berger, Imre
通讯作者：
Berger, Imre

Cryo-electron microscopy of the f1 filamentous phage reveals insights into viral infection and assembly.

DOI：
10.1038/s41467-023-37915-w
发表时间：
2023-05-11
期刊：
NATURE COMMUNICATIONS
影响因子：
16.6
作者：
Conners, Rebecca;Leon-Quezada, Rayen Ignacia;McLaren, Mathew;Bennett, Nicholas J.;Daum, Bertram;Rakonjac, Jasna;Gold, Vicki A. M.
通讯作者：
Gold, Vicki A. M.

Zebrafish as a model for cardiac disease; Cryo-EM structure of native cardiac thin filaments from Danio Rerio.